Search

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.

ObjectivesInflammatory rheumatic and musculoskeletal diseases (iRMDs) are associated with increased systemic bone loss that is mediated by chronic inflammation, treatment with glucocorticoids (GCs) and other factors. Our objective was to analyse the impact of variables that influence osteoporosis (OP) in patients with iRMD treated with GC.MethodsRh-GIOP (acronyme) is a prospective observational cohort study investigating bone health in consecutive patients with iRMD and current or prior GC treatment. We present an analysis of the patients’ baseline data here. Bone mineral density (BMD) measured by dual X-ray absorptiometry was the primary outcome. Multivariable linear regression models were performed to identify variables associated with BMD.ResultsData from 1066 patients with iRMD were analysed. GC doses of 7.5 mg/day showed a negative association with BMD overall, but this effect seemed to be specific only to patients with moderate or high disease activity (Disease Activity Score 28–C reactive protein >3.2).ConclusionsGCs of ≤5 mg/day did not seem to be associated with a reduction of BMD in patients with iRMD and current or prior exposure to GC. This is most likely due to the dampening of inflammation by GC, which exerts a mitigating effect on the risk of OP. In RA, current GC doses of >7.5 mg/day were negatively associated with BMD, but only in patients with moderate to high disease activity.Trial registration numberNCT02719314.

ObjectiveTo investigate the potential of whole-body positron emission tomography/computed tomography (PET/CT) with a macrophage tracer to image arthritis in patients with early rheumatoid arthritis (RA).MethodsThirty-five previously untreated, clinically active patients with early RA underwent whole-body PET/CT scanning with the macrophage tracer (R)-[11C]PK11195 in addition to clinical assessment (Disease Activity Score in 44 joints [DAS44]). Tracer uptake was assessed quantitatively as standardized uptake values (SUVs). In addition, 2 readers blinded to clinical assessment visually scored tracer uptake in joints. Clinical and PET variables were compared using Cohen , linear regression/correlation, and t tests, where appropriate.ResultsAll but 1 patient showed enhanced tracer uptake in at least 1 joint. Twelve percent of all joints (171/1470) were visually positive on the PET scan, most frequently the small joints in feet (40%) and hands (37%), followed by wrists (15%). Correlations of visual scores with clinical findings both at patient and joint levels were absent or weak. In contrast, average SUVs in the hands, feet, and whole body showed significant correlations with DAS44 scores, with the best correlation seen in the feet (R2 = 0.29, P < 0.01).ConclusionClinically active patients with early RA had increased joint uptake of a macrophage PET tracer, especially in the feet. Quantitative, but not visual PET measures of whole body and joint groups, particularly the feet, showed moderate and statistically significant correlations with clinical outcome.

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 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/.

Background/Aims The combined use of Power Doppler and B-mode ultrasound (PDUS) allows visualisation of morphological and pathophysiological changes of the synovium. ULTIMATE (NCT02662985) was the first large, randomised, double-blind, placebo-controlled PDUS phase IIIb study in psoriatic arthritis (PsA) to demonstrate that the validated Global OMERACT EULAR Synovitis Score (GLOESS), an ultrasound score at patient level, could detect the early and continuous decrease in synovitis in a multicentre setting using different ultrasound devices and examiners. Since the ultrasound assessment for GLOESS is time-consuming owing to the number of joints assessed, we investigated the ability of various reduced joint sets to predict GLOESS. Methods ULTIMATE was a 52-week study of secukinumab with a 12-week, double-blind, placebo-controlled period followed by a 12-week, open-label treatment period and 6-month open-label extension period. GLOESS for 24 paired joints was calculated, with a resultant potential score ranging from 0 to 144. Based on their composite PDUS scores, highly correlated joint clusters were identified with a Spearman’s rank correlation matrix and a Clustered Image Map. Representative joints were then selected from each group by various approaches (best correlation, model optimisation, etc.) yielding several joint combinations. For these reduced joint sets, GLOESS was predicted with linear models based on data from 60% of randomly selected patients from ULTIMATE. The remaining 40% of patient data were used for model validation and diagnostics. Results Five models were established with reduced pairs of joint sets (9-13 pairs) for PDUS-detected synovitis. The joints included in each linear model are summarised in the Table. All five reduced joint set models demonstrated scores very close to full 48 joint GLOESS (R2 ∼0.95); models 1-3 (based on 9 joint pairs) were less accurate at predicting GLOESS than models 4 and 5 (based on 13 and 12 joint pairs, respectively) for the secukinumab cohort in the open-label part (data to be shown in poster). Conclusion All models of reduced joint sets for PDUS-detected synovitis predicted GLOESS well. The next steps will be to document responsiveness and ability to discriminate between active and placebo treatment. Disclosure P.G. Conaghan: Consultancies; P.G.C. has received consultancy fees from AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Janssen, Merck, Novartis and Pfizer, Stryker and UCB. Member of speakers’ bureau; P.G.C. has received speakers bureau fees from AbbVie, Novartis and Pfizer. M. D'agostino: Consultancies; M.A.D'A. has received consultancy fees from AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Roche, Sanofi, and UCB. Member of speakers’ bureau; M.A.D'A. has received speakers bureau fees from AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Roche, Sanofi and UCB. M. Boers: Consultancies; M.B. has received consultancy fees from Novartis. E. Naredo: Honoraria; E.N. has received honoraria for clinical trials from AbbVie, BMS and Novartis. Member of speakers’ bureau; E.N. has received speakers bureau fees from AbbVie, BMS, Celgene GmbH, Janssen, Lilly, Novartis, Pfizer, Roche and UCB. Grants/research support; E.N. has received research grants from Eli Lilly. P. Mandl: Member of speakers’ bureau; P.M. has received speakers bureau fees from AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche and UCB. Grants/research support; P.M. has received grant/research support from AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche and UCB. P. Carron: Consultancies; P.C. has received consultancy fees from AbbVie, Bristol Myers Squibb, Celgene Corporation, Eli Lilly, Gilead, Merck Sharp Dohme, Novartis, Pfizer and UCB. Member of speakers’ bureau; P.C. has received speakers bureau fees from AbbVie, Bristol Myers Squibb, Celgene Corporation, Eli Lilly, Gilead, Merck Sharp Dohme, Novartis, Pfizer and UCB. Grants/research support; P.C. has received grant/research support from Merck Sharp Dohme, Pfizer and UCB. M. Backhaus: Consultancies; M.B. has received consultancy fees from BMS, Galapagos, Jonsson, MSD, Novartis, Pfizer, Roche and UCB. Member of speakers’ bureau; M.B. has received speakers bureau fees from BMS, Galapagos, Jonsson, MSD, Novartis, Pfizer, Roche and UCB. Grants/research support; M.B. has received grant/research support from BMS, Galapagos, Jonsson, MSD, Novartis, Pfizer, Roche and UCB. A. López-Rodríguez: Consultancies; A.L.R. has received consultancy fees from Eli Lilly, GSK, Janssen, Novartis, Roche and UCB. Member of speakers’ bureau; A.L.R. has received speakers bureau fees from Eli Lilly, GSK, Janssen, Novartis, Roche and UCB. P. Hanova: Consultancies; P.H. has received consultancy fees from Novartis. P. Goyanka: Other; P.G. is an employee of Novartis. B.G. Sahoo: Other; B.G.S. is an employee of Novartis. C. Gaillez: Shareholder/stock ownership; C.G. is a shareholder of Novartis and BMS. Other; C.G. is an employee of Novartis. W. Bao: Shareholder/stock ownership; W.B. is a shareholder of Novartis. Other; W.B. is an employee of Novartis.

Core outcome sets are critically important outcomes that should be measured in clinical trials. Their absence in atopic dermatitis is a form of research waste and impedes combining evidence to inform patient care. Here, we articulate the rationale for core outcome sets in atopic dermatitis and review the work of the international Harmonising Outcome Measures for Eczema group from its inception in Munich, 2010. We describe core domain determination (what should be measured), to instrument selection (how domains should be measured), culminating in the complete core outcome measurement set in Tokyo, 2019. Using a "road map," Harmonising Outcome Measures for Eczema includes diverse research methods including Delphi and nominal group techniques informed by systematic reviews of properties of candidate instruments. The 4 domains and recommended instruments for including in all clinical trials of atopic dermatitis are patient symptoms, measured by Patient-Oriented Eczema Measure and peak Numerical Rating Scale 11 for itch intensity over 24 hours, clinical signs measured using the Eczema Area and Severity Index, quality of life measured by the Dermatology Life Quality Index series for adults, children, and infants, and long-term control measured by either Recap of atopic eczema or Atopic Dermatitis Control Tool. Published version Details of funding for each of the consensus meetings is outlined in the published meeting reports. The following additional funding sources contributed to facilitating the HOME COS development: National Institute for Health and Care Research Senior Investigator award to Prof Hywel Williams (RE 2374) funded travel costs to enable UK patients to participate in HOME meetings; National Institute for Health and Care Research Programme Grant for Applied Research RP-PG-0407-10177 ‘‘Setting Priorities and Reducing Uncertainties for the Prevention and Treatment of Skin Disease (SPRUSD)’’ was used to support completion of the some of the systematic reviews, the cost of meetings and patient and public involvement (Prof Kim Thomas); NIH NIAMS A Community-based Assessment of Skin Care, Allergies, and Eczema: The CASCADE Trial grant number 5 R01 AR071057-05 and Oregon Clinical and Translational Research Institute (OCTRI) assisted with outcome evaluations and associated travel costs (Prof Eric Simpson); Laura Howells received a PhD studentship from the British Skin Foundation (Ref: 8016) for studies that informed this work.

Contains fulltext : 251784.pdf (Publisher’s version ) (Closed access) BACKGROUND: Concerns have been raised regarding the risks of SARS-CoV-2 breakthrough infections in vaccinated patients with immune-mediated inflammatory diseases treated with immunosuppressants, but clinical data on breakthrough infections are still scarce. The primary objective of this study was to compare the incidence and severity of SARS-CoV-2 breakthrough infections between patients with immune-mediated inflammatory diseases using immunosuppressants, and controls (patients with immune-mediated inflammatory diseases not taking immunosuppressants and healthy controls) who had received full COVID-19 vaccinations. The secondary objective was to explore determinants of breakthrough infections of the delta (B.1.617.2) variant of SARS-CoV-2, including humoral immune responses after vaccination. METHODS: In this substudy, we pooled data collected in two large ongoing prospective multicentre cohort studies conducted in the Netherlands (Target to-B! [T2B!] study and Amsterdam Rheumatology Center COVID [ARC-COVID] study). Both studies recruited adult patients (age ≥18 years) with immune-mediated inflammatory diseases and healthy controls. We sourced clinical data from standardised electronic case record forms, digital questionnaires, and medical files. We only included individuals who were vaccinated against SARS-CoV-2. For T2B!, participants were recruited between Feb 2 and Aug 1, 2021, and for ARC-COVID, participants were recruited between April 26, 2020, and March 1, 2021. In this study we assessed data on breakthrough infections collected between July 1 and Dec 15, 2021, a period in which the delta SARS-CoV-2 variant was the dominant variant in the Netherlands. We defined a SARS-CoV-2 breakthrough infection as a PCR-confirmed or antigen test-confirmed SARS-CoV-2 infection that occurred at least 14 days after vaccination. All breakthrough infections during this period were assumed to be due to the delta variant due to its dominance during the study period. We analysed post-vaccination serum samples for anti-receptor binding domain (RBD) antibodies to assess the humoral vaccination response (T2B! study only) and anti-nucleocapsid antibodies to identify asymptomatic breakthrough infections (ARC-COVID study only). We used multivariable logistic regression analyses to explore potential clinical and humoral determinants associated with the odds of breakthrough infections. The T2B! study is registered with the Dutch Trial Register, Trial ID NL8900, and the ARC-COVID study is registered with Dutch Trial Register, trial ID NL8513. FINDINGS: We included 3207 patients with immune-mediated inflammatory diseases who receive immunosuppressants, and 1807 controls (985 patients with immune-mediated inflammatory disease not on immunosuppressants and 822 healthy controls). Among patients receiving immunosuppressants, mean age was 53 years (SD 14), 2042 (64%) of 3207 were female and 1165 (36%) were male; among patients not receiving immunosuppressants, mean age was 54 years (SD 14), 598 (61%) of 985 were female and 387 (39%) were male; and among healthy controls, mean age was 57 years (SD 13), 549 (67%) of 822 were female and 273 (33%) were male. The cumulative incidence of PCR-test or antigen-test confirmed SARS-CoV-2 breakthrough infections was similar in patients on immunosuppressants (148 of 3207; 4·6% [95% CI 3·9-5·4]), patients not on immunosuppressants (52 of 985; 5·3% [95% CI 4·0-6·9]), and healthy controls (33 of 822; 4·0% [95% CI 2·8-5·6]). There was no difference in the odds of breakthrough infection for patients with immune-mediate inflammatory disease on immunosuppressants versus combined controls (ie, patients not on immunosuppressants and healthy controls; adjusted odds ratio 0·88 [95% CI 0·66-1·18]). Seroconversion after vaccination (odds ratio 0·58 [95% CI 0·34-0·98]; T2B! cohort only) and SARS-CoV-2 infection before vaccination (0·34 [0·18-0·56]) were associated with a lower odds of breakthrough infections. INTERPRETATION: The incidence and severity of SARS-CoV-2 breakthrough infections in patients with immune-mediated inflammatory diseases on immunosuppressants was similar to that in controls. However, caution might still be warranted for those on anti-CD20 therapy and those with traditional risk factors. FUNDING: ZonMw (the Netherlands Organization for Health Research and Development) and Reade foundation.

Purpose of review Glucocorticoids justifiably remain a cornerstone in the treatment of many inflammatory rheumatic diseases but many are opposed to their use because of the side effects, most of them known to be dose-dependent. Most concerns regarding glucocorticoids stem from observational studies which are affected by several forms of bias, mainly confounding by indication, that may result in overestimation of harm. Solid evidence regarding the safety of low-dose glucocorticoids remains remarkably scarce. Recent findings Several observational studies showed heterogeneous results and two 6-month trials showed no increase of harm. The GLORIA trial of 5mg/day prednisolone vs. placebo in patients aged 65þ is the first randomized control trial with glucocorticoids safety as coprimary outcome. The benefits of glucocorticoids in terms of symptoms and structural damage were confirmed, but the proportion of patients with at least one adverse event of special interest (serious or glucocorticoids-related) was increased by 24%, mostly due to nonsevere infections. Summary Based on current evidence the benefit-risk balance of low-dose glucocorticoids in rheumatoid arthritis, and probably in other rheumatic diseases is generally favourable. Physicians should be aware of the risks and mitigate them, but avoid the negative effects of unfounded fear.

ObjectivesThe aim of this study was to assess the safety and efficacy of long-term low-dose glucocorticoids (GCs) in RA.MethodsA protocolised systematic review and meta-analysis (PROSPERO No. CRD42021252528) of double-blind, placebo-controlled randomised trials (RCTs) comparing a low dose of GCs (≤ 7.5mg/day prednisone) to placebo over at least 2 years was performed. The primary outcome investigated was adverse events (AEs). We performed random-effects meta-analyses and used the Cochrane RoB tool and GRADE to assess risk of bias and quality of evidence (QoE).ResultsSix trials with 1078 participants were included. There was no evidence of an increased risk of AEs (incidence rate ratio 1.08; 95% CI 0.86, 1.34; P = 0.52); however, the QoE was low. The risks of death, serious AEs, withdrawals due to AEs, and AEs of special interest did not differ from placebo (very low to moderate QoE). Infections occurred more frequently with GCs (risk ratio 1.4; 1.19–1.65; moderate QoE). Concerning benefit, we found moderate to high quality evidence of improvement in disease activity (DAS28: −0.23; −0.43 to −0.03), function (HAQ −0.09; −0.18 to 0.00), and Larsen scores (–4.61; −7.52 to −1.69). In other efficacy outcomes, including Sharp van der Heijde scores, there was no evidence of benefits with GCs.ConclusionThere is very low to moderate QoE for no harm with long-term low dose GCs in RA, except for an increased risk of infections in GC users. The benefit-risk ratio might be reasonable forusing low-dose long-term GCs considering the moderate to high quality evidence for disease-modifying properties.

ObjectivesSelf-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.MethodsA 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.ResultsThere 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.ConclusionAlthough 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.

Objective To determine the effect of a multidisciplinary lifestyle program in patients with RA with low–moderate disease activity. Methods In the ‘Plants for Joints’ (PFJ) parallel-arm, assessor-blind randomized controlled trial, patients with RA and 28-joint DAS (DAS28) ≥2.6 and ≤5.1 were randomized to the PFJ or control group. The PFJ group followed a 16-week lifestyle program based on a whole-food plant-based diet, physical activity and stress management. The control group received usual care. Medication was kept stable 3 months before and during the trial whenever possible. We hypothesized that PFJ would lower disease activity (DAS28). Secondary outcomes included anthropometric, metabolic and patient-reported measures. An intention-to-treat analysis with a linear mixed model adjusted for baseline values was used to analyse between-group differences. Results Of the 83 people randomized, 77 completed the study. Participants were 92% female with mean (s.d.) age of 55 (12) years, BMI of 26 (4) kg/m2 and mean DAS28 of 3.8 (0.7). After 16 weeks the PFJ group had a mean 0.9-point greater improvement of DAS28 vs the control group (95% CI 0.4, 1.3; P Conclusion The 16-week PFJ multidisciplinary lifestyle program substantially decreased disease activity and improved metabolic status in people with RA with low–moderate disease activity. Trial Registration International Clinical Trials Registry Platform; https://www.who.int/clinical-trials-registry-platform; NL7800.

INTRODUCTION: OMERACT uses an evidence-based framework known as the 'OMERACT Filter Instrument Selection Algorithm' (OFISA) to guide decisions in the assessment of outcome measurement instruments for inclusion in a core outcome set for interventional and observational clinical trials.METHODS: A group of OMERACT imaging and patient-centered outcome methodologists worked with imaging outcome groups to facilitate the selection of imaging outcome measurement instruments using the OFISA approach. The lessons learned from this work influenced the evolution to Filter 2.2 and necessitated changes to OMERACT's documentation and processes.RESULTS: OMERACT has revised documentation and processes to incorporate the evolution of instrument selection to Filter 2.2. These revisions include creation of a template for detailed definitions of the target domain which is a necessary first step for instrument selection, modifications to the Summary of Measurement Properties (SOMP) table to account for sources of variability, and development of standardized reporting tables for each measurement property.CONCLUSIONS: OMERACT Filter 2.2 represents additional modifications of the OMERACT guide for working groups in their rigorous assessment of measurement properties of instruments of various types, including imaging outcome measurement instruments. Enhanced reporting aims to increase the transparency of the evidence base leading to judgements for the endorsement of instruments in core outcome sets.

Background: Data are scarce on immunogenicity of COVID-19 vaccines in patients with autoimmune diseases, who are often treated with immunosuppressive drugs. We aimed to investigate the effect of different immunosuppressive drugs on antibody development after COVID-19 vaccination in patients with autoimmune diseases. Methods: In this study, we used serum samples collected from patients with autoimmune diseases and healthy controls who were included in two ongoing prospective cohort studies in the Netherlands. Participants were eligible for inclusion in this substudy if they had been vaccinated with any COVID-19 vaccine via the Dutch national vaccine programme, which at the time was prioritising vaccination of older individuals. Samples were collected after the first or second COVID-19 vaccination. No serial samples were collected. Seroconversion rates and IgG antibody titres against the receptor-binding domain of the SARS-CoV-2 spike protein were measured. Logistic and linear regression analyses were used to investigate the association between medication use at the time of vaccination and at least until sampling, seroconversion rates, and IgG antibody titres. The studies from which data were collected are registered on the Netherlands Trial Register, Trial ID NL8513, and ClinicalTrials.org, NCT04498286.Findings: Between April 26, 2020, and March 1, 2021, 3682 patients with rheumatic diseases, 546 patients with multiple sclerosis, and 1147 healthy controls were recruited to participate in the two prospective cohort studies. Samples were collected from patients with autoimmune diseases (n=632) and healthy controls (n=289) after their first (507 patients and 239 controls) or second (125 patients and 50 controls) COVID-19 vaccination. The mean age of both patients and controls was 63 years (SD 11), and 423 (67%) of 632 patients with autoimmune diseases and 195 (67%) of 289 controls were female. Among participants without previous SARS-CoV-2 infection, seroconversion after first vaccination were significantly lower in patients than in controls (210 [49%] of 432 patients vs 154 [73%] of 210 controls; adjusted odds ratio 0·33 [95% CI 0·23-0·48]; pInterpretation: Our data suggest that seroconversion after a first COVID-19 vaccination is delayed in older patients on specific immunosuppressive drugs, but that second or repeated exposure to SARS-CoV-2, either via infection or vaccination, improves humoral immunity in patients treated with immunosuppressive drugs. Therefore, delayed second dosing of COVID-19 vaccines should be avoided in patients receiving immunosuppressive drugs. Future studies that include younger patients need to be done to confirm the generalisability of our results.FUNDING: ZonMw, Reade Foundation, and MS Center Amsterdam.

Objective Our primary objective was to develop an Outcome Measures in Rheumatology (OMERACT) core domain set to capture the impact of glucocorticoids (GC), both positive and negative, on patients with Rheumatic conditions. Methods The OMERACT Filter 2.1 was used to guide core domain selection. Systematic literature reviews, qualitative studies and quantitative surveys were conducted by the OMERACT GC Impact working group to identify candidate domains for a core domain set. A summary of prior work and Delphi exercise were presented at the OMERACT 2020 virtual GC workshop. A proposed GC Impact core domain set derived from this work was presented for discussion in facilitated breakout groups. Participants voted on the proposed GC Impact core domain set. Results 113 people, including 23 patient research partners, participated in two virtual workshops conducted at different times on the same day. The proposed mandatory domains to be evaluated in clinical trials involving GCs were: infection, bone fragility, hypertension, diabetes, weight, fatigue, mood disturbance and death. In addition, collection of disease specific outcomes was included in the core domain set as “mandatory in specific circumstances”. The proposed core domain set was endorsed by 100% (23/23) of the patient research partners and 92% (83/90) of the remaining participants, including clinicians, researchers and industry stakeholders. Conclusion A GC Impact core domain set was endorsed at the OMERACT 2020 virtual workshop. The OMERACT GC Impact working group will now progress to identify, develop and validate measurement tools to best address these domains in clinical trials.

Objectives Imaging is one of the most rapidly evolving fields in medicine. Unfortunately, many imaging technologies have been applied as measurement instruments without rigorous evaluation of the evidence supporting their truth, discriminatory capability and feasibility for that context of use. The Outcome Measures in Rheumatology (OMERACT) Filter 2.1 Instrument Selection Algorithm (OFISA) is used to evaluate such evidence for use of an instrument in a research setting. The objectives of this work are to: [1] define and describe the key conceptual aspects that are essential for the evaluation of imaging as an outcome measurement instrument and [2] describe how these aspects can be assessed through OFISA. Methods Experts in imaging and/or methodology met to formalize concepts and define key steps. These concepts were discussed with a team of patient research partners with interest in imaging to refine technical and methodological aspects into comprehensible information. A workshop was held at OMERACT2020 and feedback was incorporated into existing OMERACT process for domain and instrument selection. Results Three key lessons were identified: (1) a clear definition of the domain we want to measure is a necessary prerequisite to the selection of a good instrument, (2) the sources of variability that can directly influence the instrument should be clearly identified, (3) incorporating these first two lessons into OFISA improves the quality of every instrument selection process. Conclusions The incorporation of these lessons in the updated OMERACT Filter (now 2.2) will improve the quality of the selection process for all types of outcome measurement instruments.

Objectives To identify highly ranked features related to clinicians’ diagnosis of clinically relevant knee OA. Methods General practitioners (GPs) and secondary care physicians (SPs) were recruited to evaluate 5–10 years follow-up clinical and radiographic data of knees from the CHECK cohort for the presence of clinically relevant OA. GPs and SPs were gathered in pairs; each pair consisted of one GP and one SP, and the paired clinicians independently evaluated the same subset of knees. A diagnosis was made for each knee by the GP and SP before and after viewing radiographic data. Nested 5-fold cross-validation enhanced random forest models were built to identify the top 10 features related to the diagnosis. Results Seventeen clinician pairs evaluated 1106 knees with 139 clinical and 36 radiographic features. GPs diagnosed clinically relevant OA in 42% and 43% knees, before and after viewing radiographic data, respectively. SPs diagnosed in 43% and 51% knees, respectively. Models containing top 10 features had good performance for explaining clinicians’ diagnosis with area under the curve ranging from 0.76–0.83. Before viewing radiographic data, quantitative symptomatic features (i.e. WOMAC scores) were the most important ones related to the diagnosis of both GPs and SPs; after viewing radiographic data, radiographic features appeared in the top lists for both, but seemed to be more important for SPs than GPs. Conclusions Random forest models presented good performance in explaining clinicians’ diagnosis, which helped to reveal typical features of patients recognized as clinically relevant knee OA by clinicians from two different care settings.

Objective To develop prediction models for individual patient harm and benefit outcomes in elderly patients with RA and comorbidities treated with chronic low-dose glucocorticoid therapy or placebo. Methods In the Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) study, 451 RA patients ≥65 years of age were randomized to 2 years 5 mg/day prednisolone or placebo. Eight prediction models were developed from the dataset in a stepwise procedure based on prior knowledge. The first set of four models disregarded study treatment and examined general predictive factors. The second set of four models was similar but examined the additional role of low-dose prednisolone. In each set, two models focused on harm [the occurrence of one or more adverse events of special interest (AESIs) and the number of AESIs per year) and two on benefit (early clinical response/disease activity and a lack of joint damage progression). Linear and logistic multivariable regression methods with backward selection were used to develop the models. The final models were assessed and internally validated with bootstrapping techniques. Results A few variables were slightly predictive for one of the outcomes in the models, but none were of immediate clinical value. The quality of the prediction models was sufficient and the performance was low to moderate (explained variance 12–15%, area under the curve 0.67–0.69). Conclusion Baseline factors are not helpful in selecting elderly RA patients for treatment with low-dose prednisolone given their low power to predict the chance of benefit or harm. Trial registration https://clinicaltrials.gov; NCT02585258.

Objective.To reduce the diagnostic delay in axial spondyloarthritis (axSpA), guidelines recommend referring patients with acute anterior uveitis (AAU) and chronic back pain (CBP) to a rheumatologist. This observational study in daily practice evaluated the prevalence of previously unrecognized axSpA in patients with AAU who were referred by ophthalmologists because of concurrent CBP.Methods.All patients with AAU referred with CBP (≥ 3 months, age of onset < 45 yrs) from 5 ophthalmology clinics underwent rheumatologic assessment, including pelvic radiographs. Patients with previously diagnosed rheumatic disease and AAU due to other causes were excluded. The primary endpoint was a clinical axSpA diagnosis by the rheumatologist.Results.Eighty-one patients fulfilled the referral criteria (52% male, 56% HLA-B27 positive, median age 41 yrs, median CBP duration 10 yrs). In total, 58% (n = 47) had recurring AAU, of whom 87% already had CBP during previous AAU attacks. After assessment, 23% (n = 19) of patients were clinically diagnosed with definite axSpA (10/19 radiographic), 40% (n = 32) with suspicion of axSpA, and 37% (n = 30) with no axSpA. AxSpA was diagnosed more often in men (33% of the men vs 13% of the women).Conclusion.A high prevalence of axSpA was found in patients with AAU referred because of CBP. There was substantial diagnostic delay in the majority of patients with recurring AAU, as many already had CBP during previous AAU flares. In AAU, screening for CBP and prompt referral has a high diagnostic yield and should consistently be promoted among ophthalmologists.

Background To add context to the impact of medical conditions, it is important to interpret and compare health outcomes across studies and populations. We aimed to determine Dutch reference values for the Patient-Reported Outcomes Measurement Information System Scale v1.2 - Global Health (PROMIS-GH). Methods The PROMIS-GH, also referred to as PROMIS-10, was completed by 4370 Dutch persons, representative for the 2016 Dutch population. T-scores for the mental health (GMH) and physical health (GPH) subscales, and their shorter two-item subscales, were calculated for the entire population, age groups and gender. T-scores for GMH and GPH were compared to the US reference population, representative for the 2000 US general population. Interpretability thresholds for poor, fair, good, very good and excellent GPH and GMH were calculated based on T-scores of participants, which were categorized into five groups based on their response to item Global01. For each group the mean GPH and GMH T-score was calculated and the midpoint between two adjacent means was identified, resulting in thresholds. Thresholds based on the Dutch data were compared to US thresholds. Results The Dutch population had a GMH T-score of 44.7 and a GPH T-score of 45.2, both substantially worse than the US reference population T-score of 50. Lower T-scores were also found for age-range and gender subpopulations. Dutch GMH and GPH interpretability thresholds were mostly not substantially different compared to the US thresholds, although the Dutch threshold between fair and poor mental health was considerably higher (29 vs. 38). Conclusions This study reports reference values for the PROMIS-GH scale for the Dutch general population, including age-range and gender subpopulations. These reference values provide an important tool for healthcare professionals and researchers to better evaluate and interpret patient-reported mental health and physical health. Scores are notably worse than the US reference values. The exact reason for this remains subject for further research, although possibilities for the differences are discussed, including the presence of differential item functioning and the representativeness and recentness of the data.

Summary Background The Harmonising Outcome Measures for Eczema (HOME) initiative has established a core outcome set of domains for atopic eczema (AE) clinical trials. Previous consensus meetings have agreed on preferred instruments for clinician‐reported signs (Eczema Area and Severity Index, EASI) and patient‐reported symptoms (Patient‐Oriented Eczema Measure, POEM). This paper reports consensus decisions from the HOME VII meeting. Objectives To complete the core outcome set for AE by agreeing on core outcome instruments for the domains of quality of life (QoL), long‐term control and itch intensity. Methods A face‐to‐face consensus meeting was held in Tokyo, Japan (8–10 April 2019) including 75 participants (49 healthcare professionals/methodologists, 14 patients, 12 industry representatives) from 16 countries. Consensus decisions were made by presentations of evidence, followed by whole and small group discussions and anonymous voting using predefined consensus rules. Results It was agreed by consensus that QoL should be measured using the Dermatology Life Quality Index (DLQI) for adults, the Children’s Dermatology Life Quality Index (CDLQI) for children and the Infant’s Dermatology Quality of Life Index (IDQoL) for infants. For long‐term control, the Recap of Atopic Eczema (RECAP) instrument or the Atopic Dermatitis Control Test (ADCT) should be used. Consensus was not reached over the frequency of data collection for long‐term control. The peak itch numerical rating scale (NRS)‐11 past 24 h was recommended as an additional instrument for the symptom domain in trials of older children and adults. Agreement was reached that all core outcome instruments should be captured at baseline and at the time of primary outcome assessment as a minimum. Conclusions For now, the core outcome set for clinical trials in AE is complete. The specified domains and instruments should be used in all new clinical trials and systematic reviews of eczema treatments., What is already known about this topic? Core outcomes sets improve the design and reporting of clinical trials, reduce selective outcome reporting bias and facilitate meta‐analysis of results in systematic reviews.The HOME core outcome set for eczema recommends the inclusion of four core domains in all atopic eczema trials: clinician‐reported signs, patient‐reported symptoms, health‐related quality of life (HrQoL) and long‐term control.Clinician‐reported signs should be captured using the Eczema Area and Severity Index (EASI) and patient‐reported symptoms using the Patient‐Oriented Eczema Measure (POEM). What does this study add? The HOME core outcome set is now complete and recommended core outcome instruments have been agreed on for all four domains.Core outcome instruments for HrQoL: Dermatology Life Quality Index (DLQI) for adults, Children’s Dermatology Life Quality Index (CDLQI) for children and Infant’s Dermatology Quality of Life Index (IDQoL) for infants.Core outcome instruments for long‐term control: either the Recap of Atopic Eczema (RECAP) or the Atopic Dermatitis Control Test (ADCT).In addition, itch intensity should be measured using the peak NRS‐11 past 24 h for trials including older children and adults. What are the clinical implications of this work? If all future trials of eczema treatments include the HOME core outcome instruments, then trial results will be more readily incorporated into meta‐analyses in systematic reviews and clinical care will be informed by the best available evidence. Linked Comment: D.F. Murrell and C.F. Paul. Br J Dermatol 2021; 185:13–14.

Contains fulltext : 251785.pdf (Publisher’s version ) (Closed access)

Background/Aims Power Doppler ultrasound (PDUS) is a sensitive non-invasive imaging tool to visualize a wide range of articular and periarticular inflammation in psoriatic arthritis (PsA). ULTIMATE (NCT02662985) is the first large RCT that used ultrasound with Global OMERACT ultrasound synovitis score (GLOESS) as the primary endpoint, to demonstrate early benefits of secukinumab on synovitis in patients with PsA through 12 weeks. Here we report the responsiveness of ultrasound on synovitis and enthesitis, clinical efficacy, and safety of secukinumab up to 52 weeks. Methods This was a 52-week study with 12-week double-blind placebo-controlled treatment followed by 12-week open-label treatment and 6-month open-label extension treatment in all patients. Synovitis and ultrasound enthesitis response were measured by GLOESS and Global OMERACT enthesitis score (definitions 1 and 2) at patient level, respectively. Other assessments across key PsA manifestations of joints (ACR responses), enthesitis, (SPARCC), skin (PASI responses), dactylitis (LDI) and physical function (HAQ-DI) were also evaluated. Data are presented as observed. Results A total of 166 patients were enrolled, of which 90% (75/83) of secukinumab and 83% (69/83) of placebo-secukinumab participants completed 52 weeks. A continued improvement in GLOESS was observed in both secukinumab and placebo-secukinumab groups after switching to active therapy at Week 12 through Week 52 and a similar trend of improvement in Global OMERACT enthesitis score (definition 1 and 2) was observed up to 52 weeks in both groups (Table). At 52 weeks, sustained clinical response rates were observed in secukinumab (ACR20, 89%; ACR50, 68%; ACR70, 48%; PASI 90, 59%; PASI 100, 55%) and placebo-secukinumab groups (ACR20, 84%; ACR50, 72%; ACR70, 47%; PASI 90, 74%; PASI 100, 48%). Mean changes from baseline at Week 52 in HAQ-DI and SPARCC were -3.0 and -0.8 and -3.6 and -0.7 for secukinumab and placebo-secukinumab, respectively. There were no new or unexpected safety findings. Conclusion ULTIMATE demonstrated the responsiveness of ultrasound on both synovitis and enthesitis outcomes in PsA supporting its use in clinical trials, and confirmed the rapid and continued benefits of secukinumab through 52 weeks. Sustained efficacy was also observed across key clinical PsA manifestations with a safety profile consistent with previous reports. Disclosure P.G. Conaghan: Consultancies; AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer. Member of speakers’ bureau; AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer. M.A. D’Agostino: Consultancies; Sanofi, Novartis, BMS, Janssen, Celgene, Roche, AbbVie, UCB, Eli Lilly. Member of speakers’ bureau; Sanofi, Novartis, BMS, Janssen, Celgene, Roche, AbbVie, UCB, Eli Lilly. G. Schett: Member of speakers’ bureau; AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche, UCB. C. Guerrero: None. P. Hanova: None. T. Cazenave: None. M.S. Stoenoiu: Honoraria; Roche, AbbVie, BMS, Gilead, Jonsson, MSD, Novartis, Pfizer, UCB. Member of speakers’ bureau; Roche, AbbVie, UCB. Grants/research support; Roche, AbbVie, UCB. M. Backhaus: Honoraria; Roche, AbbVie, BMS, Gilead, Jonsson, MSD, Novartis, Pfizer, UCB. Member of speakers’ bureau; Roche, AbbVie, UCB. Grants/research support; Roche, AbbVie, UCB. G. Mouterde: Consultancies; AbbVie, Lilly. Honoraria; AbbVie, BMS, Lilly, Novartis, Pfizer, Roche, Chugai, UCB. Grants/research support; Celgene, Pfizer. M. Boers: Consultancies; BMS, Novartis, Pfizer, GSK. A. Duggan: Other; Employee of Novartis. P. Goyanka: Other; Employee of Novartis MSD. C. Gaillez: Shareholder/stock ownership; Novartis, BMS. Other; Employee of Novartis.

Objective: Pain interference and pain behavior are highly relevant outcomes in patients with rheumatoid arthritis (RA). The Patient-Reported Outcomes Measurement Information System (PROMIS) is a universally applicable set of item banks measuring patient-reported health, and if applied as computerized adaptive tests (CATs), more efficiently and precisely than current instruments. The objective was to study the psychometric properties of the Dutch-Flemish PROMIS pain interference (PROMIS-PI) and the PROMIS pain behavior (PROMIS-PB) item banks in patients with RA. Methods: A total of 2,029 patients with RA completed the full PROMIS-PI (version 1.1, 40 items), and 1,554 patients completed the full PROMIS-PB (version 1.1, 39 items). The following psychometric properties were studied: unidimensionality, local dependence, monotonicity and graded response model (GRM) fit, cross-cultural validity (differential item functioning [DIF] for language [Dutch versus Flemish]), other forms of measurement invariance, construct validity, reliability, and floor and ceiling effects. Results: The PROMIS-PI and PROMIS-PB banks were sufficiently unidimensional (Omega-hierarchical [Omega-H] 0.99, 0.95, and explained common variance 0.95, 0.78, respectively), had negligible local dependence (0.3–1.4% of item pairs), good monotonicity (H 0.75, 0.46), and a good GRM model fit (no misfitting items). Furthermore, both item banks showed good cross-cultural validity (no DIF for language), measurement invariance (no DIF for age, sex, administration mode, and disease activity), good construct validity (all hypotheses met), high reliability (>0.90 in the range of patients with RA), and an absence of floor and ceiling effects (0% minimum or maximum score, respectively). Conclusion: Both PROMIS-PI and PROMIS-PB banks showed good psychometric properties in patients with RA and can be used as CATs in research and clinical practice.