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Objectives: To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT)., Methods: Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking., Results: In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks., Conclusions: Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice., Trial Registration Number: EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815., Competing Interests: Competing interests: LP reports institutional support for the present manuscript from Amsterdam University Medical Centers. MLH reports institutional grants from AbbVie, Bristol Myers Squibb, Eli Lilly, MSD, Pfizer, Sandoz, Novartis, Nordforsk and UCB; speaker honoraria from Medac, Novartis, Pfizer, Sandoz and UCB; institutional data safety monitoring board or advisory board fees from AbbVie. MLH has chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary data and is partly funded by Novartis and UCB. DCN reports research grant from MSD; consulting fees from Bristol Myers Squibb, Lilly, Novartis, Pfizer, and UCB; speaker honoraria from Pfizer and UCB; participation on a data safety monitoring board or advisory board fees from UCB. MØ reports institutional grants from AbbVie, Amgen, Bristol Myers Squibb, Merck, Celgene, Eli Lilly Novartis and UCB; personal speaker honoraria from AbbVie, Bristol Myers Squibb, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB; participation on a data safety monitoring board or advisory board personal fees from AbbVie, Bristol Myers Squibb, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB. EAH reports institutional grant from research council of Norway; personal speaker honoraria from Pfizer, UCB and Novartis; and participation on a data safety monitoring board or advisory board fees from AbbVie, Pfizer and Eli Lilly. TU reports personal speaker honoraria from Lilly, Pfizer, UCB and Galapagos. TR reports a patent application (TR is the inventor) based on the use of bioengineered IgG targets for the characterisation of rheumatoid factor reactivity patterns. RFvV reports institutional support for the present manuscript from Bristol Myers Squibb; institutional grants for research or education from Alfasigma, AstraZeneca, Bristol Myers Squibb, Galapagos, MSD, Novartis, Pfizer, Roche, Sanofi and UCB; consulting fees from AbbVie, AstraZeneca, Biogen, Bristol Myers Squibb, Galapagos, GSK, Janssen, Pfizer, RemeGen and UCB; speaker honoraria from AbbVie, AstraZeneca, Bristol Myers Squibb, Galapagos, GSK, Janssen, Pfizer and UCB; and participation on a data safety monitoring board or advisory board fees from AbbVie, AstraZeneca, Biogen, Bristol Myers Squibb, Galapagos, GSK, Janssen, Pfizer, RemeGen and UCB. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objective: The high prevalence of osteoporosis in rheumatoid arthritis (RA) is due to inflammation that stimulates differentiation of osteoclasts, a process involving circulating monocytes and T cell-derived factors. The aim of this study was to evaluate relations between circulating monocytes, T cell subsets, and changes in bone characteristics before and after treatment with biological disease-modifying antirheumatic drugs (bDMARDs) in RA., Methods: Thirty patients with untreated early RA who met the American College of Rheumatology/EULAR 2010 criteria were included. Data were collected before and 48 weeks after treatment with methotrexate (MTX) together with one of three bDMARDs (abatacept, tocilizumab, or certolizumab pegol). Disease activity was measured using the Clinical Disease Activity Index, swollen or tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates. Proportions of monocyte and CD4 + T cell subsets in blood samples were analyzed by flow cytometry. Bone densitometry was performed using high-resolution peripheral quantitative computed tomography (HR-pQCT)., Results: HR-pQCT revealed an overall decrease in cortical (P = 0.009) and trabecular (P = 0.034) bone mineral density, although a subset of patients showed no bone loss after 48 weeks of treatment. The overall bone loss was not associated with age, body mass index, sex, intraarticular glucocorticoid injections, or baseline disease activity. Loss of trabecular bone volume fraction correlated with high proportions of circulating CXCR3 + Th2 cells (r = -0.38, P = 0.04) and CXCR3 + Th17 cells (r = -0.36, P = 0.05) at baseline. Similarly, no loss of trabecular bone volume fraction correlated with high proportions of regulatory T cells (r = 0.4, P = 0.03) at baseline. However, the associations were not significant when corrected for confounders and multiple testing., Conclusion: MTX together with bDMARDs efficiently reduce disease activity but only prevent bone loss in a subset of patients with RA after 48 weeks of treatment. The correlations of circulating baseline T helper cell and regulatory T cell populations with trabecular bone changes suggest a potential novel role for these cells in systemic bone homeostasis during early RA., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Current risk algorithms do not accurately predict cardiovascular disease (CVD) risk in rheumatoid arthritis (RA). An area of interest is that of single-nucleotide polymorphisms (SNPs), of which several have been associated with CVD in the general population. We investigated whether these SNPs are associated with CVD in RA and whether SNPs could improve CVD risk prediction in RA., Methods: Sixty SNPs were genotyped in 353 patients with RA. Logistic and Cox regression analyses were performed to identify SNPs that were associated with CVD (n = 99). A prediction model with clinical variables was made. SNPs were added to investigate the additional predictive value. Both models were internally validated. External validation was done in a separate cohort (n = 297)., Results: rs3184504, rs4773144, rs12190287, and rs445925 were significantly associated with new CVD. The clinical prediction model consisted of age, sex, body mass index, systolic blood pressure, high-density lipoprotein cholesterol (HDLc), and creatinine, with an area under the curve (AUC) of 0.74 (P = 0.03). Internal validation resulted in an AUC of 0.76 (P < 0.01). A new model was made including SNPs and resulted in a model with rs17011666 and rs801426, age, total cholesterol, and HDLc, which performed slightly better with an AUC of 0.77 (P < 0.01). External validation resulted in a good fit for the clinical model, but a poor fit for the SNP model., Conclusion: Several SNPs were associated with CVD in RA. Risk prediction slightly improved after adding SNPs to the models, but the clinical relevance is debatable. However, larger studies are needed to determine more accurately the additional value of these SNPs to CVD risk prediction algorithms., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: To investigate sex differences in patient-reported outcome measures (PROMs) among axSpA patients initiating their first TNFi and identify factors contributing to these disparities over the follow-up., Methods: Data were included from 15 EuroSpA registries and consisted of axSpA patients initiating their first TNFi, with ≥2 measurements for each analysed PROM (BASDAI and BASFI, scale 0-100) taken at any time point. Linear mixed models were employed to analyse sex differences in PROMs over 24 months and to evaluate how baseline characteristics were related to the observed sex differences., Results: We analysed 13 102 (38% women) in the BASDAI analyses and 10 623 (38% women) in the BASFI analyses. At follow-up, mean sex differences in BASDAI increased from 4.3 units at baseline (95% CI, 3.5-5.1)-8.0 (7.2-8.8) at 6 months, and in BASFI from 2.2 (1.4-3.1)-4.6 (3.6-5.5), with consistently worse scores in women. Baseline characteristics could not substantially account for the observed sex differences over time; however, the magnitude of the sex differences was reduced by HLA-B27 positivity, longer disease duration, and increased CRP levels, but increased by TNFi initiation in later years and peripheral arthritis., Conclusion: In axSpA patients initiating their first TNFi, baseline sex differences in BASDAI and BASFI increased two-fold after 6 months of treatment and persisted thereafter, with worse scores in women. Several baseline characteristics moderated the sex differences, though none could fully account for them. These findings improve our understanding of sex differences and underscore their importance in axSpA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The aim of the current study was to explore the changes in lipid and NT-proBNP levels in rheumatoid arthritis (RA) patients through different phases of the disease: from the pre-clinical stage and RA onset up to the treatment phase with biological disease-modifying anti-rheumatic drugs (bDMARDS)., Methods: Thirty-eight consecutive patients, initially with arthralgia and rheumatoid factor and/or anti-citrullinated protein antibodies without arthritis, who later developed RA and eventually started treatment with bDMARDs, were included. Lipid spectrum and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured longitudinally from several months before diagnosis through treatment with bDMARDs., Results: From baseline, C-reactive protein (CPR) initially increased sharply, decreasing with the start of biological treatment. Low-density lipoprotein-cholesterol (LDL-c) remained stable, high-density lipoprotein-cholesterol (HDL-c) increased, apolipoprotein A1 (ApoA1 and lipoprotein (a) (Lp(a)), and total cholesterol (TC)/HDL-c ratio and apolipoprotein B (ApoB) decreased during follow-up. NT-proBNP closely followed progression of CRP. TC, LDL-c, TC/HDL-c ratio, ApoA and ApoB inverse correlated with CRP, while Lp(a) positively correlated. HDL-c and triglycerides showed no correlation., Conclusion: Changes in the lipid profile and NT-proBNP in RA patients seem to be related to inflammation, with changes reflecting an increase in CVD risk occurring along with rises in CRP levels. These changes seem to already be present at diagnosis, indicating the need for timely control of inflammation., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: During the COVID-19 pandemic, we developed a digital research platform to longitudinally investigate COVID-19-related outcomes in patients with rheumatic diseases and healthy controls. We used home finger-prick testing in order to collect serum samples remotely and increase the overall efficiency of the platform. The aim of the present study was to evaluate the success rate of the finger prick and patients' perspective towards the finger prick., Methods: Serum samples were collected up to five times during follow-up, either via a venepuncture at the research institute or a finger prick from participants' home. Participants were asked to complete a digital evaluation questionnaire of the finger prick after their attempts., Results: A total of 2135 patients and 899 controls performed at least one finger prick and were included in this study. The first finger prick was successfully done by 92% (95% CI: 90% to 93%) of patients, 94% (95% CI: 92% to 95%) of controls, 93% (95% CI: 92% to 94%) of all participants aged ≤70 years and 89% (95% CI: 86% to 92%) of all participants aged >70 years. Sex did not impact these success rates. Repeated failure occurred in 11/439 (0.8%) patients and 4/712 (0.6%) controls. Both patients and controls were less willing to perform a finger prick for individual healthcare compared with scientific research., Conclusion: The vast majority of participants, among which elderly and patients with rheumatic diseases, were able to successfully draw the required amount of blood for serological analyses. This shows that finger-prick testing is suitable for a high-throughput implementation to monitor patients remotely., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early rheumatoid arthritis (RA)., Methods: This report included 793 participants with untreated early RA from the randomised, longitudinal NORD-STAR trial, all of whom had their body mass index (BMI) assessed at baseline. Obesity was defined as BMI ≥30 kg/m 2 . All participants were randomised 1:1:1:1 to one of four treatment arms: active conventional treatment, certolizumab-pegol, abatacept and tocilizumab. Clinical and laboratory measurements were performed at baseline and at 8, 12, 24 and 48-week follow-up. The primary endpoint for this report was response to treatment based on Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) remission and Disease Activity Score with 28 joints using C-reactive protein (DAS28-CRP) <2.6 stratified by BMI., Results: Out of 793 people included in the present report, 161 (20%) had obesity at baseline. During follow-up, participants with baseline obesity had higher disease activity compared with those with lower BMI, despite having similar disease activity at baseline. In survival analyses, obesity was associated with a lower likelihood of achieving response to treatment during follow-up for up to 48 weeks (CDAI remission, HR 0.84, 95% CI 0.67 to 1.05; SDAI, HR 0.77, 95% CI 0.62 to 0.97; DAS28-CRP <2.6, HR 0.78, 95% CI 0.64 to 0.95). The effect of obesity on response to treatment was not influenced by the treatment arms., Conclusion: In people with untreated early RA followed up for up to 48 weeks, obesity was associated with a lower likelihood of good treatment response, irrespective of the type of randomised treatment received., Trial Registration Number: NCT01491815., Competing Interests: Competing interests: MLH reports research grants from AbbVie, iogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V., Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordforsk to institution; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Medac, Sandoz paid to institution; participation on a Data Safety Monitoring Board or Advisory Board from AbbVie paid to institution; MLH has chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies; MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylarthritis based on secondary data and is partly funded by Novartis. DN reports personal consultancy fees from BMS, Lilly, MSD, Novartis, Pfizer and UCB, and personal study grant from MSD, outside current work. BG reports consulting fee from Novartis and Lectures fees from Novartis and Nordic Pharma. MØ reports grants from Amgen, BMS, Merck, Celgene and Novartis to institution; consulting fees from Galapagos, Gilead, Hospira, Janssen, Merck, Novartis, Pfizer, UCB; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, BMS, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, UCB; support for attending meetings and/or travel from UCB; participation on a Data Safety Monitoring Board or Advisory Board from Galapagos, Gilead, Hospira, Janssen, Merck, Novartis, Pfizer, UCB. TS-I reports research grant from Amgen paid to the institution, honoraria from Nordic Pharma. TU reports personal fees from Galapagos, Lilly, Pfizer, UCB outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Aims: Methotrexate (MTX) is the cornerstone in the treatment of rheumatoid arthritis (RA) patients. However, adherence to MTX therapy is not optimal, and instruments to assess medication nonadherence are warranted. To date there is no consensus on the best method to determine adherence to MTX. The aim of this study was to assess the correlation between adherence assessed with a Medication Event Monitoring System (MEMS) vs. pill count, MTX-polyglutamate (PG) concentration and Compliance Questionnaire-Rheumatology (CQR) in patients with established RA. Second, the correlations between these methods and the Disease Activity Scores of 28 joints (DAS28) were examined., Methods: Adult RA patients currently treated with MTX were included. Multivariable linear and logistic regression were used, with adherence assessed with MEMS as dependent variable vs. pill count, MTX-PG concentrations, CQR as independent variables and DAS28 vs. each of the 4 adherence measurements. Covariates were included, such as comedication, age and use of corticosteroids., Results: In total, 190 consecutive RA patients were included. Pill count was correlated with adherence assessed with MEMS (linear regression, β = 0.588, 95% confidence interval = 0.255-0.921, P < .001), whereas CQR and MTX-PGs were not. Logistic regression confirmed the correlation between dichotomized adherence and pill count only (β = 4.47, 95% confidence interval = 1.31-7.64, P =  .006). No other correlations were found, either for all adherence outcomes or DAS28., Conclusion: Measuring adherence with MEMS is correlated with pill count, whereas other methods were not correlated with MEMS or with DAS28. Pill count can be used to estimate adherence to MTX therapy, in case MEMS is not achievable., (© 2023 British Pharmacological Society.)

Purpose: This review aims to critically evaluate the potential benefit of either oral or subcutaneous administration of methotrexate (MTX) in various immune-mediated inflammatory disorders (IMIDs) through analysis of efficacy, toxicity, pharmacokinetics and pharmacodynamics of both administration routes., Recent Findings: Recent studies comparing the efficacy of oral versus subcutaneous MTX administration in IMIDs have revealed contradicting results. Some reported higher efficacy with subcutaneous administration, while others found no significant difference. Regarding toxicity, some studies have challenged the notion that subcutaneous administration is better tolerated than oral administration, while others have supported this. Pharmacokinetic studies suggest higher plasma bioavailability and increased accumulation of MTX-polyglutamates (MTX-PGs) in red blood cells (RBCs) with subcutaneous administration during the initial treatment phase. However, after several months, similar intracellular drug levels are observed with both administration routes. There is no conclusive evidence supporting the superiority of either oral or subcutaneous MTX administration in terms of efficacy and adverse events in IMIDs. Subcutaneous administration leads to higher plasma bioavailability and initial accumulation of MTX-PGs in RBCs, but the difference seems to disappear over time. Given the variable findings, the choice of administration route may be based on shared decision-making, offering patients the option of either oral or subcutaneous administration of MTX based on individual preferences and tolerability. Further research is needed to better understand the impact of MTX-PGs in various blood cells and TDM on treatment response and adherence to MTX therapy., (© 2023. The Author(s).)

Objectives: This study aims to assess current cardiovascular disease risk and prevalence of risk factors in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (SpA)., Methods: 2050 consecutive patients with inflammatory arthritis (IA) and 939 controls were included, with 1308 patients with RA, 356 patients with PsA and 386 patients with SpA. In a prospective cohort setting, questionnaires regarding previous cardiovascular events and risk factors were used to assess cardiovascular risk and prevalence in patients with IA by calculating ORs using logistic regression models., Results: 'Traditional' cardiovascular (CV) risk factors were significantly elevated in patients with IA compared with controls. Cardiovascular disease (CVD) ORs were increased in patients with RA and PsA compared with controls, 1.61 (95% CI: 1.04 to 2.48) and 2.12 (95% CI: 1.23 to 3.66), respectively, and a trend towards increased odds was observed in patients with SpA (OR 1.43; 95% CI: 0.79 to 2.59). After adjusting for traditional risk factors, CV risk was not increased in patients with RA (OR; 0.95, 95% CI: 0.58 to 1.55), PsA (OR 1.19; 95% CI: 0.64 to 2.22) and SpA (OR; 0.91, 95% CI: 0.47 to 1.77)., Conclusion: CVD is currently still more prevalent in patients with IA compared with healthy controls and, more importantly, this elevated risk is highly influenced by an increased prevalence of 'traditional' CV risk factors. More attention to, as well as improvements in, identification and treatment of 'traditional' risk factors, need to be made for not only RA, but other IA conditions as well., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Self-monitoring and patient-initiated care (PIC) leads to fewer outpatient clinic visits in patients with established RA with low disease activity (LDA) while healthcare outcomes are similar. This study assesses the cost-effectiveness of PIC with self-monitoring., Methods: A 12-month randomized controlled trial was performed with 49 patients in the PIC with self-monitoring group (app-group) and 53 in usual care. The usual care group continued with preplanned visits. The app group had one planned follow-up visit after 12 months and monitored their RA disease activity in a smartphone app. Both groups could make additional appointments at liberty. We included adult RA patients with a disease duration of over 2 years, a disease activity score 28 (DAS28) below 3.2 that were stable on medication for at least 6 months. The effect measure, the DAS28, was measured at 12 months and healthcare resource usage and productivity losses were measured at 3, 6, 9 and 12 months., Results: There was no significant difference in mean change of DAS28 (-0.04 mean difference, 95% CI: -0.39, 0.30), nor a statistically significant difference in total costs (mean difference €514, 95% CI:-€266, €3690) in the app group compared with the usual care group. The probability that the app was cost-effective was 0.37 and 0.57 at a willingness-to-pay threshold of 0 and 50 000 €/point improvement DAS28, respectively., Conclusion: Although rheumatic care costs were significantly lower in the app group, total costs and effects of PIC with self-monitoring were not different from usual care in RA patients with LDA., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action., Methods: Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025)., Results: Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%., Conclusions: Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments., Trial Registration Number: NCT01491815., Competing Interests: Competing interests: MØ received the study drug from BMS and UCB; research grants from Abbvie, BMS, Merck, Novartis and UCB; speaker fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, and UCB; and consultancy fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz and UCB. RFvV received the study drug from BMS and UCB; research grants from BMS, GSK, UCB and AstraZeneca; consulting fees from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer and UCB; expert fees from AbbVie, Galapagos, GSK, Janssen, Pfizer, R-Pharma and UCB; and advisory board fees from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer and UCB. MLH received research grants from AbbVie, Biogen, BMS, Celtrion, Eli Lily, Janssen Biologics B.V., Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz and Novartis; and institution pay from Pfizer, Medac, AbbVie and Sandoz; chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies; cochairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis. DCN received consulting fees from AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB' meeting support from Pfizer; advisory board participation fee from Novartis; and other service fee by BMS. MTN received research grants from AbbVie, BMS, Pfizer, Galapagos, Amgen and Eli Lily. BG received consulting fee from Novartis and honorary lecture payment from Novartis and Nordic-Pharma. IG received royalty fee for book authorship and support for attending meetings by EULAR. DG received advisory board fee from Eli Lily and AbbVie and speakers fee from Eli Lily. A-BA received speakers fee from AbbVie, Eli Lily, Novartis and Pfizer. CG received the study drug from BMS and UCB. MKL received advisory board fee from AbbVie. AS received advisory board fee from GSK (institution pay). LU received speakers fee from Janssen and support for meeting/travel from AbbVie and Eli Lily. DJS received honorarium fee from UCB (not a part of this, unrelated medication). GB received consultancy fee from UCB. ICO received research grants from EU Horizon 2020 and EU Horizon Europe, advisory board participation from IMPRESS-Norway, ALPHA2PREVENT, FLECAPRO and EVOLVD, and meeting/travel support from European Clinical Research Infrastructure Network. The remaining authors declared no disclosures., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To study changes in retention of first biologic disease-modifying antirheumatic drug (DMARD) therapy over a period of 15 years in an inception cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS)., Methods: We assessed patient and disease characteristics and drug survival of patients starting a biologic (tumor necrosis factor inhibitor [TNFi]) therapy between 2004 and 2019 in routine care at the Amsterdam Rheumatology and Immunology Center, Reade, the Netherlands. Starts were classified as early (2004-2008), intermediate (2009-2013), and recent (2014-2018). Kaplan-Meier plots and log-rank tests assessed the overall difference in drug survival between the 3 observation groups and between diagnoses, followed by Cox regression to estimate hazard ratios (HRs)., Results: We included 1938 consecutive patients starting TNFi therapy, 63% with RA, 19% with PsA, and 19% with AS; 65% were female. Drug survival decreased significantly over time (overall P < 0.001), mostly caused by decreases in the most recent 4-year period. The HR for drug continuation was 2.04 (95% CI 1.71-2.43, P < 0.001) for the early vs the recent group and 1.92 (95% CI 1.58-2.35, P < 0.001) for the intermediate vs the recent group. Drug survival time was significantly different between diseases (overall P < 0.001), mostly caused by shorter survival in RA. The HR for drug continuation was 0.58 (95% CI 0.47-0.73, P < 0.001) for RA vs PsA and 0.63 (95% CI 0.51-0.78, P < 0.001) for RA vs AS., Conclusion: Patients with RA, PsA, and AS currently initiating biologic (TNFi) therapy discontinue the drug much sooner than those starting shortly after the drugs were introduced. This is most likely because of the availability of alternative novel biologic and targeted synthetic DMARD treatments and treat-to-target protocols enabling and necessitating earlier switching.

Objectives: To estimate the 10-year cardiovascular disease (CVD) risk in gout patients in secondary care and to evaluate the effect of CVD risk screening on the 10-year CVD risk after 1 year., Methods: A prospective cohort study was performed in patients with gout from Reade Amsterdam. Data on gout and CVD history, traditional risk factors, medication, and lifestyle were collected at baseline and 1 year. The 10-year CVD risk was calculated with the use of the NL-SCORE. A paired sample t-test and McNemar test was performed to test for differences between baseline and the 1-year visit., Results: A very high prevalence of traditional CV risk factors was seen in our secondary care gout patients. Nineteen percent without previous CVD were categorised in the high-risk group according the NL-SCORE. The prevalence of CVD increased from 16% to 21% after 1-year follow-up. A decrease was seen in total- and LDL-cholesterol after 1 year. No decrease in mean BMI, waist-hip ratio, blood pressure or NL-SCORE was observed., Conclusions: The current need for CVD risk screening of gout patients in secondary care was illustrated by the high prevalence of traditional risk factors in this cohort. Recommendations to patients and the general practitioner (GP) alone did not result in overall improvement of traditional CVD risk factors nor the 10-year CVD risk. Our results indicate that a more prominent role of the rheumatologist is necessary to optimise the process of initiation and management of CVD risk in gout patients.

Background: Fatigue is a common problem in immune-mediated inflammatory disease (IMID) patients, significantly impacting their quality of life., Objectives: In this study, we describe the pattern and characteristics of fatigue as a patient-reported adverse drug reaction (ADR) of biologics, and compared patient and treatment characteristics with patients reporting other ADRs or no ADRs., Methods: In this cohort event monitoring study, the description and characteristics of fatigue reported as a possible ADR in the Dutch Biologic Monitor were assessed and analysed for commonly recurring themes or patterns. Baseline and treatment characteristics of patients with fatigue and patients reporting other ADRs or no ADRs were compared., Results: Of 1382 participating patients, 108 patients (8%) reported fatigue as an ADR of a biologic. Almost half of these patients (50 patients, 46%) described episodes of fatigue during or shortly after biologic injection, which often recurred following subsequent injections. Patients with fatigue were significantly younger than patients with other ADRs or patients without ADRs (median age for patients with fatigue, 52 years; median age for patients with other ADRs, 56 years; and median age for patients without ADRs, 58 years); significantly more often smoked (25% vs. 16% and 15%); used infliximab (22% vs. 9% and 13%), rituximab (9% vs. 3% and 1%) or vedolizumab (6% vs. 2% and 1%); and significantly more often had Crohn's disease (28% vs. 13% and 13%) and other comorbidities (31% vs. 20% and 15%). Patients with fatigue significantly less frequently used etanercept (12% vs. 29% and 34%) or had rheumatoid arthritis (30% vs. 45% and 43%)., Conclusions: IMID patients may experience fatigue as a postdosing effect of biologics., (© 2023. The Author(s).)

Background: To evaluate the real-world effect of the IL-12/23 inhibitor ustekinumab or of a tumour necrosis factor inhibitor (TNFi) on patient-reported outcomes (PRO) and their association with effectiveness endpoints in psoriatic arthritis (PsA) patients over 3 years., Methods: In PsABio (NCT02627768), a prospective, observational study, patients with PsA that were prescribed first- to third-line ustekinumab or a TNFi, and remained on that drug for 3 years, were analysed for change in baseline in PROs (EuroQol-5 dimensions health state VAS [EQ-5D VAS], 12-item Psoriatic Arthritis Impact of Disease questionnaire [PsAID-12; range 0-10], Work Productivity and Activity Impairment for Psoriatic Arthritis questionnaire [WPAI; results expressed as a percentage for each domain]), and the association between PROs and WPAI with effectiveness endpoints, clinical disease activity index for psoriatic arthritis (cDAPSA), low disease activity (LDA)/remission, minimal disease activity (MDA) and very low disease activity (VLDA)., Results: In 437 patients (mean age 49.1 years, 47.8% female), at 3 years, ustekinumab and TNFi treatment led to comparable improvements in EQ-5D VAS; mean change from baseline (95% confidence intervals [CI]) was 11.0 (6.5; 15.4) and 18.9 (14.0; 23.9), respectively. Both groups improved PsAID-12 after 3 years; mean change from baseline (95% CI) was -2.9 (-3.2; -2.5) and -3.5 (-3.9; -3.2), respectively. At baseline, due to their PsA, TNFi-treated patients had lower work productivity compared to ustekinumab-treated patients; mean productivity reduction (95% CI) was 58.8 [52.4; 65.2] and 43.3 [35.6; 51.1]. Over 3 years, TNFi-treated patients had a greater improvement in work productivity compared to ustekinumab-treated patients, ultimately leaving work productivity to be comparable between groups; mean improvement (95% CI) was 44.5% (38.4; 50.6) and 24.9% (15.8; 34.0), respectively. A similar trend was observed in activity impairment. Patients in both treatment groups who achieved effectiveness endpoints, cDAPSA LDA/remission, MDA, and VLDA had greater improvement in PROs and WPAI than patients who did not achieve these endpoints., Conclusions: At 3 years, improvements in PROs following ustekinumab or TNFi treatment were generally comparable; however, TNFi-treated patients achieved a greater improvement in work productivity, although this group started from a lower baseline. Achievement of effectiveness endpoints, independent of treatment group, also improved PROs., Trial Registration: ClinicalTrials.gov, NCT02627768. Registered on 11 December 2015., (© 2023. The Author(s).)

Background: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway., Methods: A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document., Results: The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, Castleman's disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring., Conclusions: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers., Competing Interests: Competing interests: DA: Grants or contracts from any entity: AbbVie, Amgen, Eli Lilly, Novartis, Roche, SoBi and Sanofi; Consulting fees: AbbVie, Amgen, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche and Sandoz; Support for attending meetings and/or travel: AbbVie, Gilead, Sandoz, Pfizer, BMSAK: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, Bristol-Myers Squibb, Celgene, Eli-Lilly, Gilead, Janssen, Merck Sharp and Dohme, Novartis and PfizerKK: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Boehringer Ingelheim, UCB Pharma and AbbVie; Support for attending meetings and/or travel: AbbVie, Gilead, Sandoz, Pfizer and BMSJI: Grants or contracts from any entity: Pfizer, GSK and Janssen; Consulting fees: AbbVie, Gilead and BMS; Payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events: AbbVie, Gilead and Roche; Support for attending meetings and/or travel: Eli Lilly and Gilead; Participation on a Data Safety Monitoring Board or Advisory Board: Eli Lilly; Leadership or fiduciary role in other board, society, committee or advocacy group: Versus Arthritis Board member (unpaid) NS: Grants or contracts from any entity: AstraZeneca, Boehringer Ingelheim, Novartis and Roche Diagnostics; Consulting fees: Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, MSD, Novartis, Novo Nordisk, Pfizer and SanofiMV: Grants or contracts from any entity: PfizerBC: Grants or contracts from any entity: Pfizer, Roche, Chugai and Novartis; Consulting fees: AbbVie, Celltrion, Janssen, Gilead-Galapagos, Eli Lilly, Novartis, Roche-Chugai; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, BMS, Celltrion, Gilead-Galapagos, Janssen, Eli Lilly, Merck, Pfizer and Roche-ChugaiNB: All support for the present manuscript: Vienna Medical Academy; Consulting fees: Amgen, EULAR, Galapagos, Global Alliance for Patient Access, Grunenthal, Eli Lilly, Pfizer and Sanofi; Support for attending meetings and/or travel: EULAR and Global Alliance for Patient Access; Receipt of equipment, materials, drugs, medical writing, gifts or other services: GalapagosJB: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Eli Lilly and Galapagos; Participation on a Data Safety Monitoring Board or Advisory Board: SyneosGRB: All support for the present manuscript: Sanofi; Consulting fees: AbbVie, Galapagos, Lilly, Pfizer, Roche and Sanofi; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, Galapagos, Lilly, Pfizer, Roche and SanofiVPB: Grants or contracts from any entity: NIH (NIAID/NIAMS), The Cedar Hill Foundation, Amgen and BMS; Consulting fees: Amgen, BMS, Genzyme, Gilead, Janssen, Pfizer and Sanofi-Aventis; Participation on a Data Safety Monitoring Board or Advisory Board: KAI for NIHRC: noneEC: Grants or contracts from any entity: Bio-Cancer, Biogen, Novartis, Pfizer and Sanofi; Consulting fees: AbbVie, Amgen, BMS, Biocon, Eli Lilly, Galapagos, Chugai Pharma, Janssen, Novartis, Pfizer, Regeneron, Roche, Sanofi and RPharm; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, Amgen, BMS, Chugai Pharma, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Regeneron, Roche, RPharm and Sanofi; Support for attending meetings and/or travel: Gilead, Galapagos, AbbVie and Eli LillyMT: Grants or contracts from any entity: Albireo, Cymabay, Falk, Gilead, Intercept, MSD, Takeda, Alnylam and Ultragenyx; Consulting fees: Albireo, BioMX, Boehringer Ingelheim, Falk, Genfit, Intercept, Janssen, MSD, Gilead, Novartis, Shire, Phenex and Regulus; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Falk Foundation, Gilead, Intercept and MSD; Support for attending meetings and/or travel: AbbVie, Falk, Gilead and Intercept; Patents planned, issued or pending: Co-Inventor patent on medical use of nor-UDCATS: Grants or contracts from any entity: AbbVie and Roche; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, Roche, Sanofi, Takeda and NovartisCC: Grants or contracts from any entity: AbbVie, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer; Consulting fees: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer; Participation on a Data Safety Monitoring Board or Advisory Board: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma and Pfizer; Leadership or fiduciary role in other board, society, committee or advocacy group: Romanian Society of Rheumatology, Romanian Registry of Rheumatic Diseases and Romanian League against RheumatismMKC: Grants or contracts from any entity: Gilead; Consulting fees: AstraZeneca, BMS, GSK and Shannon Pharmaceuticals; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca and Gilead; Leadership or fiduciary role in other board, society, committee or advocacy group: Arthritis Foundation, New York Chapter; Stock or stock options: Johnson and Johnson, Regeneron and AmgenMD: All support for the present manuscript: Medical academy of Vienna; Grants or contracts from any entity: Roche, Sanofi, Pfizer, AbbVie, Eli Lilly, BMS, Merck, Galapagos and UCB; Consulting fees: Roche, Sanofi, Pfizer, AbbVie, Eli Lilly, BMS, Merck, Galapagos and UCB; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, Sanofi, Pfizer, AbbVie, Eli Lilly, BMS, Merck, Galapagos and UCBGP: none. DvdH: Consulting fees: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer and UCB Pharma; Other financial or non-financial interests: Director of Imaging Rheumatology bv.PE: Grants or contracts from any entity: Abbvie, BMS, Lilly, Novartis, Pfizer, Roche and Samsung; Consulting fees: Abbvie, Astra-Zeneca, Boehringer Ingelheim, Galapagos, Gilead, Eli Lilly and Novartis; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Abbvie, BMS, GSK, Eli Lilly and NovartisEM: All support for the present manuscript: University of Vienna funding; Grants or contracts from any entity: Roche, Jansen, Pfizer, AbbVie and Novartis; Consulting fees: GSK, Roche, Novartis, AbbVie, Pfizer, Janssen, Eli Lilly and AstraZeneca; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: GSK, Pfizer, AbbVie, Lilly, Amgen, Janssen and AstraZeneca; Participation on a Data Safety Monitoring Board or Advisory Board: GSKRF: Consulting fees: AbbVie, Amgen, BMS, GSK, Gilead, Pfizer, Novartis and Eli Lilly; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie and Pfizer; Participation on a Data Safety Monitoring Board or Advisory Board: AbbVie, Pfizer, Eli Lilly and GSKCG: noneKH: Grants or contracts from any entity: Pfizer and BMS; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbViePAM: Grants or contracts from any entity: AbbVie, AstraZeneca, Boeringher-Ingelheim, Bristol-Myers Squibb, ChemoCentryx, Eicos, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Sanofi and Takeda; Royalties or licenses: UpToDate; Consulting fees: AbbVie, AstraZeneca, Boeringher-Ingelheim, Bristol-Myers Squibb, ChemoCentryx, CSL Behring, Dynacure, EMDSerono, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, Immagene, InflaRx, Jannsen, Kiniksa, Kyverna, Magenta, MiroBio, Mitsubishi, Neutrolis, Novartis, Pfizer, Regeneron, Sparrow, Takeda and TalarisTT: Grants or contracts from any entity: Chugai Pharmaceutical; Consulting fees: Chugai, Janssen and Rpharma; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Chugai, BMS, Janssen and SanofiXM: Consulting fees: BMS, Novartis, Galapagos, Sanofi, GSK, Pfizer, Janssen and UCBKW: Grants or contracts from any entity: BMS and Pfizer; Consulting fees: AbbVie, BMS, Eli Lily, Galapagos, Gilead, Pfizer, Roche, UCB, GSK, Novartis, AstraZeneca, Regeneron and SanofiMdW: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Pfizer, Celgene, Eli Lilly and UCBKP: Payments for lectures: Roche, AbbVie, Pfizer, Eli Lilly, Amgen, SOBI, UCB and MSD; Advisory Board: Roche, AbbVie, Pfizer, Eli Lilly, Amgen, SOBI, UCB and MSDPN: Grants or contracts from any entity: Roche, Abbvie, Pfizer, Janssen, Gilead/Galapagos, BMS, Novartis and Eli Lilly; Consulting fees: Abbvie, Pfizer, janssen, BMS, Novartis, Lilly, Roche and Gilead/Galapagos; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Abbvie, Pfizer, janssen, BMS, Novartis, Lilly, Roche and Gilead/GalapagosYT: Grants or contracts from any entity: Asahi-Kasei, Abbvie, Chugai, Mitsubishi-Tanabe, Eisai, Takeda, Corrona, Daiichi-Sankyo, Kowa and Behringer-Ingelheim; Consulting fees: Eli Lilly, Daiichi-Sankyo, Taisho, Ayumi, Sanofi, GSK and Abbvie; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Gilead, AbbVie, Boehringer-Ingelheim, Eli Lilly, Mitsubishi-Tanabe, Chugai, Amgen, YL Biologics, Eisai, Astellas, Bristol-Myers and AstraZenecaCD: Grants or contracts from any entity: FWF Austria and Celgene; Consulting fees: AbbVie, MSD, Pfizer, Roche, Sanofi, Janssen, Novartis, Eli Lilly and Galapagos; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, MSD, Pfizer, Roche, Sanofi, Janssen, Novartis, Eli Lilly and Galapagos; Support for attending meetings and/or travel: AbbVie, MSD, Pfizer, Roche, Sanofi, Janssen, Novartis, Eli Lilly and Galapagos; Receipt of equipment, materials, drugs, medical writing, gifts or other services: MSDMLH: Grants or contracts from any entity: Novartis, Roche and Sandoz; Consulting fees: BMS and Samsung Bioepis; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: MSD, AbbVie, Novartis, Merck, Eli Lilly, Medac and Sandoz; Support for attending meetings and/or travel: The DANBIO registry; Participation on a Data Safety Monitoring Board or Advisory Board: CellTrion and Eli Lilly; Leadership or fiduciary role in other board, society, committee or advocacy group: Chair of the DANBIO steering committee, Member of the Danish Rheumatism Association’s Board, Member of the Danish Rheumatism Association’s research council, Member of EULAR Quality of Care Committee, Co-chair of the EuroSpA collaboration; Receipt of equipment, materials, drugs, medical writing, gifts or other services: Study drug for the NORD-STAR study/ Abatacept and Certolizumab pegolHSK: Consulting fees: Roche, Chugai and Sanofi-Aventis; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, Chugai and Sanofi-Aventis; Participation on a Data Safety Monitoring Board or Advisory Board: Roche, Chugai and Sanofi-AventisMN: Grants or contracts from any entity: Pfizer, Amgen, Galapagos and AbbVie; Consulting fees: AbbVie; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Celgene and AbbVie; Participation on a Data Safety Monitoring Board or Advisory Board: AbbVieAS: Grants or contracts from any entity: oint, unconditional grant from AbbVie, Amgen, BMS, Celltrion, Fresenius Kabi, Hexal, Lilly, MSD, Viatris, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis and UCB; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, Pfizer, Roche, Sanofi and UCBAL: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, MSD, Alfasigma, Celltrion, BMS, Celgene, Eli-Lilly, Sanofi Genzyme, Pfizer, Galapagos, Gilead, Novartis and SOBIAR: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, Angelini, Pfizer, Novartis, Reckitt Benckiser and SOBI; Leadership or fiduciary role in other board, society, committee or advocacy group: President, Pediatric Rheumatology European Society (PReS)ARR: Consulting fees: Sanofi, Roche, AbbVie, Eli Lilly, Gilead, BMS and Novartis; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, Pfizer, Sanofi, UCB, BMS, Gilead, Roche, Novartis and Janssen; Payment for expert testimony: AbbVie, Novartis and Gilead; Support for attending meetings and/or travel: AbbVie and Sanofi; Participation on a Data Safety Monitoring Board or Advisory Board: RPharmIM: Grants or contracts from any entity: AbbVie, BMS, Eli Lilly, Janssen, Pfizer, UCB, Amgen and Novartis; Consulting fees: AbbVie, BMS, Eli Lilly, Janssen, Pfizer, Sanofi, Novartis, Gilead, Amgen, UCB, GSK and Moonlake; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie; Leadership or fiduciary role in other board, society, committee or advocacy group: Vice Principal & Head of MVLS College/University of Glasgow, Board Member/ NHS Greater Glasgow & Clyde and Evelo; Stock or stock options: Causeway Therapeutics, Compugen, Cabaletta and EveloBio; JS: grants to his institution from Abbvie, Astro, AstraZeneca, Janssen, Lilly, Merck Sharpe & Dohme, Pfizer, and Roche; Expert advice for, or had symposia speaking engagements with, AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO Pharma, Janssen, Lilly, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, R-Pharm, Roche, Samsung, Sanofi and UCB., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study was to investigate the effect of treat-to-target combination therapy with intensification at 13 weeks in early RA., Methods: Early RA patients were classified as being at high or low risk of worsening RA based on disease activity and prognostic factors. High-risk patients received COBRA-light (prednisolone 30 mg/day tapered to 7.5 mg/day, MTX increasing to 25 mg/week), and low-risk patients received MTX monotherapy increasing to 25 mg/week. The primary outcome (target) was DAS44 < 1.6 or EULAR good response at 26 weeks. At 13 weeks, non-responders were randomized to (open-label) intensification [high-risk patients: prednisolone 60 mg/day tapered to 7.5 mg/day, addition of SSZ (2 g/day) and HCQ (400 mg/day); low-risk patients: prednisolone 30 mg/day tapered to 7.5 mg/day] or continuation., Results: In the high-risk group (n = 150), 110 patients (73%) reached the target at 13 weeks, and 9 dropped out. Non-responders were randomized to intensification (n = 15) or continuation (n = 16), and after 26 weeks, 12 (80%) vs 7 (44%) of these, respectively, reached the target [difference: 36%, (95% CI 2%, 71%); P = 0.04]. In the low-risk group (n = 40), 17 (43%) reached the target. Non-responders were randomized to intensification (n = 8) or continuation (n = 7); 4 vs 3, respectively, reached the target.Adverse event rates were higher in the high-risk group, and higher in the intensification subgroup of that group. Serious adverse events were rare. Protocol violations were frequent and mostly led to mitigation of actual treatment intensification., Conclusion: Initial combination therapy was very successful in high-risk RA, and early intensification was beneficial in patients not reaching the strict target. The low-risk group was too small for drawing conclusions. In routine practice, adherence to early intensification based on strict targets is difficult., Trial Registration: Netherlands Trial Register (NTR), NL4393, https://www.trialregister.nl/., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Routine collection of electronic patient-reported outcomes (ePROs) can improve clinical care. However, a low response rate may counteract the benefits. To optimize adoption, the aim of this study was to investigate which patient factors and/or timing of the invitation predicted response to ePROs sent prior to consultations in patients with rheumatoid arthritis. We performed a retrospective database study with clinical data collected as part of usual care from the electronic medical records at Reade Amsterdam. The dataset comprised the email invitations to complete the ePRO sent prior to consultation. Multiple patient factors and factors defining the timing of the invitation were investigated if they predicted response to the ePRO through a multivariable logistic generalized estimating equation analysis. In total, 17.070 ePRO invitations were sent to 3194 patients (mean age 60 (SD 14), 74% female), of which 40% was completed. Patients between 55 and 73 years (OR 1.39, 95%CI 1.09-1.77) and with higher social economic status (SES) (OR 1.51, 95%CI 1.22-1.88) had significantly higher odds for completing the ePRO, while patients living in an urban area had lower odds (OR 0.69, 95% CI 0.62-0.76). In year 4 after implementation, the OR was increased to 3.69 (95% CI 2.91-4.90). The implementation of ePROs in daily clinical practice needs improvement since 40% of the ePROs sent prior to consultations were completed. Patients that had higher odds to report the next ePRO were between the age of 55-73, had a higher socio-economic status, and were residents in a rural area. The adoption of reporting the PRO increased over time, but the timing of the prompt did not predict response. Additional research is needed to understand ePRO completion, especially for patients with lower socio-economic status., (© 2023. The Author(s).)

Telemonitoring disease activity with electronic patient-reported outcomes (ePROs) may reduce the workload of rheumatic care by decreasing outpatient clinic visits. However, low adherence to reporting ePROs is frequently observed. Our objective was to identify facilitators and barriers to weekly monitoring of disease activity with ePROs. Patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) who recently participated in one of the two telemonitoring studies with ePROs completed in a smartphone app, were invited to participate in focus group discussions (FGD). Thematic analysis was used to identify themes that play a role in the decision to continue or stop reporting weekly ePROs. A total of 22 patients participated in three FGDs. Five themes were identified that were of importance to adhere to telemonitoring: (1) questionnaire frequency, (2) discussing results of completed ePROs, (3) physical consultations, (4) patient insight into disease activity and (5) user experience of the app. All themes contained both barrier and facilitator elements. The results suggest that to improve adherence to telemonitoring of disease activity with ePROs, the perceived benefits of completing ePROs should be maximized. This can be done by providing patients the ability to skip (unneeded) physical consultations in case of low disease activity, and training clinicians to always discuss the completed ePROs. In addition, it is essential to reduce the effort to report ePROs, by tailoring the frequency of ePROs based on the patients' disease activity or preference, aiming for optimal app functionality as well as by sending notifications when new ePROs are available., (© 2023. The Author(s).)

Objective: To investigate the pharmacokinetics of methotrexate polyglutamate (MTX-PG) accumulation in red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) in patients with early rheumatoid arthritis (RA) after oral and subcutaneous MTX treatment., Methods: In a clinical prospective cohort study (Methotrexate Monitoring study), newly diagnosed patients with RA were randomised for oral or subcutaneous MTX. At 1, 2, 3 and 6 months after therapy initiation, blood was collected and RBCs and PBMCs were isolated. MTX-PG 1-6 concentrations were determined by mass spectrometry methods using stable isotopes of MTX-PG 1-6 as internal standards., Results: 43 patients (mean age: 58.5 years, 77% female) were included. PBMCs and RBCs revealed disparate pharmacokinetic profiles in both absolute MTX-PG accumulation levels and distribution profiles. Intracellular MTX-PG accumulation in PBMCs was significantly (p<0.001) 10-fold to 20-fold higher than RBCs at all time points, regardless of the administration route. MTX-PG distribution in PBMCs was composed of mostly MTX-PG 1 (PG 1 >PG 2 >PG 3 ). Remarkably, the distribution profile in PBMCs remained constant over 6 months. RBCs accumulated mainly MTX-PG 1 and lower levels of MTX-PG 2-5 at t=1 month. After 3 months, MTX-PG 3 was the main PG-moiety in RBCs, a profile retained after 6 months of MTX therapy. Subcutaneous MTX administration results in higher RBC drug levels than after oral administration, especially shortly after treatment initiation., Conclusions: This is the first study reporting disparate MTX-PG accumulation profiles in RBCs versus PBMCs in newly diagnosed patients with RA during 6 months oral or subcutaneous MTX administration. This analysis can contribute to improved MTX therapeutic drug monitoring for patients with RA., Trial Registration Number: NTR 7149., Competing Interests: Competing interests: RCFH: grant/research support from: Pfizer, Amsterdam UMC (research school Amsterdam Infection & Immunology Institute) and NVKC (Dutch Society for Clinical Chemistry). ML, MBC, IBM, SM, SH, EAS, WL, BJFvdB, GJ: none declared. MTN: research support from Pfizer. RdJ: grant from Dutch Society of Clinical Chemistry (NVKC)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate real-world persistence and effectiveness of the IL-12/23 inhibitor, ustekinumab or a tumour necrosis factor inhibitor (TNFi) for psoriatic arthritis over 3 years., Methods: PsABio (NCT02627768), a prospective, observational study, followed patients with PsA prescribed first-line to third-line ustekinumab or a TNFi. Persistence and effectiveness (achievement of clinical Disease Activity for PSA (cDAPSA) low disease activity (LDA)/remission and minimal disease activity/very LDA (MDA/VLDA)) were assessed every 6 months. Safety data were collected over 3 years. Analyses to compare the modes of action were adjusted on baseline differences by propensity scores (PS)., Results: In 895 patients (mean age 49.8 years, 44.7% males), at 3 years, the proportion of patients still on their initial treatments was similar with ustekinumab (49.9%) and TNFi (47.8%). No difference was seen in the risk of stopping/switching; PS-adjusted hazard ratio (95% CI) for stopping/switching ustekinumab versus TNFi was 0.87 (0.68 to 1.11). In the overall population, cDAPSA LDA/remission was achieved in 58.6%/31.4% ustekinumab-treated and 69.8%/45.0% TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.89 (0.63 to 1.26) for cDAPSA LDA; 0.72 (0.50 to 1.05) for remission. MDA/VLDA was achieved in 41.4%/19.2% of ustekinumab-treated and 54.2%/26.9% of TNFi-treated patients with overlapping PS-adjusted ORs. A greater percentage of TNFi-treated patients achieved effectiveness outcomes. Both treatments exhibited good long-term safety profiles, although ustekinumab-treated patients had a lower rate of adverse events (AEs) versus TNFi., Conclusion: At 3 years, there was generally comparable persistence after ustekinumab or TNFi treatment, but AE rates were lower with ustekinumab., Competing Interests: Competing interests: LG reports personal fees from Janssen during the conduct of the study, grants from Amgen, Galapagos, Lilly, Pfizer, Sandoz, UCB, personal fees from AbbVie, Amgen, BMS, Celltrion, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, UCB outside the submitted work. SS reports non-financial support from Janssen during the conduct of the study, personal fees from AbbVie, grants and personal fees from Amgen (previously Celgene), personal fees from Biogen, grants from Boehringer-Ingelheim, grants from Bristol-Myers-Squibb, personal fees from GlaxoSmithKline, grants and personal fees from Janssen, personal fees from Novartis, grants and personal fees from UCB outside the submitted work. PB reports personal fees from Janssen and personal fees from Johnson & Johnson during the conduct of the study. KdV reports personal and consulting fees from Janssen. EG reports payment or honoraria from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer and Sanofi. BJ-I reports consulting fees from Amgen, Janssen and UCB and payment or honoraria from AbbVie, Eli Lilly, Janssen, Novartis and UCB. TVK reports consulting fees from AbbVie, Amgen, BIOCAD, Eli Lilly, Janssen, MCD, Novartis, Pfizer, Sandoz and UCB, and payment or honoraria from AbbVie, Amgen, BIOCAD, Eli Lilly, Janssen, MCD, Novartis, Pfizer, Sandoz and UCB. FL reports non-financial support from Janssen during the conduct of the study. WM is a full-time employee of and owns stock at Johnson & Johnson. MTN reports grants and non-financial support from Janssen during the conduct of the study, grants and personal fees from AbbVie, grants from BMS, grants and personal fees from Eli Lilly, grants from Amgen, grants from Pfizer, and grants from Galapagos outside the submitted work. PPS reports non-financial support from Janssen during the conduct of the study, grants and personal fees from AbbVie, grants from UCB, grants and personal fees from Eli Lilly, grants and personal fees from Pfizer, grants and personal fees from Novartis, and personal fees from MSD outside the submitted work. MS reports non-financial support from Janssen during the conduct of the study. ET was an employee of Janssen during the conduct of the study and preparation of this paper. JSS has nothing to disclose. LG and MTN are editorial board members at the Annals of the Rheumatic Diseases., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Controlling inflammation with tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) patients is hypothesized to reduce their cardiovascular risk. We performed a systematic review and meta-analysis on the effects of TNF inhibitors on arterial stiffness and carotid intima media thickness (IMT) in RA. MEDLINE, EMBASE, clinicaltrials.gov , and WHO Clinical Trials Registry were searched up to September 2021 for randomized controlled trials, prospective cohort studies, and nonrandomized clinical trials evaluating the effects of TNF inhibitors on pulse wave velocity (PWV), augmentation index (AIx), and IMT in RA. A meta-analysis was performed to assess changes of these measures after therapy during different follow-up periods. Risk of bias assessment was performed using an adjusted Downs and Black checklist (INPLASY: 2022-1-0131). Thirty studies were identified from 1436 records, of which 23 were included in the meta-analysis. PWV and AIx showed a decrease after treatment (PWV: mean difference (MD) -0.51 m/s (95% CI: -0.96, -0.06), p=0.027; AIx: MD -0.57% (95% CI: -2.11, 0.96), p=0.463, sensitivity analysis AIx: MD -1.21% (95% CI: -2.60, 0.19), p=0.089). For IMT, there was a slight increase in the first months of follow-up, but this disappeared on the long-term (overall timepoints MD -0.01 mm (95% CI: -0.04, 0.02), p=0.615). Heterogeneity was high in the overall analyses and subgroups with long follow-up periods (≥12 months). The included studies showed mixed results of the effects of TNF inhibitors on the surrogate markers. The pooled results suggest that PWV and AIx decrease over time, while IMT remains stable. This indicates a favorable effect of TNF inhibitors on the cardiovascular disease risk, all the more since these markers also increase with age., (© 2023. The Author(s).)

Background: We aimed to investigate course and burden over time of ADRs attributed to TNFα-inhibitors in IRD-patients, and whether Sankey diagrams and polar plots can visualize this., Research Design and Methods: Data on ADRs experienced during the Dutch Biologic Monitor (January 2017 till December 2022) were used in this study. We selected IRD-patients using a TNFα-inhibitor, reporting skin reactions/infections/injection site reactions and completing ≥3 questionnaires (i.e. the initial report and ≥2 follow-ups). Course was scored as worsening/improving/remaining stable/resolving and as (non-)recurrent. Patients scored burden from 1 (no burden) to 5 (very high burden). Sankey diagrams and polar plots visualized this., Results: 202 patients were included, reporting 353 ADRs. Most skin reactions were stable (25.0%). Most infections resolved (50.8%). Injection site reactions were mostly recurrent (72.3%). Skin reactions and infections tended to decrease in burden . Infections had highest burden at start, which mostly decreased over time. Injection site reactions had a low and stable burden., Conclusions: Skin reactions attributed to TNFα-inhibitors by IRD-patients are stable with a slightly decreasing burden over time. Infections have highest burden at start but resolved mostly. Injection site reactions have a low and stable burden. Sankey diagrams and polar plots are suitable to visualize this.

Objective: To examine the prevalence of hip involvement between sexes in patients with ankylosing spondylitis (AS) treated with tumor necrosis factor inhibitors (TNFi) and to estimate the effect of TNFi on radiographic progression of hip involvement compared to the spine., Methods: Two hundred ninety-nine patients with AS treated with TNFi (215 men; median age: 43 yrs [IQR 36-52], median disease duration: 7.6 yrs [IQR 2-15]) were evaluated for hip involvement, defined radiographically as Bath AS Radiological Hip Index (BASRI-hip) score ≥ 2. Those who received TNFi for ≥ 2 years (263/299) were assessed for radiographic progression. Radiographs of the pelvis and spine, obtained at baseline (ie, before TNFi initiation), were compared retrospectively to those obtained after 2.5 (SD 0.7) years and 7.0 (SD 2.3) years of TNFi treatment. Both hips were scored by BASRI-hip score and mean joint space width (MJSW). Spinal radiographs were scored by modified Stoke AS Spinal Score (mSASSS)., Results: The prevalence of hip involvement at baseline was 113/299 (38%) patients, of whom 87/215 (41%) were male and 26/84 (31%) were female ( P = 0.10). In both sexes with hip involvement at baseline, BASRI-hip score and MJSW did not change significantly during follow-up. In males and females without baseline hip involvement, the BASRI-hip score remained unchanged after 2.5 (SD 0.7) years but increased significantly after 7.0 (SD 2.3) years, without reaching the cut-off of 2. In contrast, the MJSW slightly decreased at the 2 follow-up timepoints (ie, after 2.5 and 7.0 yrs). The mSASSS increased significantly during the follow-up in both sexes, regardless of hip involvement., Conclusion: In our study, approximately one-third of patients with AS had hip involvement, which seemed to stabilize with TNFi treatment. No sex differences in the prevalence or progression of this manifestation were found., (Copyright © 2023 by the Journal of Rheumatology.)

Background: The extent to which adverse drug reactions (ADRs) of biologics differ per immune-mediated inflammatory disease (IMID), and the relevance of tailoring ADR information per IMID is not fully investigated. We aimed to compare patient-reported ADRs attributed to adalimumab and etanercept between different inflammatory rheumatic diseases (IRDs)., Research Design and Methods: ADR reports from IRD patients were extracted from the Dutch Biologic Monitor. ADR frequencies were compared using Fischer-Freeman-Halton exact test and the influence of covariates was assessed using binomial logistic regression., A total, of 729 participants were included, of which 354 participants reported 887 unique ADRs. ADR frequencies were not significantly different between the IRDs. Rheumatoid arthritis and ankylosing spondylitis including axial spondyloarthritis patients had an increased risk of ADRs related to 'Respiratory, thoracic and mediastinal disorders' and as compared to psoriatic arthritis patients. Etanercept use, combination therapy with methotrexate and/or corticosteroids, and age also influenced the risk of reporting specific ADRs., Conclusions: There were no differences in frequencies and nature of patient-reported ADRs attributed to adalimumab and etanercept between different IRDs. However, more research is needed to align patients' and health-care professionals' perspectives to improve knowledge on disease-specific ADRs.

Objective: To assess the effect of 4 years of anti-inflammatory therapy on markers of subclinical vascular disease in rheumatoid arthritis patients., Methods: Carotid intima media thickness (IMT), augmentation index (AIx@75) and pulse wave velocity (PWV) measurements were performed repeatedly in 61 RA patients (30 early RA starting with csDMARDs and 31 established RA starting with adalimumab) for 4 years. These markers were also measured in 29 controls with osteoarthritis at baseline (BL)., Results: IMT and AIx@75 at BL were higher in RA compared to OA, while PWV was higher in OA. In RA patients, AIx@75 and PWV decreased in the first 6 months after starting anti-inflammatory therapy. At 48 M, the level of AIx@75 remained lower than before therapy, while PWV at 48 M was comparable to BL (AIx@75: BL 28% (95% confidence interval 25-30%), 6 M 23% (20-26%), 48 M 25% (22-28%); PWV: BL 8.5 (7.8-9.2), 6 M 8.0 (7.1-8.9), 48 M 8.6 (7.6-9.6) m/s). IMT remained stable. There was an effect of disease activity (longitudinally, adjusted for changes over time) on IMT, AIx@75 and PWV., Conclusion: This study suggests modest beneficial changes in some surrogate markers of subclinical vascular disease after anti-inflammatory therapy. These changes were associated with improvement in disease activity markers. Whether or not these beneficial changes ultimately predict a reduction in clinicalcardiovascular endpoints remains to be established in prospective studies., (© 2022. The Author(s).)

Background: We examine sex differences in relation to the nature, frequency, and burden of patient-reported adverse drug reactions (ADRs) in patients with inflammatory rheumatic diseases., Research Design and Methods: Rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis patients using etanercept or adalimumab from the Dutch Biologic Monitor were sent bimonthly questionnaires concerning experienced ADRs. Sex differences in the proportion and nature of reported ADRs were assessed. Additionally, 5-point Likert-type scales reported for the burden of ADRs, were compared between sexes., Results: In total 748 consecutive patients were included (59% female). From the women 55% reported ≥1 ADR, which was significantly higher than 38% of the men that reported ≥1 ADR (p < 0.001). A total of 882 ADRs were reported comprising 264 distinct ADRs. The nature of the reported ADRs differed significantly between both sexes (p = 0.02). Women in particular reported more injection site reactions than men. The burden of ADRs was similar between sexes., Conclusions: Sex differences in the frequency and nature of ADRs, but not in ADR burden, exist during treatment with adalimumab and etanercept in patients with inflammatory rheumatic diseases. This should be taken into consideration when investigating and reporting results on ADRs and when counseling patients in daily clinical practice.

Aims: In immune-mediated inflammatory diseases (IMIDs), early symptom control is a key therapeutic goal. Methotrexate (MTX) is the first-line treatment across IMIDs. However, MTX is underutilized and suboptimally dosed, partly due to the inability of making individualized treatment decisions through therapeutic drug monitoring (TDM). To implement TDM in clinical practice, establishing a relationship between drug concentration and disease activity is paramount. In this meta-analysis, we investigated the relationship between concentrations of MTX polyglutamates (MTX-PG) in erythrocytes and efficacy as well as toxicity across IMIDs., Methods: Studies analysing MTX-PG in relation to disease activity and/or toxicity were included for inflammatory arthritis (rheumatoid [RA] and juvenile idiopathic arthritis [JIA]), inflammatory bowel disease (Crohn's and ulcerative colitis) and dermatitis (psoriasis and atopic dermatitis). Meta-analyses were performed resulting in several summary effect measures: regression coefficient (β), correlation coefficient and mean difference (of MTX-PG in responders vs. nonresponders) for IMIDs separately and collectively., Results: Twenty-five studies were included. In RA and JIA, higher MTX-PG was significantly associated with lower disease activity at 3 months (β: -0.002; 95% confidence interval [CI]: -0.004 to -0.001) and after 4 months of MTX use (β: -0.003; 95% CI: -0.005 to -0.002). Similarly, higher MTX-PG correlated with lower disease activity in psoriasis (R: -0.82; 95% CI: -0.976 to -0.102). Higher MTX-PG was observed in RA, JIA and psoriasis responders (mean difference: 5.2 nmol/L MTX-PG total ; P < .01)., Conclusion: We showed that higher concentrations of erythrocyte MTX-PG were associated with lower disease activity in RA, JIA and psoriasis. These findings are an important step towards implementation of TDM for MTX treatment across IMIDs., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objectives: Rituximab (RTX) is a safe and effective treatment for RA. A dose-dependent infection risk was found in the REDO trial. Some studies associate RTX use with higher infection risks, possibly explained by low immunoglobulin levels and/or neutropenia. Additionally, a higher infection risk shortly after RTX infusion is reported. The objectives of this study were (i) to compare incidence rates of infections between doses and over time, and (ii) to assess B-cell counts, immunoglobulin levels, neutrophil counts and corticosteroid/disease modifying rheumatic drug use as mediating factors between RTX study dose and infection risk., Methods: Post hoc analyses of the REDO trial were performed. Infection incidence rates between RTX dosing groups and between time periods were compared using Poisson regression. A step-wise mediation analysis was performed to investigate if any of the factors mentioned above act as a mediator in the observed dose-dependent difference in infection risk., Results: The potential mediators that were investigated (circulating B-cell counts, immunoglobulin levels, neutrophil counts and drug use) did not explain the dose-dependent infection risk observed in the REDO trial. Additionally, a trend towards a time-dependent infection risk was found, with higher infection rates shortly after RTX infusion., Conclusions: These secondary analyses of the REDO trial confirmed the observed dose-dependent infection risk. Additionally, we found that infection risks were higher shortly after RTX infusion. However, a mediating pathway was not found., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Patients with rheumatoid arthritis require frequent consultations to monitor disease activity and intensify medication when treatment targets are not met. However, because most patients are in remission during follow-up, it should be possible to reduce the number of consultations for them. Electronic patient-reported outcomes (ePROs) could be used to identify patients who meet their treatment goal and who could therefore be eligible to skip their visit., Objective: The aim of this study was to assess the probability that patients with low disease activity scores on their ePROs do not need a disease-modifying antirheumatic drug (DMARD) or steroid intensification in the first 2 weeks after completion of the ePROs., Methods: This medical-records review study compared results of ePROs answered during routine care with DMARD or steroid intensifications collected from anonymized electronic medical record at Reade. The primary outcome was the positive predictive value (PPV) of having a low disease activity score on an ePRO for not receiving a DMARD or steroid intensifications within 2 weeks. The 3 studied ePROs (and respective low disease activity outcome) were the Routine Assessment of Patient Index Data 3 (RAPID3) (score <2), Patient Acceptable Symptom State (PASS) (yes), and the flare question (no). The secondary aim of the study was to assess which combination of ePROs resulted in the best PPV for DMARD or steroid intensifications., Results: Of the 400 randomly selected records, ultimately 321 were included (302 unique patients). The PPV of a RAPID3 <2, being in PASS, and a negative answer on the flare question were, respectively, 99%, 95%, and 83% to not receive a DMARD or steroid intensification within 2 weeks. The combination of a RAPID3 <2 and a negative flare question resulted in a PPV of 100%; this combination was present in 29% (93/321) of the total study population., Conclusion: The RAPID3, PASS, and flare question have a high diagnostic accuracy to identify individuals who will not receive a DMARD or steroid intensification in the following 2 weeks. The combination of the RAPID3 and flare question yielded the best combination of diagnostic accuracy and highest percentage of patients who could be eligible to skip a visit. These results suggest that accurate identification of patients who meet their treatment goal with ePROs is possible., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We developed a smartphone application for patients with rheumatoid arthritis (RA) that allows them to self-monitor their disease activity in between clinic visits by answering a weekly Routine Assessment of Patient Index Data 3. This study was undertaken to assess the safety (noninferiority in the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28-ESR]) and efficacy (reduction in number of visits) of patient-initiated care assisted using a smartphone app, compared to usual care., Methods: A 12-month, randomized, noninferiority clinical trial was conducted in RA patients with low disease activity and without treatment changes in the past 6 months. Patients were randomized 1:1 to either app-supported patient-initiated care with a scheduled follow-up consultation after a year (app intervention group) or usual care. The coprimary outcome measures were noninferiority in terms of change in DAS28-ESR score after 12 months and the ratio of the mean number of consultations with rheumatologists between the groups. The noninferiority limit was 0.5 difference in DAS28-ESR between the groups., Results: Of the 103 randomized patients, 102 completed the study. After a year, noninferiority in terms of the DAS28-ESR score was established, as the 95% confidence interval (95% CI) of the mean ΔDAS28-ESR between the groups was within the noninferiority limit: -0.04 in favor of the app intervention group (95% CI -0.39, 0.30). The number of rheumatologist consultations was significantly lower in the app intervention group compared to the usual care group (mean ± SD 1.7 ± 1.8 versus 2.8 ± 1.4; visit ratio 0.62 [95% CI 0.47, 0.81])., Conclusion: Patient-initiated care supported by smartphone self-monitoring was noninferior to usual care in terms of the ΔDAS28-ESR and led to a 38% reduction in rheumatologist consultations in RA patients with stable low disease activity., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: To evaluate retention, efficacy, and safety of subcutaneous (SC) abatacept over 2 years in patients with moderate-to-severe RA in the Abatacept SubCutaneOus in Routine clinical practicE (ASCORE) study., Methods: Patients with RA who initiated SC abatacept 125 mg once weekly were enrolled in the international, observational, prospective multicentre ASCORE study into biologic-naïve or ≥ 1 prior biologic failure cohorts., Primary Endpoint: abatacept retention rate at 2 years. Secondary endpoints: proportion of patients with good/moderate EULAR response rates based on DAS28 (ESR), low disease activity and/or remission according to DAS28 (ESR; ≤ 3.2/ < 2.6), SDAI (≤ 11/ ≤ 3.3), CDAI (≤ 10/ ≤ 2.8), and Boolean criteria. Retention rate by baseline serostatus was evaluated post hoc., Results: Overall, 47% of patients remained on abatacept for 2 years, irrespective of treatment line. Higher abatacept retention rates were associated with lower prior biologic exposure. Generally, clinical outcomes showed that the proportion of patients with low disease activity/remission was higher in biologic-naïve patients (vs biologic-failure) and similar in those with 1 and ≥ 2 prior biologic failures. In patients on treatment at 2 years, good/moderate EULAR response rates of ~ 80% were consistently noted irrespective of prior biologic exposure. Across treatment lines, retention was greater in patients with seropositive (vs seronegative) RA. Patients with rheumatoid factor/anti-citrullinated protein antibody single-positive RA who were bio-naïve had higher retention than patients who were bio-experienced., Conclusions: In the ASCORE study, SC abatacept retention was 47% at 2 years with good clinical outcomes and was well-tolerated in the real-world setting. Abatacept retention and clinical response rates were higher in patients who received abatacept as an earlier- versus later-line biologic drug treatment and in those with seropositive RA., Trial Registration: ClinicalTrials.gov, NCT02090556., (© 2022. The Author(s).)

Competing Interests: Competing interests: None declared.

Objective: To develop recommendations for cardiovascular risk (CVR) management in gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS)., Methods: Following European League against Rheumatism (EULAR) standardised procedures, a multidisciplinary task force formulated recommendations for CVR prediction and management based on systematic literature reviews and expert opinion., Results: Four overarching principles emphasising the need of regular screening and management of modifiable CVR factors and patient education were endorsed. Nineteen recommendations (eleven for gout, vasculitis, SSc, MCTD, myositis, SS; eight for SLE, APS) were developed covering three topics: (1) CVR prediction tools; (2) interventions on traditional CVR factors and (3) interventions on disease-related CVR factors. Several statements relied on expert opinion because high-quality evidence was lacking. Use of generic CVR prediction tools is recommended due to lack of validated rheumatic diseases-specific tools. Diuretics should be avoided in gout and beta-blockers in SSc, and a blood pressure target <130/80 mm Hg should be considered in SLE. Lipid management should follow general population guidelines, and antiplatelet use in SLE, APS and large-vessel vasculitis should follow prior EULAR recommendations. A serum uric acid level <0.36 mmol/L (<6 mg/dL) in gout, and disease activity control and glucocorticoid dose minimisation in SLE and vasculitis, are recommended. Hydroxychloroquine is recommended in SLE because it may also reduce CVR, while no particular immunosuppressive treatment in SLE or urate-lowering therapy in gout has been associated with CVR lowering., Conclusion: These recommendations can guide clinical practice and future research for improving CVR management in rheumatic and musculoskeletal diseases., Competing Interests: Competing interests: GCD, DV, EH, LB, SB, DTB, NB, GK, FM, CM, MR-C, KS, SS, VPvH, GJM, MMW and MN have nothing to declare. FA: research grants from BMS, Celgene, Novartis and Sandoz and consulting fees from AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and Sanofi-Aventis, all unrelated to this manuscript; INB: grant from GSK paid to institution, consulting fees from Astra Zeneca, GSK, Eli lilly, UC, MSD paid to institution, support for attending meetings and/or travel from GSK, participation on a data safety monitoring board/or advisory board from Aurinia, Astra Zeneca and ILTOO paid to institution, all unrelated to this manuscript; MÁG-G: grants/research support from AbbVie, MSD, Jansen and Roche paid to institution and personal consulting fees/participation in company sponsored speakers bureau from AbbVie, Pfizer, Roche, Celgene, MSD, Novartis, SOBI and Sanofi, all unrelated to this manuscript; SJ: grants from BMS paid to institution, personal consulting fees from Astra Zeneca, and personal fees from Danish Medicolegal Council, all unrelated to this manuscript; NS: grants paid to institution from Astrazeneca, Boehringer Ingelheim and Roche Diagnostics, personal consulting fees from Afimmune, Amgen, Astrazeneca, Boehringer Ingelheim, Eli-Lilly, Hanmi Pharamceuticals, MSD, Novartis, Novo Nordisk, Pfizer and Sanofi, all unrelated to this manuscript; ES: grant from Merck and honoraria from Janssen, all unrelated to this manuscript; ZS: research grants from Pfizer paid to institution and personal consulting fees from Pfizer, MSD, Lilly, Novartis, Roche, Gedeon Richter, Boehringer Ingelheim, Abbvie, all unrelated to this manuscript; A-KT: speakers fee from Berlin Chemie Menarini, Novarti and personal fees and non-financial support from AstraZeneca and Grünenthal, all unrelated to this manuscript; AT: consulting fees from Magenta Therapeutics and personal fees from Novartis and Idorsia for participation on a Data Safety Monitoring Board or Advisory Board, all unrelated to this manuscript; AV: personal consulting fees from Astra Zeneca and GS, all unrelated to this manuscript; MGT: research grants from Genesis, GSK, MSD, Pfizer and UCB paid to institution, and personal consulting fees from Genesis, GSK and Novartis, all unrelated to this manuscript., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the coagulation system in gout patients and associations between disease activity and levels of coagulation markers., Methods: A prospective cohort study was performed with data from 30 Dutch gout patients. Levels of coagulation markers including APTT, PT, D-dimer, prothrombin F1 + 2, von Willebrand factor, and thrombin generation parameters were analyzed at baseline and 1-year visit. These markers were related to clinical markers of gout disease activity including the Gout Activity Score (GAS). Our hypothesis was that patients with gout and active disease have increased levels of coagulation markers and that a decrease in disease activity would lead to normalization of coagulation activity., Results: A higher GAS was associated with increased levels of thrombin generation parameters including ETP (ß = 0.48, p = 0.01), peak thrombin (ß = 0.60, p = 0.001), and velocity index (ß = 0.57, p = 0.002). Tophaceous gout and higher SUA levels were associated with thrombin generation parameters. After 1 year, thrombin generation parameters showed a small procoagulant trend despite a moderate decrease in disease activity. Prospectively measured changes in disease activity according to the GAS were not associated with any of the coagulation markers., Conclusion: Patients with active gout have higher levels of thrombin generation markers, indicating a link between disease activity and coagulation. A change in disease activity after 1 year was not associated with significant changes in coagulation markers, probably due to prolonged low-grade inflammation. Future studies should focus on levels of coagulation markers in comparison with the general population and the effect of adequate gout treatment. Key Points • Patients with gout have an increased risk of cardiovascular events. • High disease activity was associated with higher levels of thrombin generation markers. • Over time, small decreases in inflammation were associated with a decrease in D-dimer and thrombin generation., (© 2022. The Author(s).)

Objective: We evaluated real-world treatment persistence and effectiveness at 1 year following initiation of IL-12/23 inhibitor ustekinumab or a tumour necrosis factor inhibitor (TNFi) for psoriatic arthritis (PsA)., Methods: PsABio (NCT02627768), a prospective, observational study, followed patients with PsA prescribed first-line to third-line ustekinumab or TNFi. Drug persistence, effectiveness (achievement of clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) low disease activity (LDA)/remission and minimal disease activity/very low disease activity (MDA/VLDA)), and safety were assessed every 6 months. In addition to descriptive statistics, propensity score (PS)-adjusted comparisons across cohorts were performed., Results: At 1 year, overall persistence was similar in the ustekinumab (n=317/438, 72.4%) and TNFi (n=321/455, 70.5%) groups. PS-adjusted HR (95% CI) for stopping/switching ustekinumab versus TNFi was 0.82 (0.60; 1.13). cDAPSA LDA (including remission)/remission was achieved in 55.9%/22.1% of ustekinumab-treated and 67.1%/31.7% of TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.80 (0.57; 1.10) for cDAPSA LDA and 0.73 (0.49; 1.07) for remission. MDA/VLDA was achieved in 34.2%/11.9% of ustekinumab-treated and 43.1%/12.6% of TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.89 (0.63; 1.26) for MDA and 0.90 (0.54; 1.49) for VLDA. The safety profiles were similar in both groups., Conclusion: In the real-world PsABio Study, after 1 year of treatment, although unadjusted persistence was numerically slightly higher for ustekinumab versus TNFi and unadjusted effectiveness was numerically slightly higher for TNFi versus ustekinumab, the PS-adjusted comparisons demonstrated comparable overall persistence, effectiveness and safety for both modes of action in PsA., Competing Interests: Competing interests: LG reports research grants from: Amgen, Galapagos, Lilly, Pfizer, Sandoz, Sanofi; consulting fees from: AbbVie, Amgen, Bristol-Myers Squibb, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB. SS reports non-financial support from Janssen during the conduct of the study; grants from: Boehringer-Ingelheim, Bristol-Myers Squibb; personal fees from: AbbVie, Biogen, Novartis; grants and personal fees from: Amgen (previously Celgene), GlaxoSmithKline, Janssen, UCB; all outside the submitted work. PB is a full-time employee of Janssen and owns stock at Johnson & Johnson. KdV reports personal fees from Janssen. EG reports payment or honoraria from AbbVie, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi. BJI has nothing to disclose. TVK reports consulting fees from MCD, Pfizer, Janssen, BiOCAD, AbbVie, Novartis, Sandoz, Lilly. FL reports non-financial support, full-time employment and restricted share units from Janssen during the conduct of the study. WN is a full-time employee of and owns stock at Johnson & Johnson. MTN reports grants and non-financial support from Janssen during the conduct of the study; grants from: Bristol-Myers Squibb, Amgen, Pfizer; grants and personal fees from: AbbVie, Eli Lilly; all outside the submitted work. PPS reports non-financial support from Janssen during the conduct of the study; grants from: UCB; personal fees from: Merck Sharpe & Dohme; grants and personal fees from: AbbVie, Lilly, Pfizer, Novartis; all outside the submitted work. ET is a full-time employee of Janssen. JSS reports grants to his institution from: AbbVie, Astro, AstraZeneca, Janssen, Lilly, Merck Sharpe & Dohme, Pfizer, and Roche; providing expert advice for or had symposia speaking engagements with: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO Pharma, Janssen, Lilly, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, R-Pharm, Roche, Samsung, Sanofi, and UCB., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The risk for developing cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients is 1.5 times higher compared to the general population. This risk is partly due to the contribution of systemic inflammation in increased atherogenesis, while an increased prevalence of "traditional" cardiovascular risk factors, such as hypertension and dyslipidemia, is also attributed to nearly 50% of the total CVD risk. Most anti-rheumatic medication partly reduces this CVD risk, primarily by reducing inflammation. The increased risk is recognized by most guidelines, which advise consequent screening and multiplying calculated risk scores by 1.5. However, screening in daily clinical practice is poorly done, and RA patients often have undiagnosed and untreated risk factors. In conclusion, even nowadays, RA patients still have an increased risk of developing CVD. Advances in anti-inflammatory treatment partly mitigate this risk, but RA patients need mandatory screening for CV risk factors to turn their CVD risk towards that of the general population.

Aims: Hyperuricaemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. This study aimed to assess whether febuxostat and allopurinol could differently influence carotid-femoral pulse wave velocity (cfPWV) in patients with gout and elevated serum uric acid (SUA) levels., Methods and Results: A multi-centre, multinational, phase IV, randomized, parallel-group, active-controlled, open-label trial with blind endpoints evaluation. One hundred and ninety-seven adults with gout and SUA levels ≥8 mg/dL were randomized to febuxostat or allopurinol in a 1:1 ratio for 36 weeks. The primary outcome was the comparison of the effects of febuxostat and allopurinol on changes in cfPWV. The mean cfPWV values at randomization and Week 36 were 8.69 and 9.00 m/s, respectively for subjects randomized to febuxostat and 9.02 and 9.05 m/s for subjects randomized to allopurinol. No statistically significant changes in cfPWV by treatment assignment were observed at any time point for any of the assessed parameters. More subjects who received febuxostat had serum urate concentrations ≤6 mg/dL following treatment (78.3% vs. 61.1% at Week 36, P = 0.0137). Treatment-emergent adverse events were reported by 51 (52.0%) patients randomized to febuxostat and 63 (62.5%) patients randomized to allopurinol. The majority of events were mild in both treatment groups and included gout flares and arthralgia., Conclusion: In patients with gout and elevated SUA levels the arterial stiffness remained stable both with febuxostat and allopurinol. Febuxostat was more effective and faster than allopurinol in achieving the SUA target. Both treatments were safe and well tolerated., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021.)

Competing Interests: Trial ID NL8513 received funding from ZonMw and the Reade Foundation. TR and GW received funding from ZonMw during the conduct of the study. WHB reports grants and personal fees from Abbvie, Eli Lilly, and Sanofi; personal fees from Galapagos; and grants from Gelgene, Pfizer, Roche, and UCB, outside the submitted work. All other authors declare no competing interests.

Competing Interests: Competing interests: BJFvdB has served on advisory board or as speaker for Galapagos, Eli Lilly and UCB. MBAvD reports grants and has served on advisory board or as speaker for Novartis and Janssen Cilag and has served on advisory board or as speaker for AbbVie, LEO Pharma, BMS, Celgene, Lilly, MSD, Pfizer, Sanofi Genzyme, outside the submitted work. HV has served on advisory boards, or as speaker, or consultant for AbbVie, Amgen, AstraZeneca, BMS, Celgene, Celltrion, Galapagos, Gilead, GSK, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, Roche and Sanofi Genzyme, all outside the submitted work.

Background: Research on the disease severity of COVID-19 in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) has been inconclusive, and long-term prospective data on the development of SARS-CoV-2 antibodies in these patients are lacking., Methods: Adult patients with rheumatic IMIDs from the Amsterdam Rheumatology and Immunology Center, Amsterdam were invited to participate. All patients were asked to recruit their own sex-matched and age-matched control subject. Clinical data were collected via online questionnaires (at baseline, and after 1-4 and 5-9 months of follow-up). Serum samples were collected twice and analysed for the presence of SARS-CoV-2-specific antibodies. Subsequently, IgG titres were quantified in samples with a positive test result., Findings: In total, 3080 consecutive patients and 1102 controls with comparable age and sex distribution were included for analyses. Patients were more frequently hospitalised compared with controls when infected with SARS-CoV-2; 7% vs 0.7% (adjusted OR: 7.33, 95% CI: 0.96 to 55.77). Only treatment with B-cell targeting therapy was independently associated with an increased risk of COVID-19-related hospitalisation (adjusted OR: 14.62, 95% CI: 2.31 to 92.39). IgG antibody titres were higher in hospitalised compared with non-hospitalised patients, and slowly declined with time in similar patterns for patients in all treatment subgroups and controls., Interpretation: We observed that patients with rheumatic IMIDs, especially those treated with B-cell targeting therapy, were more likely to be hospitalised when infected with SARS-CoV-2. Treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and biological DMARDs other than B-cell targeting agents is unlikely to have negative effects on the development of long-lasting humoral immunity against SARS-CoV-2., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: To date, four Janus kinase inhibitors (JAKis) are licensed for the treatment of rheumatoid arthritis (RA) and/or psoriatic arthritis (PsA) in North America and/or Europe: tofacitinib, baricitinib, upadacitinib, and filgotinib. Most DMARDs have cardioprotective potential, yet for some of them, including JAKi, the modulatory effect on cardiovascular risk remains undetermined. Since their commercialization, the risk of venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is taking on a relevant role in RA patients., Areas Covered: In this article, we will review the effect of JAKi on CV risk and atherosclerosis process as major contributor to MACE. Furthermore, we will present the effect of JAKi on thromboembolic risk., Expert Opinion: Although the effect of JAKi on CV and thrombosis is one of the most relevant topic regarding RA patients, it is necessary to underline that these patients have an increased risk of these comorbidities due to the inflammation process, and further study are needed in order to understand the real role of JAKi in controlling or inducing these complications.

Objective: Medication non-adherence in rheumatoid arthritis (RA) is associated with disease flares, increased disability and increased costs. This study assessed the effectiveness of electronic monitoring feedback (EMF) on medication adherence in patients with RA starting with or switching to a new biological disease-modifying antirheumatic drug (bDMARD)., Methods: In this randomised controlled trial, bDMARD starters were assigned to the intervention or control group and followed for 1 year. The intervention group received a needle container with a Medication Event Monitoring System (MEMS) cap registering patient's adherence to injections. Scores were calculated every 3 months with MEMS and motivational interviewing feedback was given. The control group received usual care. Effectiveness of EMF on adherence was measured with the medication possession ratio (MPR)., Results: 104 consecutive intervention patients were included and 102 controls. MPR was 0.95 (SD: 0.10) and 0.90 (0.16) after 12 months (B: 0.036, 95% CI: 0.001 to 0.007, p=0.045). bDMARD-naive patients receiving EMF achieved low disease activity (LDA) sooner compared with the control group, adjusted for baseline DAS (HR: 1.68, 95% CI: 1.00 to 2.81, p=0.050). Side effects and DAS28 were similar., Conclusion: EMF increased adherence for patients with RA starting with or switching to a bDMARD. Especially bDMARD-naive patients achieved LDA sooner compared with the control group, which holds promise for the future., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Rheumatoid arthritis (RA) is associated with cardiovascular (CV) morbidity and mortality. Interferon regulatory factor 5 (IRF5) gene polymorphisms rs2004640 and rs4728142 have been associated with autoimmune diseases, but also with atherosclerosis. Differences in IRF5 gene expression can lead to the production of different interferons and might play a role in the atherogenic process in RA., Methods: We investigated the effects of IRF5 gene variants rs2004640 and rs4728142 on clinical parameters related to atherosclerosis, such as cIMT (in subgroup n=101), and new CV events (in whole cohort n=353)., Results: For rs2004640, cIMT values at baseline were highest within the group of patients carrying the GG-genotype, followed by GT- and TT- genotypes, which was statistically significant. Over time patients with the TT-genotype had the highest increase in cIMT. For rs4728142 cIMT values were also the highest for patients with the GG-genotype at baseline, but the difference between the groups was not statistically significant. Over time the highest increase in cIMT was in the patients with the AA-genotype. Both rs2004640 and rs4728142 were not associated with new CV events during follow-up., Conclusions: IRF5 alleles are associated with changes in cIMT, but not with new CV events in RA. Although these findings implicate a role of the IRF5 transcription pathway in atherosclerosis, IRF5 single nucleotide polymorphisms do not appear to increase the risk of future CV events.

Background: Patient-reported outcomes (PROs) on adverse drug reactions (ADRs) are increasingly used in cohort event monitoring (CEM) to obtain a better understanding of patients' real-world experience with drugs. Despite the leading role for patients, little is known about their perspectives on CEM systems., Research Design and Methods: In a cross-sectional open survey following the rationale of the Technology Acceptance Model, we aimed to obtain insight in patients' perspectives on the perceived usefulness, ease of use and attitude toward using a PRO-based drug safety monitoring system for ADRs attributed to biologics., Results: Patients considered structural reporting of ADRs in web-based questionnaires as useful and not burdensome. It was preferred to link the questionnaire frequency to regular hospital consultations or the biologic administration schedule. Various respondents were interested in sharing questionnaires with their medical specialist (49.0%) or pharmacist (34.2%), and suggested to minimize the questionnaire frequency in case of an unaltered situation or absence of ADRs., Conclusions: Patients' perspectives should be considered in the setup of PRO-based CEM studies, as this contributes to data quality and patient centeredness. Since incorporation of patients' perspectives in CEM studies is indispensable, a delicate balance should be found between user-friendliness and study aims.