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To study the long-term effect of 16 weeks of etanercept treatment on disease activity and radiographic changes in patients with suspected non-radiographic axial spondyloarthritis (nr-axSpA). Eighty patients with inflammatory back pain and suspected nr-axSpA, with a Bath Ankylosing Disease Activity Index (BASDAI) ≥ 4, received etanercept (n = 40) 25 mg twice weekly or placebo (n = 40) for 16 weeks. They were followed without treatment restrictions after 24 weeks, for up to 3 years. Comparisons were made between patients who received etanercept or placebo in the first period, and changes in BASDAI, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Metrology Index (BASMI), function, and radiographic changes in the spine [according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS)] and sacroiliac joints (Bath Ankylosing Spondylitis Radiology Index (BASRI). After 3 years of follow-up, 84% of the patients were diagnosed with SpA, predominantly axSpA. Biological treatment was started after 24 weeks in 30% of patients. Disease activity scores after 3 years did not reveal significant differences between the initial randomization groups in mean BASDAI scores (mean difference 0.9, 95% CI −1.1;0.7, p = 0.6) and ASDAS (mean ASDAS 0.3, 95% CI 0.6;3.1, p = 0.5). BASMI and function scores remained stable over 3 years. No differences in radiographic changes of the sacroiliac joints or spine were observed over 3 years between the two groups. A short course of etanercept in patients with suspected nr-axSpA did not affect disease activity, the chance of biological treatment, or radiographic progression after 3 years of follow-up. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that may result in debilitating joint deformities with destruction of bone and cartilage. Inflammation is still considered the pivotal inducer of both components of joint damage. Results of recent animal studies suggested a prominent contribution of osteoclastic bone resorption that could be dissociated from inflammation. RANKL and its natural decoy receptor, osteoprotegerin (OPG), play key roles in osteoclast activation. In a group of patients with early RA not treated with disease-modifying drugs, we tested the hypothesis that osteoclast activation, reflected by the serum OPG:RANKL ratio at baseline, is negatively associated with progression of bone damage, independent of inflammation. METHODS: OPG and RANKL levels, together with a parameter of inflammation (first-year time-averaged erythrocyte sedimentation rate [tESR]), were measured in 92 patients with newly diagnosed early active RA who were participants in a randomized study. The tESR and the OPG:RANKL ratio were evaluated for the ability to predict 5-year radiographic progression of joint damage. RESULTS: The first-year tESR and the OPG:RANKL ratio, as measured at baseline, independently predicted 5-year radiographic progression of joint damage (both P

OBJECTIVE: To select the most appropriate radiologic scoring method for the evaluation of radiographic progression in ankylosing spondylitis (AS) in clinical trials. METHODS: The validity of the currently available methods, the Bath Ankylosing Spondylitis Radiology Index (BASRI), the Stoke Ankylosing Spondylitis Spine Score (SASSS), and the modified SASSS (M-SASSS), was tested according to the aspects of the Outcome Measures in Rheumatology Clinical Trials filter: truth, discrimination (reliability and sensitivity to change), and feasibility, using radiographs of 133 patients at 4 different time points (baseline, 1 year, 2 years, and 4 years). One observer scored these sets in chronological order. To assess interobserver reliability, a second observer scored radiographs of 20 patients at the 4 different time points. RESULTS: After 4 years, 9% and 8% of patients showed changes >0 in the sacroiliac (SI) joints and hips, respectively. Independent of the method chosen, approximately 40% of patients showed changes in both the lumbar and cervical spine. Therefore, it was concluded that, for the assessment of progression, SI joints and hips are of minor importance. The intraclass correlation coefficient (ICC) varied from 0.87 to 0.98 and ICCs for intraobserver scores varied from 0.96 to 0.99. Concerning progression scores, only the ICC for the M-SASSS measured after 2 years remained acceptable (0.82). The intraobserver scores for progression after 2 years of followup were an ICC of 0.93 for the BASRI, an ICC of 0.79 for the SASSS, and an ICC of 0.95 for the M-SASSS. Concerning sensitivity to change, it was found that the M-SASSS classified the highest percentage of patients with a change >0. CONCLUSION: The M-SASSS is the most appropriate method by which to score the radiographic progression in AS patients in clinical trials. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Radiologic progression in rheumatoid arthritis (RA) is considered the consequence of persistent inflammatory activity. To determine whether a change in disease activity is related to a change in radiologic progression in individual patients, we investigated the longitudinal relationship between inflammatory disease activity and subsequent radiologic progression. METHODS: The databases of the University Medical Center Nijmegen (UMCN) cohort and the Maastricht Combination Therapy in RA (COBRA) followup study cohort were analyzed. The UMCN cohort included 185 patients with early RA who were followed up for up to 9 years. Patients were assessed every 3 months for disease activity and every 3 years for radiologic damage. The COBRA cohort included 152 patients with early RA who were followed up for up to 6 years. Patients were assessed at least every year for disease activity and every 12 months for radiologic damage. Disease activity was assessed with the Disease Activity Score (DAS) (original DAS in the UMCN cohort, DAS28 in the COBRA cohort). Radiologic damage was measured by the Sharp/van der Heijde score in both cohorts. Data were analyzed with longitudinal regression analysis (generalized estimating equations [GEE]), using autoregression for longitudinal associations and radiologic damage as the dependent variable. Time, time(2) baseline predictors for radiologic progression and their interactions with time, as well as DAS/DAS28 (actual values or interval means and interval SDs of the means) were subsequently modeled as explanatory variables. RESULTS: Data analyzed by GEE showed a decrease in radiologic progression over time (regression coefficient for time(2) -1.0 [95% confidence interval -1.4, -0.6] in the UMCN cohort and -0.4 [95% confidence interval -0.8, 0.0] in the COBRA cohort). After adjustment for time effects and baseline predictors of radiologic progression and their interactions with time, a positive longitudinal relationship was indicated by autoregressive GEE between the mean interval DAS and radiologic progression in the UMCN cohort (regression coefficient 5.4 [95% confidence interval 2.1, 8.6]), and between the DAS28 and radiologic progression in the COBRA cohort (regression coefficient 1.4 [95% confidence interval 0.8, 2.0]). In the UMCN cohort, the SD of the mean interval DAS was independently longitudinally related to the radiologic progression over the same periods (regression coefficient 20.2 [95% confidence interval 7.2, 33.3]). In both cohorts, the longitudinal relationships between (fluctuations in) disease activity and radiologic progression were found selectively in rheumatoid factor (RF)-positive patients. CONCLUSION: Radiologic progression is not linear in individual patients. Fluctuations in disease activity are directly related to changes in radiologic progression, which supports the hypothesis that disease activity causes radiologic damage. This relationship might only exist in RF-positive patients. [ABSTRACT FROM AUTHOR]

Objectives: Early treatment of individuals at risk of developing rheumatoid arthritis (RA-risk) in the preclinical phase has the potential to positively impact both patients and society by preventing disease onset and improving patients' quality of life. The PRAIRI study was a randomised, double-blind, placebo-controlled trial with the B-cell depleting agent rituximab (RTX), which resulted in a significant delay of arthritis development of up to 12 months in seropositive RA-risk individuals. Here, we report our findings on patient-reported outcomes (PROs) in this study population., Methods: Seventy-eight RA-risk individuals were treated with one single dose of either placebo (PBO) or 1000 mg RTX plus 100 mg methylprednisolone (MP) and anti-histamines, regardless of treatment allocation, as co-medication. Data on quality of life were collected at baseline and 1, 4, 6, 12 and 24 months using established PRO questionnaires (visual analogue scale (VAS) pain, health assessment questionnaire disability index (HAQ-DI) score, EuroQol five dimension (EQ-5D) and both physical and mental component score of the 36-item short-form heath survey (SF-36))., Results: No significant changes in quality of life over a 2 year follow-up were observed in at-risk individuals treated with RTX compared to PBO given the PRO scores at 24 months (mean difference±SEM: HAQ score=0.07±0.16; EQ-5D=-0.02±0.05; VAS pain=11.11±7.40). Furthermore, no significant effect of treatment on perceived arthritis severity at the time of clinically manifest disease (arthritis) was found., Conclusion: One single dose of RTX plus MP administered to RA-risk individuals does not have a meaningful and measurable positive effect on PROs after 2 years of follow-up and/or perceived disease severity at the time of arthritis development., Trial Registration Number: Trial registered at EU Clinical Trial Register, EudraCT Number: 2009-010955-29 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=Prevention+of+RA+by+B+cell+directed+therapy)., Competing Interests: Competing interests: GF, SHMC, RBML, KIM, DMG, PPT, NdV and LGMvB report no conflict of interest. RFvV reports institutional grants from AstraZeneca, BMS, Galapagos, MSD, Novartis, Pfizer, Roche, Sanofi and UCB, as well as institutional fees from AbbVie, AstraZeneca, Biogen, BSM, Galapagos, GSK, Janssen, Pfizer, RemeGen and UCB, all outside the submitted work. SWT reports institutional grants from GSK, Lilly, Celgene, Pfizer, Roche, AstraZeneca, Galapagos, Citryll and Galvani bioelectronics, as well as institutional fees from NovoNordisk, Pfizer, AbbVie and UCB, all outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Uveitis is a common extra-musculoskeletal manifestation in Spondyloarthritis (SpA). The aim of this study was to analyze the prevalence of uveitis in SpA patients, its association with geographical areas and to determine whether its incidence was different before and after the biological era., Methods: ASAS-COMOSPA is a retrospective study that includes patients fulfilling ASAS SpA classification criteria from 22 countries. The overall prevalence of uveitis was calculated, and factors associated with the onset of a first episode of uveitis were evaluated using a Cox regression. A Log-Rank test was performed to compare the new onset of uveitis in the no biological era (SpA onset before 2000) vs biological era (SpA onset after 2000)., Results: 3984 patients were included. The likelihood of presenting a first uveitis episode increased over time, from a prevalence of 10.5% (95%CI 9.5%-11.4%) at the time of the SpA diagnosis to 46.6% (41.6%-51.5%) after 30 years since the SpA diagnosis. HLA-B27 positivity, family history of uveitis, peripheral enthesitis and IBD were associated with higher risk of uveitis. Patients with SpA disease onset after year 2000 showed a lower prevalence of uveitis compared with disease onset before year 2000 (8.2% vs 25.5%, p< 0.01), as well as a lower incidence (2.8 per 100 PY vs 6.1 per 100 PY, respectively)., Conclusion: In our study the risk of having suffered from at least one episode of uveitis ranged from 10% at the time of the diagnosis of axSpA to 47% after 30 years of disease duration. Patients with disease onset after biologic therapy introduction showed a significantly lower prevalence and incidence of first episodes of uveitis., (© 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.)

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory disease requiring long-term treatment. Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated tolerability and sustained clinical efficacy for up to 1 year for patients with PsA. Here, we report the longer-‍term safety and efficacy of bimekizumab up to 2 years., Methods: BE OPTIMAL (biologic disease-modifying antirheumatic drug [bDMARD]-naïve) and BE COMPLETE (prior inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi-IR]) assessed subcutaneous bimekizumab 160 mg every 4 weeks in patients with PsA. BE OPTIMAL included a reference arm (adalimumab 40 mg every 2 weeks); patients switched to bimekizumab at week 52 with no washout between treatments. BE OPTIMAL week 52 and BE COMPLETE week 16 completers were eligible for the BE VITAL open-label extension. Efficacy outcomes are reported to week 104/100 (BE OPTIMAL/BE COMPLETE)., Results: A total of 710/852 (83.3%) bDMARD-naïve and 322/400 (80.5%) TNFi-IR patients completed week 104/100. Up to 104 weeks, patients treated with bimekizumab in BE OPTIMAL and BE COMPLETE had treatment-emergent adverse event incidence rates (exposure-adjusted incidence rate/100 patient-years) of 179.9 (95% CI 166.9, 193.7) and 100.3 (89.2, ‍112.4), respectively. The proportion of patients achieving efficacy outcomes (≥ 50% improvement from baseline in American College of Rheumatology [ACR] response criteria, 100% improvement from baseline in Psorisis Area and Severity Index [PASI], minimal disease activity [MDA]) was sustained in all patients from week 52 to week 104/100., Conclusions: Bimekizumab was well tolerated for up to 2 years of treatment and no new safety signals were observed. Sustained clinical efficacy was observed up to 2 years in bDMARD-naïve and TNFi-IR patients with active PsA. Patients switching from adalimumab to bimekizumab demonstrated further improvement in skin and nail symptoms, and sustained efficacy in joint symptoms., Trial Registration: BE OPTIMAL (NCT03895203), BE COMPLETE (NCT03896581), BE VITAL (NCT04009499)., (© 2024. The Author(s).)

Ankylosing spondylitis (AS) is the historic term used for decades for the HLA-B27-associated inflammatory disease affecting mainly the sacroiliac joints (SIJ) and spine. Classification criteria for AS have radiographic sacroiliitis as a dominant characteristic. However, with the availability of MRI of SIJ, it could be demonstrated that the disease starts long before definite SIJ changes become visible on radiographs. The Assessment of SpondyloArthritis international Society, representing a worldwide group of experts reached consensus on changes in the nomenclature pertaining to axial spondyloarthritis (axSpA), such as the terminology of diagnosis and of assessment of disease activity tools. These are important changes in the field, as experts in axSpA are now in agreement that the term axSpA is the overall term for the disease. A further differentiation, of which radiographic versus non-radiographic is only one aspect, may be relevant for research purposes. Another important decision was that the terms AS and radiographic axSpA (r-axSpA) can be used interchangeably, but that the preferred term is r-axSpA. Based on the decision that axSpA is the correct terminology, a proposal was made to officially change the meaning of the ASDAS acronym to 'Axial Spondyloarthritis Disease Activity Score'. In addition, for simplification it was proposed that the term ASDAS (instead of ASDAS-CRP) should be preferred and applied to the ASDAS calculated with C reactive protein (CRP). It is hoped that these changes will be used consequently for education, in textbooks, manuscripts and presentations., Competing Interests: Competing interests: DvdH has received consulting fees from AbbVie, Argenx, Bayer, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer, Takeda, UCB Pharma. She is Director of Imaging Rheumatology bv, associate editor of ARD, editorial board member of J Rheumatol and RMD Open, advisor of ASAS. AM has received consulting fees from AbbVie, Amgen, BMS, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB Pharma and Viatris. SR has received research grants and/or consulting fees from AbbVie, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB, Sanofi. MD has received consulting fees from Pfizer, AbbVie, UCB, Amgen, BMS, Galapagos, Lilly, Novartis, Merck. FAvG has received consultation fees from Novartis, BMS, AbbVie, MSD, Janssen, Lily, UCB. LG has received research grants and/or consulting fees from AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, UCB. RDI has received consulting fees from Abbvie, Janssen, Novartis, UCB. RBML has received consulting fees from AbbVie, BMS, Galapagos, Eli-Lilly, Novartis, Jansen, Pfizer and UCB, is director of Rheumatology Consultancy BV and past-president and executive member of ASAS. HM-O has received grant support from Janssen, Novartis and UCB. Honoraria and/or speaker fees from AbbVie, Biogen, Eli-Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB. VN-C has received consultancy/speaker/research grants from Abbvie, BMS, Fresenius Kabi, Galapagos, Janssen, Lilly, Moonlake, MSD, Novartis, Pfizer, Roche, UCB. AP, Patient with AxSpa, Eupati Fellow, Patient Expert, Advocator, President of Cyprus League of People with Rheumatism, President of AGORA Federation, Secretary of Axial Spondylarthritis International Federation (ASIF), EULAR-Advocacy Committee Member-Pare Committee Member. DP has received research support from AbbVie, Eli Lilly, MSD, Novartis, Pfizer, consulting fees from AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer and UCB, and speaker fees from AbbVie, Canon, DKSH, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer and UCB. MP has received consulting fees from Novartis as well as support for attending meetings and/or travel from Abbvie, Jannsen, Novartis and UCB. MR has receieved consulting/speaker fees from Abbvie, Chugai, Boehringer, Eli-Lilly, Janssen, Novartis, UCB. PDS-B has received consulting/ speaker's fees from AbbVie, Celltrion, Eli Lilly, GSK, Janssen, Novartis, Pfizer and UCB. AS has received speaking and/or consulting fees from Abbvie, Novartis, UCB and Lilly. JS has received gees for consultancies and for being a member of speakers’ bureau from Abbvie, Merck, Novartis and UCB. FEVdB has received consulting fees from Abbvie, Amgen, Eli Lilly, Galapagos, Janssen, Moonlake, Novartis and UCB. IvdH-B has received consulting/speaker’s fees from UCB, Lilly, AbbVie, MSD, BMS, Novartis. PMM has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB. XB has received consulting/speaker’s fees Abbvie, Amgen, BMS, Chugai, Galapagos, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Zuellig Pharma and is Member of the Editorial Board of ARD, ASAS President and EULAR President Elect., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Biological- or targeted-synthetic DMARD-responses reported in randomized clinical trials, placebo-controlled or head-to-head, in patients with rheumatoid arthritis, psoriatic arthritis or spondyloarthritis are unbelievably similar, when looking across trials performed in the same disease and applying the same primary outcome measures. The exception to this rule may be the response to Janus-kinase-inhibitors, which seem to work 10 % better in all trials (JAK-bonus) This article provides a potential explanation for this remarkable phenomenon, including an explanation for the JAK-bonus. It seems as if JAK-inhibitors exert some inflammation-independent effects on pain, fatigue and wellbeing, and that drug treatment of rheumatic diseases is more than the inhibition of inflammation alone., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:RL received honoraria for participating in adboards of- or giving lectures for- AbbVie, Eli-Lilly, Galapagos, Jansen Pharma, Novartis, Pfizer and UCB.RL is owner of Rheumatology Consultancy BV, a small business under Dutch law., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose of Review: In recent years new recommendations have been published about organ assessment in the diagnosis of sarcoidosis., Recent Findings: Screening for pulmonary, cardiac, ocular, neurologic and renal involvement and hypercalcemia is recommended in the work-up for sarcoidosis, additionally, screening for hypercalciuria at the time of the diagnosis might be beneficial., Summary: One of the goals in the work-up of sarcoidosis is to assess the extent and severity of organ involvement. Timely and accurate assessment leads to determination of treatment indication. Screening for pulmonary involvement should include pulmonary imaging and pulmonary function tests. Screening for cardiac involvement should include a clear history including palpitations and collapse and a baseline electrocardiogram or 24-h Holter monitoring. At diagnosis, ophthalmological assessment is recommended. Furthermore, serum calcium level and serum creatinine level should be obtained. Although routine 24-h urinary calcium excretion is not included in the guidelines, performing this test routinely can be considered. On indication, neurologic, rheumatologic or dermatologic assessment can be performed., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Telemedicine is increasingly used in rheumatology. While telemedicine guaranteed care of patients during the COVID-19 pandemic, it is now increasingly used to facilitate triage of patients, monitoring of disease activity, and patients' education. In addition, tele-visits as well as remote physio- and psychotherapy are replacing traditional face-to-face contacts between patients and their healthcare provider. While this may save resources in a world in which the gap between the demand and the provision of healthcare increases, there is also a danger of losing essential information, for example by non-verbal communication, that can only be retrieved during face-to-face contact in the office. In addition, it may be challenging to build a trusting relationship between patients and healthcare professionals by virtual means only. Globally acting companies that see market opportunities already amply offer 'simple' technical solutions for telemedicine. While such solutions may seem (economically) interesting at first glance, there is a risk of monopolization, leaving the most valuable parts of healthcare to a small number of profit-seeking companies. In this article, the opportunities and threats of telemedicine in rheumatology are debated. A possible way forward is to complement traditional face-to-face visits with information gained by telemedicine, in order to render these consultations more efficient rather than replacing personal contact by technology., (© 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.)

Objectives: To quantify the additional value of a hypothetical biomarker predicting response to treatment for RA regarding efficacy and costs by using a modelling design., Methods: A Markov model was built comparing a usual care T2T strategy with a biomarker-steered strategy for RA patients starting biologic therapy. Outcome measures include time spent in remission or low disease activity (LDA) and costs. Four additional scenario analyses were performed by varying biomarker or clinical care characteristics: (i) costs of the biomarker; (ii) sensitivity and specificity of the biomarker; (iii) proportion of eligible patients tapering; and (iv) medication costs., Results: In the base model, patients spent 2.9 months extra in LDA or remission in the biomarker strategy compared with usual care T2T over 48 months. Total costs were €43 301 and €42 568 for, respectively, the usual care and biomarker strategy, and treatment costs accounted for 91% of total costs in both scenarios. Cost savings were driven due to patients in the biomarker strategy experiencing remission or LDA earlier, and starting tapering sooner. Cost-effectiveness was not so much driven by costs or test characteristics of the biomarker (scenario 1/2), but rather by the level of early and proactive tapering and drug costs (scenarios 3/4)., Conclusions: The use of a biomarker for prediction of response to b/tsDMARD treatment in RA can be of added value to current treat-to-target clinical care. However, gains in efficacy are modest and cost gains are depending on a combination of early proactive tapering and high medication costs., (© 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.)

Objectives: To define the instruments for the Assessment of SpondyloArthritis international Society-Outcomes Measures in Rheumatology (ASAS-OMERACT) core domain set for axial spondyloarthritis (axSpA)., Methods: An international working group representing key stakeholders selected the core outcome instruments following a predefined process: (1) identifying candidate instruments using a systematic literature review; (2) reducing the list of candidate instruments by the working group, (3) assessing the instruments' psychometric properties following OMERACT filter 2.2, (4) selection of the core instruments by the working group and (5) voting and endorsement by ASAS., Results: The updated core set for axSpA includes seven instruments for the domains that are mandatory for all trials: Ankylosing Spondylitis Disease Activity Score and Numerical Rate Scale (NRS) patient global assessment of disease activity, NRS total back pain, average NRS of duration and severity of morning stiffness, NRS fatigue, Bath Ankylosing Spondylitis Function Index and ASAS Health Index. There are 9 additional instruments considered mandatory for disease-modifying antirheumatic drugs (DMARDs) trials: MRI activity Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joints and SPARCC spine, uveitis, inflammatory bowel disease and psoriasis assessed as recommended by ASAS, 44 swollen joint count, Maastricht Ankylosing Spondylitis Enthesitis Score, dactylitis count and modified Stoke Ankylosing Spondylitis Spinal Score. The imaging outcomes are considered mandatory to be included in at least one trial for a drug tested for properties of DMARD. Furthermore, 11 additional instruments were also endorsed by ASAS, which can be used in axSpA trials on top of the core instruments., Conclusions: The selection of the instruments for the ASAS-OMERACT core domain set completes the update of the core outcome set for axSpA, which should be used in all trials., Competing Interests: Competing interests: VN-C: grants/honoraria from AbbVie, Janssen, Lilly, Novartis, Pfizer and UCB. ABoonen: grants from AbbVie ad Novartis and honoraria for boards or lectures form Abbvie, Galapagos and Lilly. PJM: research grants, consultation fees and/or speaker honoraria from Abbvie, Aclaris, Amgen, Bristol Myers, Boehringer-Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Lilly, Novartis, Pfizer, SUN Pharma and UCB. MD: consulting fees Pfizer, AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB Pharma. UK: grant and research support and consultancy fees from AbbVie, Amgen, Biogen, Chugai, Eli Lilly, Fresenius, Gilead, GSK, Janssen, MSD, Novartis, Pfizer, Roche and UCB. RBML: honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli-Lilly, Novartis, Pfizer and UCB Pharma; Director of Rheumatology Consultancy BV. XB: consulting fees AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB. WB-M: research speaker's fees from Janssen, Lilly, Novartis, Pfizer and Biopas. PC: research grants/honoraria from Novartis, Pfizer, Zuellig Pharma and Janssen. LF: employee and shareholder of Pfizer. MG-C: research collaboration with and provides services to Novartis Pharma AG. LG: research grants/honoraria from AbbVie, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer and UCB. BKE: consultancy, research grants and speaker's fees from AbbVie, Amgen, BMS, Eva, Hekma, Janssen, Lilly, MSD, New Bridge, Novartis, Pfizer, Roche, Sanofi‐Aventis and Servier. NH: consultant for Amgen, Abbvie, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB. PMM: consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript. WM: consulting fees Abbvie, BMS, Boehringer, Celgene, Lilly, Janssen, Novartis, Pfizer and UCB; research and/or educational grants from Abbvie, Novartis and Pfizer; Chief Medical Officer CARE Arthritis Limited. AM: speaker honoraria for lectures, presentations from Abbvie, UCB, Novartis, Pfizer, Gilead, Janssen, MSD, BMS, Biogen and Lilly. NdP: employee of UCB Pharma. DP: research support from AbbVie, Lilly, MSD, Novartis and Pfizer, consulting fees from AbbVie, Biocad, Gilead, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer, Samsung Bioepis and UCB and speaker fees from AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer and UCB. MP: speaker honoraria for lectures, presentations from Novartis and UCB. SR: research grants from Galapagos, MSD, Novartis and Pfizer and consulting fees from AbbVie, Eli Lilly, MSD, Novartis, UCB and Sanofi. I-HS: employee of AbbVie, Immunology Clinical Development, USA. DvdH: consulting fees AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology bv. ABoel, HD, YHK and SvW: no competing interests to declare., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: We aim to evaluate the clinical pharmacokinetics of a single dose interleukin-6 (IL-6) antibody tocilizumab (TCZ) in methylprednisolone (MP)-treated COVID-19 patients with cytokine storm syndrome (CSS)., Methods: MP pre-treated patients with COVID-19-associated CSS, defined as at least two elevations of C-reactive protein (CRP) >100 mg/L, ferritin >900 μg/L or D-dimers >1500 μg/L, received intravenous TCZ (8 mg/kg, max. 800 mg) upon clinical deterioration. A nonlinear-mixed effects model was developed based on TCZ serum concentrations and dosing information. Population pharmacokinetic parameters were estimated and concentration-time profiles were plotted against individual predicted values. Fixed dose simulations were subsequently performed based on the final model., Results: In total 40 patients (mean [SD] age: 62 [12] years, 20% female, body weight: 87 [17] kg) with COVID-19 induced CSS were evaluated on pharmacokinetics and laboratory parameters. A biphasic elimination of TCZ serum concentration was described by a homogeneous population pharmacokinetic model. Serum TCZ concentrations above the 1 μg/L target saturation threshold were covered for 16 days in all evaluated patients treated with a single dose of 8 mg/kg. In a simulation with TCZ 400 mg fixed dose, this condition of full IL-6 receptor occupancy at minimum serum concentration was also met., Conclusions: A single dose (8 mg/kg, max. 800 mg) is sufficient to cover a period of 16 days of IL-6-mediated hyperinflammation in COVID-19-induced CSS in MP-treated patients. Based on body weight PK simulations, a fixed-dose tocilizumab of 400 mg should be considered to prevent overtreatment, future drug shortage and unnecessary drug expenditure., (© 2023 British Pharmacological Society.)

Introduction: This exploratory analysis of FINCH 1 (NCT02889796) examined filgotinib (FIL) efficacy and safety in a subgroup of patients with rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX; MTX-IR) who had four poor prognostic factors (PPFs)., Methods: Patients with MTX-IR received placebo up to week (W)24 or FIL200 mg, FIL100 mg, or adalimumab up to W52; all received MTX. Efficacy and safety data were stratified by four PPFs versus fewer than four PPFs: seropositivity, high-sensitivity C-reactive protein (CRP) ≥ 6 mg/L, Disease Activity Score in 28 joints with CRP > 5.1, and erosions on X-rays., Results: At baseline, 687/1755 patients had four PPFs. At W12, whether with four PPFs or fewer than four PPFs, response rates on all American College of Rheumatology (ACR) measures were significantly greater with FIL200 and FIL100 versus placebo. At W52, FIL200 ACR20/50/70 response rates remained at least numerically higher versus adalimumab in both subgroups. At W52, FIL200 reduced modified total Sharp score (mTSS) change versus adalimumab in patients with four or fewer than four PPFs., Conclusions: In high-risk (four PPFs) patients with MTX-IR RA, FIL200 and FIL100 showed similar reductions in disease activity versus placebo at W12 as in patients with fewer than four PPFs. mTSS in patients receiving FIL200 changed little from W24 to W52, while that in patients receiving FIL100 progressed comparably to patients who received adalimumab. Tolerability was comparable across treatment arms and subgroups., (© 2022. The Author(s).)

Objectives: To evaluate the recapture of response with open-label (OL) ixekizumab (IXE) retreatment at week 104 in patients with axial spondyloarthritis who flared after withdrawal of IXE therapy., Methods: COAST-Y (NCT03129100) is a phase III extension study that included a double-blind, placebo-controlled, randomised withdrawal-retreatment period (RWRP). Patients who achieved remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 (inactive disease, ID) at least once at week 16 or 20 and <2.1 (low disease activity, LDA) at both visits) were randomised 2:1 at week 24 to continue IXE or withdraw to placebo. Patients who subsequently flared were switched to OL IXE every 2 or 4 weeks (Q2W or Q4W) at the next visit. The proportions of patients who recaptured ASDAS LDA and ID were summarised for those who experienced flare., Results: Of the 155 patients who entered the RWRP (placebo, n=53; IXE Q4W, n=48; IXE Q2W, n=54), 138 (89%) completed week 104. Of the placebo-treated patients (n=53), 28 (53%) experienced a flare during weeks 24-104; of these, 4 (14%) recaptured ASDAS LDA before retreatment with OL IXE, and 23 (82%) recaptured ASDAS LDA and 19 (68%) met ASDAS ID after retreatment. Of the continuously treated IXE patients (n=102), 13 experienced flare; 7 of 13 (54%) recaptured ASDAS LDA before switching to OL IXE retreatment, while 5 of 13 (38%) recaptured ASDAS LDA and 4 of 13 (31%) met ID after switching., Conclusions: Ninety-six per cent of patients withdrawn to placebo recaptured at least ASDAS LDA and 71% recaptured ASDAS ID with IXE retreatment at week 104. This may provide support to patients who may require a brief interruption in therapy., Competing Interests: Competing interests: RBML reports grants or contracts from AbbVie, Galapagos, Pfizer and UCB; personal fees from AbbVie, Celgene, Eli Lilly and Company, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB; consulting fees from Rheumatology Consultancy; and is a EULAR council member. DP reports grants or contracts from AbbVie, Eli Lilly and Company, MSD, Novartis and Pfizer; personal fees from AbbVie, Biocad, Eli Lilly and Company, Gilead, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Samsung Bioepis and UCB; and speaking fees and/or honoraria from AbbVie, Bristol Myers Squibb, Eli Lilly and Company, MSD, Novartis, Pfizer and UCB. PR reports research grants from Janssen and Novartis; speaking fees and/or honoraria from Abbott, AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis and Pfizer; travel support from Janssen; and participated on an advisory board for Abbott, AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis and Pfizer. FEVdB reports grant support from Merck and consulting fees from AbbVie, Amgen and Eli Lilly and Company. RB, SLL, JRL and SYP are employees of Eli Lilly and Company and own stock or stock options. LG reports grants or contracts from Novartis and Pfizer; personal fees from AbbVie, Galapagos, Janssen, Eli Lilly and Company, Pfizer, UCB and Galapagos; and participates in a leadership or fiduciary role in ACR, SPARTAN and ASAS., (© 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: To update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for management of rheumatoid arthritis (RA)., Methods: This systematic literature review (SLR) investigated the efficacy of conventional synthetic (cs), biological (b), biosimilar and targeted synthetic (ts)DMARDs in patients with RA. Medline, EMBASE, Cochrane CENTRAL and Web of Science were used to identify all relevant articles published since the previous update in 2019 to 14 January 2022., Results: Of 8969 search results, 169 articles were selected for detailed review and 47 were finally included. Trials investigated the efficacy of csDMARDs, bDMARDs and tsDMARDs, DMARD switching, tapering and trials investigating different treatment strategies. The compounds investigated were csDMARDs (methotrexate (MTX), leflunomide, sulfasalazine, hydroxychloroquine), bDMARDs (abatacept, adalimumab, certolizumab-pegol, denosumab, etanercept, infliximab, levilimab, olokizumab, opineracept, rituximab, sarilumab, tocilizumab) and tsDMARDs (baricitinib, filgotinib, tofacitinib, upadacitinib). The efficacy of csDMARDs+ short-term glucocorticoids in early RA was confirmed and similar to bDMARD+MTX combination therapy. Interleukin-6 pathway inhibition was effective in trials on olokizumab and levilimab. Janus kinase inhibitor (JAKi) was efficacious in different patient populations. After insufficient response to JAKi, patients could respond to TNFi treatment. Tapering of DMARDs was feasible for a proportion of patients, who were able to taper therapy while remaining in low disease activity or remission., Conclusion: The results of this SLR, together with one SLR on safety of DMARD and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA., Competing Interests: Competing interests: AK: Speakers bureau, Consultancy: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, Janssen, Merck Sharp and Dohme, Novartis, UCB and Pfizer. AS: received speaker/consulting fees from UCB, Novartis and Lilly. SAB: received an ASPIRE grant from Pfizer. JSS received grants from Abbvie, Astra-Zeneca, Janssen, Lilly, Novartis, Roche and honoraria from Abbvie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB. DvdH: received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma and is Director of Imaging Rheumatology bv. RC received consulting fees from Abbvie, BMS, Amgen, Celltrion, Eli-Lilly, Fresenius-Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB Pharma. CJE has received fees from Abbvie, Astra Zeneca, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Galapagos, GSK, Janssen, Eli Lilly, Pfizer, Roche, Sanofi for advisory boards, speakers bureau and research support. PV received consulting fees from Abbvie, BMS, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Pfizer, Sidekick Health, UCB and speaker's fees from Eli Lilly, Galapagos, MSD and Roularta and holds the Pfizer Chair Early RA Management at KU Leuven. JEP received research grants from AbbVie, Frensenius Kabi, Mallinckrodt Pharmaceuticals, Pfizer, Seattle Genetics and consulting fees from AbbVie, Amgen, Astra Zeneca, BI, BMS, Celltrion, EMERALD, Frensenius Kabi, Galapagos, GSK, Janssen, Lilly, Mallinckrodt Pharmaceuticals, Medexus, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Roche, Sandoz, Samsung, Sobi, Viatris. TT received grants from AbbVie, Asahikasei, AYUMI, Chugai, Eli Lilly Japan, Mitsubishi-Tanabe, Ono, and honoraria from AbbVie, Asahikasei, Astellas, Bristol-Myers Squibb, Chugai., Daiichi Sankyo., Eisai, Eli Lilly Japan, Gilead Sciences, Janssen K.K., Mitsubishi-Tanabe, Pfizer Japan. KLH received speaker’s fees from Abbvie and research grants from Pfizer and BMS. KLW received research grants from Pfizer, BMS, and GSK, and scientific consulting fees from UCB, Abbvie, BMS, Galapagos, Gilead, Lilly, GSK, Roche, and Novartis. DA received grants, speaker fees, or consultancy fees from Abbvie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, and Sobi. TAS has received grant/research support from AbbVie and Roche, has been a consultant for AbbVie and Sanofi Genzyme, and has been a paid speaker for AbbVie, Novartis, Roche, Sanofi, and Takeda. RBML: received consulting fees from AbbVie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Roche, UCB and is Director of Rheumatology Consultancy bv, (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objectives: To perform a systematic literature review (SLR) concerning the safety of synthetic(s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) to inform the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis (RA)., Methods: SLR of observational studies comparing safety outcomes of any DMARD with another intervention in RA. A comparator group was required for inclusion. For treatments yet without, or limited, registry data, randomised controlled trials (RCTs) were used., Results: Fifty-nine observational studies addressed the safety of DMARDs. Two studies (unclear risk of bias (RoB)) showed an increased risk of serious infections with bDMARDs compared with conventional synthetic (cs)DMARDs. Herpes zoster infections occurred more with JAKi than csDMARDs (adjusted HR (aHR): 3.66) and bDMARDs (aHR: 1.9-2.3) (four studies, two low RoB). The risk of malignancies was similar across bDMARDs (five studies) and with tofacitinib compared with bDMARDs (one study, low RoB). The risk of major adverse cardiovascular events (MACE) was similar with bDMARDs and tofacitinib (two studies, one low RoB). Thirty studies reported safety from RCTs, with one, designed to evaluate safety, showing that malignancies (HR (95% CI): 1.48 (1.04 to 2.09)) and MACE (HR (95% CI): 1.33 (0.91 to 1.94)) occurred numerically more frequently with tofacitinib (5 mg and 10 mg doses combined) than with TNFi in patients with cardiovascular risk factors. In this study, the risk of venous thromboembolism (VTE) was higher with tofacitinib 10 mg than with TNFi., Conclusion: The safety profile of bDMARDs was further demonstrated. Whether the difference in incidence of malignancies, MACE and VTE between tofacitinib and TNFi applies to other JAKi needs further evaluation., Competing Interests: Competing interests: AS: received speaker/consulting fees from UCB, Novartis and Lilly AK: Speakers bureau, Consultancy: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, Janssen, Merck Sharp and Dohme, Novartis, UCB und Pfizer SAB: received an ASPIRE grant from Pfizer JS received grants from Abbvie, Astra-Zeneca, Janssen, Lilly, Novartis, Roche and honoraria from Abbvie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB DvdH: received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma and is Director of Imaging Rheumatology bv RC received consulting fees from Abbvie, BMS, Amgen, Celltrion, Eli-Lilly, Fresenius-Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB Pharma. CJE Has received fees from Abbvie, Astra Zeneca, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Galapagos, GSK, Janssen, Eli Lilly, Pfizer, Roche, Sanofi for advisory boards, speakers bureau and research support PV received consulting fees from Abbvie, BMS, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Pfizer, Sidekick Health, UCB and speaker’s fees from Eli Lilly, Galapagos, MSD and Roularta. Holds the Pfizer Chair Early RA Management at KU Leuven. SdS: none JEP received research grants from AbbVie, Frensenius Kabi, Mallinckrodt Pharmaceuticals, Pfizer, Seattle Genetics and consulting fees from AbbVie, Amgen, Astra Zeneca, BI, BMS, Celltrion, EMERALD, Frensenius Kabi, Galapagos, GSK, Janssen, Lilly, Mallinckrodt Pharmaceuticals, Medexus, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Roche, Sandoz, Samsung, Sobi, Viatris TT received grants from AbbVie, Asahikasei, AYUMI, Chugai, Eli Lilly Japan, Mitsubishi-Tanabe, Ono, and honoraria from AbbVie, Asahikasei, Astellas, Bristol-Myers Squibb, Chugai., Daiichi Sankyo., Eisai, Eli Lilly Japan, Gilead Sciences, Janssen K.K., Mitsubishi-Tanabe, Pfizer Japan KLH: Honoraria from Abbvie (Speakers’ fees) and Research Grants from Pfizer and BMS KLW received research grants from Pfizer, BMS, and GSK, and scientific consulting fees from UCB, Abbvie, BMS, Galapagos, Gilead, Lilly, GSK, Roche, and Novartis DA received grants, speaker fees, or consultancy fees from Abbvie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, and Sobi TAS has received grant/research support from AbbVie and Roche, has been a consultant for AbbVie and Sanofi Genzyme, and has been a paid speaker for AbbVie, Novartis, Roche, Sanofi, and Takeda JWS: none RBML received consulting fees from AbbVie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Roche, UCB and is Director of Rheumatology Consultancy by JSS, DvdH, KLH, KLW, DA and RBML are members of the Editorial Board of ARD., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field., Methods: An international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item., Results: The task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3-6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations., Conclusions: These updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

This systematic literature review (SLR) regarding the efficacy, duration of use and safety of glucocorticoids (GCs), was performed to inform the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis (RA). Studies on GC efficacy were identified from a separate search on the efficacy of disease-modifying antirheumatic drugs (DMARDs). A combined search was performed for the duration of use and safety of GCs in RA patients. Dose-defined and time-defined GC treatment of any dose and duration (excluding intra-articular GCs) prescribed in combination with other DMARDs were considered. Results are presented descriptively. Two included studies confirmed the efficacy of GC bridging as initial therapy, with equal efficacy after 2 years of initial doses of 30 mg/day compared with 60 mg/day prednisone. Based on a recently performed SLR, in clinical trials most patients starting initial GC bridging are able to stop GCs within 12 (22% patients continued on GCs) to 24 months (10% patients continued on GCs). The safety search included 12 RCTs and 21 observational studies. Well-known safety risks of GC use were confirmed, including an increased risk of osteoporotic fractures, serious infections, diabetes and mortality. Data on cardiovascular outcomes were Inconsistent. Overall, safety risks increased with increasing dose and/or duration, but evidence on which dose is safe was conflicting. In conclusion, this SLR has confirmed the efficacy of GCs in the treatment of RA. In clinical trials, most patients have shown to be able to stop GCs within 12-24 months. Well-known safety risks of GC use have been confirmed, but with heterogeneity between studies., Competing Interests: Competing interests: SAB: received an ASPIRE grant from Pfizer. AS: received speaker/consulting fees from UCB, Novartis and Lilly. AK: Speakers bureau, Consultancy: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, Janssen, Merck Sharp and Dohme, Novartis, UCB und Pfizer. JWS: received grants from Abbvie, Astra-Zeneca, Janssen, Lilly, Novartis, Roche and honoraria from Abbvie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB. DvdH: received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma and is Director of Imaging Rheumatology bv. RC received consulting fees from Abbvie, BMS, Amgen, Celltrion, Eli-Lilly, Fresenius-Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB Pharma. CJE Has received fees from Abbvie, Astra Zeneca, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Galapagos, GSK, Janssen, Eli Lilly, Pfizer, Roche, Sanofi for advisory boards, speakers bureau and research support. PV received consulting fees from Abbvie, BMS, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Pfizer, Sidekick Health, UCB and speaker’s fees from Eli Lilly, Galapagos, MSD and Roularta. Holds the Pfizer Chair Early RA Management at KU Leuven. SdS: none. JEP received research grants from AbbVie, Frensenius Kabi, Mallinckrodt Pharmaceuticals, Pfizer, Seattle Genetics and consulting fees from AbbVie, Amgen, Astra Zeneca, BI, BMS, Celltrion, EMERALD, Frensenius Kabi, Galapagos, GSK, Janssen, Lilly, Mallinckrodt Pharmaceuticals, Medexus, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Roche, Sandoz, Samsung, Sobi, Viatris. TT received grants from AbbVie GK, Astellas, Asahi Kasei, Chugai, Daiichi Sankyo, Eisai, Takeda, Mitsubishi Tanabe, Nippon Kayaku, and speakers/consulting fees from AbbVie GK, Astellas, Chugai, Daiichi Sankyo, Eli Lilly Japan, Eisai, Gilead, Mitsubishi Tanabe, Pfizer Japan. KLH received speaker’s fees from Abbvie and research grants from Pfizer and BMS. KLW received research grants from Pfizer, BMS, and GSK, and scientific consulting fees from UCB, Abbvie, BMS, Galapagos, Gilead, Lilly, GSK, Roche, and Novartis. DA has received grants and/or speaker/consulting fees from Abbvie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, SoBi, Sanofi, Sandoz, and Roche. TAS has received grant/research support from AbbVie and Roche, has been a consultant for AbbVie and Sanofi Genzyme, and has been a paid speaker for AbbVie, Novartis, Roche, Sanofi, and Takeda. JSS: none. RBML: received consulting fees from AbbVie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Roche, UCB and is Director of Rheumatology Consultancy bv. JSS, DvdH, KLH, KLW, DD and RBML are members of the Editorial Board of ARD., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA)., Methods: Following the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting., Results: Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6-8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures., Conclusions: The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA., Competing Interests: Competing interests: SR received research grants from AbbVie, Galapagos, Novartis, Pfizer and UCB, and consulting fees from AbbVie, Eli Lilly, Novartis, MSD, Pfizer, UCB and Sanofi. EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, and Lilly, and holds research grants from Pfizer and Lilly. AS has received speaker/consulting fees from UCB and Novartis. AO has nothing to declare. CW has nothing to declare. XB received consulting fees and research grants from AbbVie, BMS, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB. XB is an editorial board member of Annals of Rheumatic Diseases. RBML received consulting fees from AbbVie, Bristol Myers Squibb, Celgene, Jansen, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and UCB, and is director of Rheumatology Consultancy. FEVdB received consulting and/or speaker fees from AbbVie, Amgen, Eli Lilly, Galapagos, Janssen, MoonLake, Novartis, Pfizer and UCB. BB has nothing to declare. AB has nothing to declare. PC received consulting/speaker’s fees from Eli Lilly, Pfizer, AbbVie, Sanofi, Galapagos, Fresenius Kabi, Biogen, MSD, UCB and Novartis. AC received honoraria for lectures from AbbVie, Merck Sharp & Dohme and Novartis. FAvG received grants from Stichting ASAS, and consulting/speaker’s fees from Novartis, UCB, Pfizer, AbbVie, Eli Lilly, Bristol Myers Squibb and Celgene. PG received speaker’s fees from AbbVie. LG received consulting fees and research grants from AbbVie, Eli Lilly, Galapagos, Janssen, MoonLake, Novartis, Pfizer and UCB. JH has received speaker honoraria and participated in advisory boards for AbbVie, Lilly, Novartis and Janssen. MdH has nothing to declare. MH has received speaker’s fees from Novartis. UK has received grant and research support and consultancy fees from AbbVie, Amgen, Biocad, Biogen, Chugai, Eli Lilly, Fresenius, Gilead, Grünenthal, GSK, Janssen, MSD, Novartis, Pfizer, Roche and UCB. CL-M has received speaker/consulting fees from UCB, Novartis, Janssen, Eli Lilly, MSD and AbbVie. PMM has received honoraria from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche, and UCB, and is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). HM-O received grants from Janssen, Novartis and UCB, and consultancy/speaker's fees from AbbVie, Biogen, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB. AM received research grants from UCB and consulting fees from AbbVie, Biogen, BMS, Eli Lilly, Gilead, Novartis, MSD, Pfizer and UCB. VN-C received grants/honoraria from AbbVie, Galapagos, Janssen, Lilly, MoonLake, Novartis, Pfizer and UCB. MJN received grant from Novartis and consultancy/speaker's fees from AbbVie, Eli Lilly, Janssen, Novartis and Pfizer. FMP-S received research grants from AbbVie, Janssen, and Novartis, and consulting fees from AbbVie, Bial, Biogen, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Pharma Kern, UCB and Tecnimed. DP received research support from AbbVie, Eli Lilly, MSD, Novartis, and Pfizer, and consulting fees from AbbVie, Biocad, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, MSD, MoonLake, Novartis, Pfizer, Samsung Bioepis, and UCB, and speaker's fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer and UCB. FP reports grants and personal fees from Novartis, Lilly and UCB, and personal fees from AbbVie, Amgen, BMS, Celgene, Janssen, Hexal, MSD, Pfizer and Roche. MR received consulting fees from AbbVie, Janssen, Eli Lilly, Novartis, Pfizer and UCB Pharma. MT has nothing to declare. SSZ has received consulting fees from UCB. NZ received research grants from AbbVie, Celgene, NewBridge and Pfizer; consulting fees from AbbVie, Eli Lilly, Pfizer, Gilead, Janssen, Novartis, NewBridge and Roche; and speaker's fees from AbbVie, Apotex, Eli Lilly, Janssen, Novartis, Pfizer, Pierre Fabre, Pharmaline, Roche and Sanofi-Aventis. DvdH received consulting fees from AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer and UCB Pharma, and is director of Imaging Rheumatology., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To update the evidence on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2022 update of the Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA., Methods: Systematic literature review (2016-2021) on efficacy and safety of bDMARDs in axSpA (radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)). Eligible study designs included randomised controlled trials (RCTs), strategy trials and observational studies (the latter only for safety and extra-musculoskeletal manifestations). All relevant efficacy/safety outcomes were included., Results: In total, 148 publications were included. Efficacy of golimumab and certolizumab was confirmed. Tumour necrosis factor inhibitor (TNFi) biosimilar-originator equivalence was demonstrated. RCT (n=15) data on efficacy of interleukin-17 inhibitors (IL-17i) demonstrated clinically relevant effects (risk ratio vs placebo to achieve ASAS40 response 1.3-15.3 (r-axSpA, n=9), 1.4-2.1 (nr-axSpA, n=2)). Efficacy of secukinumab/ixekizumab was demonstrated in TNFi-naïve and TNFi-inadequate responders. IL-23 and IL-12/23 inhibitors (risankizumab/ustekinumab) failed to show relevant benefits. Tapering of TNFi by spacing was non-inferior to standard-dose treatment. The first axSpA treat-to-target trial did not meet its primary endpoint, but showed improvements in secondary outcomes. No new risks were identified with TNFi use in observational studies (data lacking for IL-17i). Secukinumab (n=1) and etanercept (n=2) were associated with increased risk of uveitis in observational studies compared to monoclonal TNFi., Conclusions: New evidence supports the efficacy and safety of TNFi (originators/biosimilars) and IL-17i in r-axSpA and nr-axSpA, while IL-23i failed to show relevant effects. Observational studies are needed to confirm long-term IL-17i safety., Prospero Registration Number: CRD42021257588., Competing Interests: Competing interests: CW, AO and LF have nothing to declare. AS has received speaker/consulting fees from UCB and Novartis. XB received consulting fees and research grants from AbbVie, BMS, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB, and is an Editorial Board member of Annals of Rheumatic Diseases. RBML has received consulting fees from AbbVie, Bristol Myers Squibb, Celgene, Jansen, Galapagos, GlaxoSmithKline, Novartis, Pfizer and UCB, and is Director of Rheumatology Consultancy BV. SR received research grants from AbbVie, Galapagos, Novartis, Pfizer and UCB, and consulting fees from AbbVie, Eli Lilly, Novartis, MSD, Pfizer, UCB and Sanofi. DvdH received consulting fees from AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer and UCB Pharma, and is Director of Imaging Rheumatology BV. EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly and holds research grants from Pfizer and Lilly., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The first EULAR provisional recommendations on the management of rheumatic and musculoskeletal diseases (RMDs) in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), largely based on expert opinion, were published in June 2020. Since then, an unprecedented number of clinical studies have accrued in the literature. Several SARS-CoV-2 vaccines have been approved for population-wide vaccination programmes in EULAR-affiliated countries. Studies regarding vaccination of patients with (inflammatory) RMDs have released their first results or are underway.EULAR found it opportune to carefully review to what extent the initially consensus expert recommendations stood the test of time, by challenging them with the recently accumulated body of scientific evidence, and by incorporating evidence-based advice on SARS-CoV-2 vaccination. EULAR started a formal (first) update in January 2021, performed a systematic literature review according to EULAR's standard operating procedures and completed a set of updated overarching principles and recommendations in July 2021. Two points to consider were added in November 2021, because of recent developments pertaining to additional vaccination doses., Competing Interests: Competing interests: RBML received honoraria for lecturing and consultation from AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, UCB, is chair of EULAR’s committee for the quality of care and is owner and director of Rheumatology Consultancy BV. RBML is chair of EULAR’s committee of quality of care. AN received honoraria for lectures and consulting form BMS, UCB, Chigai and Roche. JWJB received honoraria for lectures and consulting from Fresnius, Galapagos, Syneos. GRB received honoraria for lectures and consulting from AbbVie, Amgen, BMS, Gilead, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis, Roche, UCB. RC received honoraria for lectures from AbbVie, Janssen, Roche, Sanofi. BC received honoraria for lecturing and consultation from AbbVie, BMS, Celltrion, Galapagos, Gilead, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Roche-Chugai. RC received honoraria for lectures and consulting or travel support from AbbVie, Janssen, Nordic Pharma, Roche and Sanofi. JRC received research grants and consulting from Amgen, AbbVie, BMS, GSK, Janssen, Lilly, Novartis, Pfizer, and chairs the ACR COVID Vaccine Guidance Task Force. OE received honoraria for lecturing and consultation from AbbVie, BMS, Celgene, Gilead, Janssen, Eli Lilly, Novartis, Pfizer and B.I. MWH Consultation and speaker’s fees from ALK and Roche. LH received a speaker’s fee from Grünenthal, honoraria for writing articles from MedMedia, and travel support from AbbVie, Biogen, BMS, MSD, Novartis and Roche. AI received consultancies, honoraria, speaker-fees from AbbVie, MSD, Alfasigma, Celltrion, BMS, Celgene, Eli Lilly, Sanofi, Genzyme, Pfizer, Galapagos, Gilead, Novartis, SOBI and research grants from MSD, Alfasigma, AbbVie. AI is acting president of EULAR. JDI received research grants from Pfizer, Janssen and GSK and honoraria for lectures, conference support from Eli Lilly and Gilead, and speaker/consulting fees from AbbVie, Gilead, Roche and UCB. XM received consulting fees from BMS, Gilead, Janssen, Pfizer, Samsung, UCB. BC received honoraria from AbbVie, BMS, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB; and research grants from Novartis, Pfizer, and Roche. IBM received research grants from Lilly, Pfizer, BMS, Celgene, Janssen; and consulting fees from AbbVie, BMS, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis and UCB. IBM is past president of EULAR. HS-K received honoraria for lectures and consulting from AbbVie, Amgen, BMS, Gilead, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis, Roche and UCB. JSS received grants to his institution from AbbVie, AstraZeneca, Janssen, Lilly, MSD, Pfizer and Roche and provided expert advice for, or had symposia speaking engagements with, AbbVie, Amgen, AstraZeneca, Astro, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO Pharma, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi and UCB. JSS is editor of the Annals of Rheumatic Diseases. KW received honoraria and consultancy fees from AbbVie, Lilly, Roche, GSK, Novartis, BMS, Pfizer, UCB, Janssen, Regeneron and Sanofi. VN-C received research grants/honoraria from AbbVie, Janssen, Lilly, Novartis, Pfizer, and UCB. PMM received consulting/speaker’s fees from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this manuscript., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: As first-degree relatives (FDRs) of HLA-B27-positive patients with axial spondyloarthritis (SpA) have an increased risk of developing axial SpA, the objectives were 1) to evaluate the presence of highly specific imaging features as well as clinical signs of SpA at baseline and after 1 year of follow-up, and 2) to describe the evolution toward clinical disease within 1 year of follow-up in a cohort of seemingly healthy FDRs of HLA-B27-positive axial SpA patients., Methods: The Pre-SpA cohort is a 5-year prospective inception cohort of seemingly healthy FDRs of HLA-B27-positive axial SpA patients. Clinical and imaging features were collected and recorded., Results: At baseline, 19% of the FDRs reported inflammatory back pain, 32% current arthralgia, 3% arthritis (ever), 5% enthesitis (ever), and 1% dactylitis (ever), and 3% had an extraarticular manifestation. C-reactive protein level was elevated in 16%, and erythrocyte sedimentation rate was elevated in 7%. On magnetic resonance imaging (MRI) views of sacroiliac joints, 10% had a Spondyloarthritis Research Consortium of Canada score of ≥2, 4% had a score of ≥5, and 4% had deep lesions. In total, 1% fulfilled the modified New York criteria for radiographic sacroiliitis. Clinical, MRI, and acute phase findings were equally distributed between HLA-B27-positive and -negative FDRs. After 1 year of follow-up, clinical parameters did not change on the group level, but 6% of the FDRs were clinically diagnosed with axial SpA, of whom 86% were HLA-B27-positive., Conclusion: Features associated with SpA or imaging abnormalities were found in up to 32% of seemingly healthy FDRs, with an equal distribution between HLA-B27-positive and -negative FDRs. Progression to clinical axial SpA within 1 year of follow-up was mainly observed in HLA-B27-positive FDRs., (© 2021 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: In radiographic axial spondyloarthritis (r-axSpA), spinal damage manifests as syndesmophytes and facet joint ankylosis (FJA). We evaluated whether the presence of one lesion increased the risk of the other lesion., Methods: Patients with r-axSpA underwent low-dose CT (ldCT) and MRI of the whole spine at baseline and 2 years. On ldCT, vertebrae were scored for presence and size of syndesmophytes; facet joints were assessed for ankylosis. MR images were assessed for inflammation. Two hypotheses were tested: (i) presence of FJA is associated with new syndesmophyte(s) on the same vertebral unit (VU) 2 years later, and (ii) presence of bridging syndesmophyte(s) is associated with new FJA on the same VU 2 years later. Two generalized estimating equations models were tested per hypothesis using increase of FJA/syndesmophytes (model A) or presence of FJA/syndesmophytes (model B) as outcome, adjusted for inflammation at baseline. Secondary analyses tested the hypotheses with outcomes on adjacent VUs and dose-response effects., Results: Fifty-one patients were included (mean age 49, 84% male, 82% HLA-B27+). Baseline bridging syndesmophytes occurred more often (range: 10-60% per VU) than FJA (range: 8-36%). Odds ratios (ORs) (95% CI) for presence of bridging syndesmophytes on development of FJA were 3.55 (2.03, 6.21) for model A and 3.30 (2.14, 5.09) for model B. ORs for presence of baseline FJA on new syndesmophytes were 1.87 (1.20, 2.92) for model A and 1.69 (0.88, 3.22) for model B. Secondary analyses yielded positive ORs for both hypotheses., Conclusions: Bone formation in vertebrae and in facet joints influence each other's occurrence, with the effect of syndesmophytes being larger than that of FJA., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Comparing treatment effectiveness over time in observational settings is hampered by several major threats, among them confounding and attrition bias., Objectives: To develop European Alliance of Associations for Rheumatology (EULAR) points to consider (PtC) when analysing and reporting comparative effectiveness research using observational data in rheumatology., Methods: The PtC were developed using a three-step process according to the EULAR Standard Operating Procedures. Based on a systematic review of methods currently used in comparative effectiveness studies, the PtC were formulated through two in-person meetings of a multidisciplinary task force and a two-round online Delphi, using expert opinion and a simulation study. Finally, feedback from a larger audience was used to refine the PtC. Mean levels of agreement among the task force were calculated., Results: Three overarching principles and 10 PtC were formulated, addressing, in particular, potential biases relating to attrition or confounding by indication. Building on Strengthening the Reporting of Observational Studies in Epidemiology guidelines, these PtC insist on the definition of the baseline for analysis and treatment effectiveness. They also focus on the reasons for stopping treatment as an important consideration when assessing effectiveness. Finally, the PtC recommend providing key information on missingness patterns., Conclusion: To improve the reliability of an increasing number of real-world comparative effectiveness studies in rheumatology, special attention is required to reduce potential biases. Adherence to clear recommendations for the analysis and reporting of observational comparative effectiveness studies will improve the trustworthiness of their results., Competing Interests: Competing interests: DSC has received consulting fees from Abbvie, MSD, and Pfizer outside submitted work. KL has received speaker fees from Gilead-Galapagos and grant/research support from AbbVie outside submitted work. ZR has received consulting and speaker fees from Abbvie, Eli Lilly, Novartis, MSD, Pfizer, Roche, Sandoz outside submitted work. PMM has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, unrelated to the work presented in this manuscript, and is supported by the National Institute for Health Research (NIHR), University College London Hospitals (UCLH), Biomedical Research Centre (BRC). Disclaimer: The views expressed here are those of the authors and do not necessarily represent the views of the (UK) National Health Service (NHS), the National Institute for Health Research (NIHR), or the (UK) Department of Health, or any other organisation. FI has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, SOBI, Roche and UCB, unrelated to the work presented in this manuscript. TAS has received grant/research support from AbbVie and Roche, has been a consultant for AbbVie and Sanofi Genzyme, and has been a paid speaker for AbbVie, Roche, Sanofi and Takeda. AF has received grant/research support from AbbVie, BMS, Eli-Lilly, Galapagos, and Pfizer, has been a paid speaker for AbbVie, BMS, Eli-Lilly, Novartis, on Novartis. MdW operating for Stichting Tools has received fees for lectures or consultancy provided by MdW from Celgene, Eli Lilly, Pfizer and UCB, over the last three years, unrelated to the work presented in this manuscript. AS has received speaker’s fees from AbbVie, BMS, Celltrion, MSD, Pfizer, and Roche, unrelated to the work presented in this manuscript. SRS has received consulting/speaker’s fees from 67 Health, Ampersand Health, Envision Pharma Group, Janssen and On The Pulse Consultancy, and is an employee of Envision Pharma Group, unrelated to the work presented in this manuscript. LMØ has received grant/research support from Novartis, unrelated to the work presented in this manuscript., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Perform a systematic literature review (SLR) on risk and prognosis of SARS-CoV-2 infection and vaccination against SARS-CoV-2 in patients with rheumatic and musculoskeletal diseases (RMDs)., Methods: Literature was searched up to 31 May 2021, including (randomised) controlled trials and observational studies with patients with RMD. Pending quality assessment, data extraction was performed and risk of bias (RoB) was assessed. Quality assessment required provision of (1) an appropriate COVID-19 case definition, and (2a) a base incidence (for incidence data) or (2b) a comparator, >10 cases with the outcome and risk estimates minimally adjusted for age, sex and comorbidities (for risk factor data)., Results: Of 5165 records, 208 were included, of which 90 passed quality assessment and data were extracted for incidence (n=42), risk factor (n=42) or vaccination (n=14). Most studies had unclear/high RoB. Generally, patients with RMDs do not face more risk of contracting SARS-CoV-2 (n=26 studies) or worse prognosis of COVID-19 (n=14) than individuals without RMDs. No consistent differences in risk of developing (severe) COVID-19 were found between different RMDs (n=19). Disease activity is associated with worse COVID-19 prognosis (n=2), possibly explaining the increased risk seen for glucocorticoid use (n=13). Rituximab is associated with worse COVID-19 prognosis (n=7) and possibly Janus kinase inhibitors (n=3). Vaccination is generally immunogenic, though antibody responses are lower than in controls. Vaccine immunogenicity is negatively associated with older age, rituximab and mycophenolate., Conclusion: This SLR informed the July 2021 update of the European Alliance of Associations for Rheumatology recommendations for the management of RMDs in the context of SARS-CoV-2., Competing Interests: Competing interests: RBML received honoraria for lecturing and consultation from AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Eli Lilly, Novartis, Pfizer and UCB and is the owner and director of Rheumatology Consultancy BV. PMM received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this manuscript, and is supported by the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the (UK) National Health Service, the NIHR or the (UK) Department of Health. VN-C received research grants/honoraria from AbbVie, Janssen, Lilly, Novartis, Pfizer and UCB., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Analyses of lymphoid organs are required to further elucidate the pathogenesis of inflammatory diseases like rheumatoid arthritis (RA). Yet, invasive tissue collection methods are scarcely applied, because they are often considered burdensome, although patients do not always consider invasive methods as a high burden. We aimed to investigate the perspectives of study participants undergoing ultrasound-guided inguinal lymph node (LN) needle biopsy sampling and determine the molecular and cellular quantity and quality of LN biopsies., Methods: Together with patient research partners, questionnaires were developed to evaluate the motives, expectations, and experiences of participants undergoing a LN biopsy. Healthy controls and RA(-risk) patients were asked to complete these questionnaires before and after the procedure. RNA and lymphocyte yields from obtained LN biopsies were also calculated., Results: We included 50 individuals, of which 43 (86%) reported their pre- and post-procedure experiences. The median reported pain on a 5-point Likert scale (1 not to 5 very painful) was 1. Interestingly, almost all (n = 32; 74%) study participants would undergo a second procedure and more than half (n = 23; 54%) would encourage others to take part in the LN biopsy study. Motives for current and future participation were mostly altruistic. Inguinal hematoma occurred frequently, but no other significant or unexpected complications ensued. The LN biopsies yielded sufficient and high-quality RNA and lymphocyte numbers., Conclusions: Ultrasound-guided inguinal LN biopsy sampling is well-tolerated, safe, and provides sufficient material for further molecular and cellular analyses. Our participants' positive experiences endorse the application of this research tool to further elucidate the pathogenesis of RA and other inflammatory diseases., (© 2022. The Author(s).)

Objective: To investigate determinants of the physician global assessment (PhGA) of disease activity and the influence of the contextual factors on this relationship in patients with early axial spondyloarthritis (SpA)., Methods: Five-year data of DESIR, a cohort of early axial SpA, were analyzed. Univariable generalized estimating equations (GEEs) were used to investigate contributory explanatory effects of various potential determinants of PhGA. Effect modification by contextual factors (age, sex, and educational level) was tested, and if significant, models were stratified. Autoregressive GEE models (i.e., models adjusted for PhGA at the previous time point) were used to confirm a longitudinal relationship., Results: A total of 708 patients were included. Higher Bath Ankylosing Spondylitis Disease Activity Index individual questions, swollen joint count in 28 joints (SJC28), tender joint count in 53 joints, Maastricht Ankylosing Spondylitis Enthesitis Score, C-reactive protein (CRP) level, and Bath Ankylosing Spondylitis Metrology Index score were associated with a higher PhGA. Sex and age were effect modifiers of SJC28; the contributory effect of SJC28 was largest in the younger male stratum (β = 1.07 [95% confidence interval (95% CI) 0.71, 1.43]), and the smallest in the older female stratum (β = 0.13 [95% CI 0.04, 0.22]). Autoregressive GEE models revealed the same determinants as having a longitudinal association with PhGA and the same pattern of effect modification., Conclusion: Patients' subjective symptoms, peripheral arthritis and enthesitis, higher CRP level, and impaired spinal mobility contribute to explaining PhGA in patients with early axial SpA, irrespective of sex and age. Intriguingly, physicians consider the presence of swollen joints as more important in males than in females., (© 2020 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)