Stakeholder endorsement advancing the implementation of a patient-reported domain for harms in rheumatology clinical trials: Outcome of the OMERACT Safety Working Group.

OBJECTIVES: To develop an understanding of the concept of safety/harms experienced by patients involved in clinical trials for their rheumatic and musculoskeletal diseases (RMDs) and to seek input from the OMERACT community before moving forward to developing or selecting an outcome measurement instrument. METHODS: OMERACT 2023 presented and discussed interview results from 34 patients indicating that up to 171 items might be important for patients' harm-reporting. RESULTS: Domain was defined in detail and supported by qualitative work. Participants in the Special-Interest-Group endorsed (96 %) that enough qualitative data are available to start Delphi survey(s). CONCLUSION: We present a definition of safety/harms that represents the patient voice (i.e., patients' perception of safety) evaluating the symptomatic treatment-related adverse events for people with RMDs enrolled in clinical trials.

Optimizing Reliability of Real-Time Sonographic Examination and Scoring of Joint Synovitis in Rheumatoid Arthritis.

OBJECTIVE: Musculoskeletal ultrasound real-time image acquisition and scoring are complex, and many factors affect reliability. Static image reliability does not guarantee real-time scoring. This study aimed to identify factors and solutions to improve real-time scoring reliability for the grey scale and power Doppler evaluation of synovitis. We also report on using a novel musculoskeletal ultrasound synovitis rule-based scoring atlas. METHODS: In four stages, we evaluated inter- and intra-reader reliability among three ultrasonographers (US1-3). Intra- and inter-reader reliability was calculated using weighted-kappa, intraclass correlation coefficient, and Spearman correlation. Reliability statistics were compared between stages using permutation tests to compute empirical distributions for differences in those statistics. At each stage, factors that diminished reliability were identified and addressed. After intensive reliability exercises, a RA MSUS atlas with in-depth scoring rules was generated to improve interpretive reliability. RESULTS: The three ultrasonographers had good to excellent intra-reader reliability for real-time acquisition scoring over 2432 views (weighted kappa 0.52-0.80, intraclass correlation coefficient 0.59-0.86, and Spearman correlation 0.64-0.86). Inter-reader reliability was good to excellent between US1/US2 and US1/US3 (weighted kappa 0.51-0.66, intraclass correlation coefficient 0.66-0.75, Spearman correlation 0.59-0.73). US1 achieved significant improvement in intra-reader reliability from stage 1 to stage 2 (p<0.05, weighted-kappa 0.63 to 0.80, intraclass correlation coefficient 0.71 to 0.86, Spearman 0.67 to 0.86) with use of the atlas.  Conclusion: This rheumatoid arthritis musculoskeletal ultrasound study addressed complex factors affecting musculoskeletal ultrasound acquisition-scoring reliability. Systematic identification and amelioration of many factors and using a novel rule-based scoring atlas significantly improved intra-reader reliability.

OMERACT consensus-based operational definition of contextual factors in rheumatology clinical trials: A mixed methods study.

OBJECTIVES: To develop an operational definition of contextual factors (CF) [1]. METHODS: Based on previously conducted interviews, we presented three CF types in a Delphi survey; Effect Modifying -, Outcome Influencing - and Measurement Affecting CFs. Subsequently, a virtual Special Interest Group (SIG) session was held for in depth discussion of Effect Modifying CFs. RESULTS: Of 161 Delphi participants, 129 (80%) completed both rounds. After two rounds, we reached consensus (≥70% agreeing) for all but two statements. The 45 SIG participants were broadly supportive. CONCLUSION: Through consensus we developed an operational definition of CFs, which was well received by OMERACT members.

Harms reported by patients in rheumatology drug trials: a systematic review of randomized trials in the cochrane library from an OMERACT working group.

BACKGROUND: Underreporting of harms in randomized controlled trials (RCTs) may lead to incomplete or erroneous assessments of the perceived benefit-to-harm profile of an intervention. To compare benefit with harm in clinical practice and future clinical studies, adverse event (AE) profiles including severity need to be understood. Even though patients report harm symptoms earlier and more frequently than clinicians, rheumatology RCTs currently do not provide a reporting framework from the patient's perspective regarding harms. Our objective for this meta-research project was to identify AEs in order to determine harm clusters and whether these could be self-reported by patients. Our other objective was to examine reported severity grading of the reported harms. METHODS: We considered primary publications of RCTs eligible if they were published between 2008 and 2018 evaluating pharmacological interventions in patients with a rheumatic or musculoskeletal condition and if they were included in Cochrane reviews. We extracted data on harms such as reported AE terms together with severity (if described), and categorized AE- and severity-terms into overall groups. We deemed all AEs with felt components appropriate for patient self-reporting. RESULTS: The literature search identified 187 possible Cochrane reviews, of which 94 were eligible for evaluation, comprising 1,297 articles on individual RCTs. Of these RCTs, 93 pharmacological trials met our inclusion criteria (including 31,023 patients; representing 20,844 accumulated patient years), which reported a total of 21,498 AEs, corresponding to 693 unique reported terms for AEs. We further sub-categorized these terms into 280 harm clusters (i.e., themes). AEs appropriate for patient self-reporting accounted for 58% of the AEs reported. Among the reported AEs, we identified medical terms for all of the 117 harm clusters appropriate for patient reporting and lay language terms for 86%. We intended to include severity grades of the reported AEs, but there was no evidence for systematic reporting of clinician- or patient-reported severity in the primary articles of the 93 trials. However, we identified 33 terms suggesting severity, but severity grading was discernible in only 9%, precluding a breakdown by severity in this systematic review. CONCLUSIONS: Our results support the need for a standardized framework for patients' reporting of harms in rheumatology trials. Reporting of AEs with severity should be included in future reporting of harms, both from the patients' and investigators' perspectives. REGISTRATION: PROSPERO: CRD42018108393.

Towards consensus in defining and handling contextual factors within rheumatology trials: an initial qualitative study from an OMERACT working group.

OBJECTIVES: The Outcome Measures in Rheumatology Initiative established the Contextual Factors Working Group to guide the understanding, identification and handling of contextual factors for clinical trials. In clinical research, different uses of the term 'contextual factors' exist. This study explores the perspectives of researchers (including clinicians) and patients in defining 'contextual factor' and its related terminology, identifying such factors and accounting for them in trials across rheumatology. METHODS: We conducted individual semistructured interviews with researchers (including clinicians) who have experience within the field of contextual factors in clinical trials or other potentially relevant areas, and small focus group interviews with patients with rheumatic conditions. We transcribed the interviews and applied qualitative content analysis. RESULTS: We interviewed 12 researchers and 7 patients. Researcher's and patient's descriptions of contextual factors were categorised into two broad themes, each comprising two contextual factors types. The 'treatment effect' theme focused on factors explaining variations in treatment effects (A) among patients and (B) among studies. The 'outcome measurement' theme focused on factors that explain (C) variations in the measurement result itself (apart from actual changes/differences in the outcome) and (D) variations in the outcome itself (beside treatment of interest). Methods for identifying and handling contextual factors differed among these themes and types. CONCLUSIONS: Two main themes for contextual factors with four types of contextual factors were identified based on input from researchers and patients. This will guide operationalisation of contextual factors. Further research should refine our findings and establish consensus among relevant stakeholders.

Population characteristics as important contextual factors in rheumatological trials: an exploratory meta-epidemiological study from an OMERACT Working Group.

OBJECTIVES: To explore whether trial population characteristics modify treatment responses across various interventions, comparators and rheumatic conditions. METHODS: In this meta-epidemiological study, we included trials from systematic reviews available from the Cochrane Musculoskeletal Group published up to 23 April 2019 in Cochrane Library with meta-analyses of five or more randomised controlled trials (RCTs) published from year 2000. From trial reports, we extracted data on 20 population characteristics. For characteristics with sufficient data (ie, available for ≥2/3 of the trials), we performed multilevel meta-epidemiological analyses. RESULTS: We identified 19 eligible systematic reviews contributing 187 RCTs (212 comparisons). Only age and sex were explicitly reported in ≥2/3 of the trials. Using information about the country of the trials led to sufficient data for five further characteristics, that is, 7 out of 20 (35%) protocolised characteristics were analysed. The meta-regressions showed effect modification by economic status, place of residence, and, nearly, from healthcare system (explaining 4.8%, 0.9% and 1.5% of the between-trial variation, respectively). No effect modification was demonstrated from age, sex, patient education/health literacy or predominant religion. CONCLUSIONS: This study demonstrates the scarce reporting of most population characteristics, hampering investigation of their impact with meta-research. Our sparse results suggest that place of residence (ie, continent of the trial), economic status (based on World Bank classifications) and healthcare system (based on WHO index for health system performance) may be important in explaining the variation in treatment response across trials. There is an urgent need for consistent reporting of important population characteristics in trials. PROSPERO REGISTRATION NUMBER: CRD42019127642.

Rheumatology Common Toxicity Criteria (RCTC): An Update Reflecting Real-World Use.

INTRODUCTION: The Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatology Common Toxicity Criteria (RCTC) version 2.0 was published in 2007 by the OMERACT Drug Safety Working Group, building on limited experience with RCTC version 1.0, to facilitate standardization of assessment (grading) and reporting of adverse events (AEs) commonly seen in rheumatic disease clinical trials (Woodworth et al. in J Rheumatol 34:1401-1414, 2007). OBJECTIVES: The objectives of this study were to (1) report the real-world performance of RCTC 2.0; (2) report immediately correctable errors in RCTC 2.0, and provide a revised RCTC 2.1; and (3) begin to identify the need for a comprehensive revision of RCTC 2.0. METHODS: Safety data outputs for several large rheumatic/autoimmune disease clinical trials in which RCTC 2.0 was used were evaluated for accuracy of reporting and the ability to assess differences among treatments. We examined RCTC 2.0 tables for errors, as well as for omission of terms for AEs that commonly occur in more recent rheumatology clinical trials. We also considered recommendations from recent US Food and Drug Administration (FDA) and international initiatives such CDISC (Clinical Data Interchange Standards Consortium) to improve the consistency of safety data collection and interpretability of safety data analyses. RESULTS: RCTC 2.0 enabled comparisons of safety data across treatment groups, including grading. However, we discovered inaccuracies in laboratory results grading and omission of AE terms now recognized to occur in rheumatic disease clinical trials. CONCLUSION: The RCTC 2.0 performed as intended, although some inaccuracies and omissions were found. We provide a corrected version, RCTC 2.1, and also recommend further revision of the RCTC within OMERACT guidances to include AEs that have been reported in rheumatology clinical trials since RCTC 2.0 was published. Ideally, a revised RCTC 3.0 would not only facilitate standardized assessment and reporting of AEs, but would also expand and encourage accurate comparison of the safety profiles of treatments for rheumatic/autoimmune diseases.

Identifying Possible Outcome Domains from Existing Outcome Measures to Inform an OMERACT Core Domain Set for Safety in Rheumatology Trials.

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Safety Working Group objective was to identify harm domains from existing outcome measurements in rheumatology. METHODS: Systematically searching the MEDLINE database on January 24, 2017, we identified full-text articles that could be used for harm outcomes in rheumatology. Domains/items from the identified instruments were described and the content synthesized to provide a preliminary framework for harm outcomes. RESULTS: From 435 possible references, 24 were read in full text and 9 were included: 7 measurement instruments were identified. Investigation of domains/items revealed considerable heterogeneity in the grouping and approach. CONCLUSION: The ideal way to assess harm aspects from the patients' perspective has not yet been ascertained.

Identifying Provisional Generic Contextual Factor Domains for Clinical Trials in Rheumatology: Results from an OMERACT Initiative.

OBJECTIVE: The Contextual Factors Working Group aims to provide guidance on addressing contextual factors in rheumatology trials within OMERACT. METHODS: During the Special Interest Group session at OMERACT 2018, preliminary results were presented from a case scenario survey and semistructured interviews, including contextual factors mentioned in these. A group-based exercise sought to identify and rank important generic contextual factors. RESULTS: A total of 79 candidate factors were listed. Across the 3 groups, gender/sex, comorbidities, and the healthcare system were ranked as most important. CONCLUSION: The identified important contextual factor domains may be considered a provisional list pending further research.

Obesity Impacts Swelling of Ankle and Foot Joints in Early Rheumatoid Arthritis Patients.

OBJECTIVE: The evaluation of disease activity in obese rheumatoid arthritis (RA) patients presents challenges particularly in the clinical assessment of swollen joints. This study examines the effect of obesity on the American College of Rheumatology (ACR) core set measures used in assessing RA disease activity with specific focus on the swollen joint count (SJC). METHODS: We examined a cross-sectional cohort of 323 early seropositive RA patients (symptom duration ≤15 months). Patients were biologic-naive with equal to or more than 6/44 SJC and equal to or more than 9/44 tender joint count. The ACR core set measures, components of Disease Activity Score (DAS) 44/erythrocyte sedimentation rate (ESR), DAS28/ESR4 item, Clinical Disease Activity Index (CDAI), and body mass index (BMI) were collected. Disease activity measures were compared between BMI categories. Multivariable linear regression models assessed the relationship between high BMI (≥30 kg/m) and lower-extremity (LE) SJC and SJC44 while accounting for other ACR measures. RESULTS: Disease Activity Score 44/ESR4 item, Health Assessment Questionnaire Disability Index, physician global, and SJC44 differed across BMI categories (p < 0.05). Of the SJC44, metacarpophalangeal joints and LE joints (knees, ankles, metatarsophalangeal joints) were associated with increased swelling in all BMI groups (P < 0.05). Obesity was significantly associated with LE SJC after adjusting for ACR core set measures. CONCLUSIONS: There is a direct association between increased BMI and increased swelling of LE joints in RA patients. Increases in DAS44-measured disease activity are higher in obese RA patients because of increased LE swollen joints. Disease Activity Score 28 and Clinical Disease Activity Index, which emphasize upper-extremity joint assessment, are not significantly influenced by obesity.

Ultra-low doses of rituximab for continued treatment of rheumatoid arthritis (REDO study): a randomised controlled non-inferiority trial.

BACKGROUND: Rituximab is an effective treatment for rheumatoid arthritis, given as either two doses of 1000 mg (2 weeks apart) every 6 months (the dose recommended by the US Food and Drug Administration and European Medicines Agency) or two doses of 500 mg (2 weeks apart) or one dose of 1000 mg (a standard low dose) every 6 months. Findings of several small uncontrolled studies suggest that doses lower than the recommended dose or standard low dose might be sufficient for maintenance treatment, potentially improving safety and reducing costs. Therefore, we aimed to compare the efficacy of ultra-low doses of rituximab (one dose of 500 mg or 200 mg) with a standard low dose of rituximab (one dose of 1000 mg) for patients with rheumatoid arthritis who respond to standard doses of rituximab. METHODS: The REDO study is a randomised, double-blind, non-inferiority trial done at five centres in the Netherlands. Adults (aged ≥18 years) with rheumatoid arthritis responding well to rituximab were randomly allocated (1:2:2) to receive intravenous rituximab as one dose of either 1000 mg, 500 mg, or 200 mg, respectively. Volumes of all doses were equal to achieve masking. Randomisation lists were computer-generated and stratified by rheumatoid factor or anti-citrullinated protein antibody status (positive or negative) and concomitant use of conventional synthetic disease modifying antirheumatic drugs (yes or no). The primary analysis was a per-protocol hierarchical testing procedure comparing ultra-low doses with a standard low dose (500 mg vs 1000 mg at 3 months, followed by 500 mg vs 1000 mg at 6 months, 200 mg vs 1000 mg at 3 months, and 200 mg vs 1000 mg at 6 months), using a non-inferiority margin of 0·60 on change from baseline in the 28-joint disease activity score based on C-reactive protein levels (DAS28-CRP). The study is registered at www.trialregister.nl, NTR6117. FINDINGS: Between Dec 15, 2016, and Sept 20, 2018, 142 patients were randomly allocated to either 1000 mg rituximab (n=29), 500 mg rituximab (n=58), or 200 mg rituximab (n=55). The 500 mg dose was non-inferior to 1000 mg at 3 months (mean change from baseline in DAS28-CRP, -0·07, 95% CI -0·41 to 0·27) but not at 6 months (0·29, -0·08 to 0·65). Because of the hierarchical testing procedure, non-inferiority could not be tested for the 200 mg dose. 13 patients had serious adverse events, three (10%) in the 1000 mg group, six (10%) in the 500 mg group, and four (7%) in the 200 mg group. The most frequently reported serious adverse events were cardiovascular. No deaths occurred during the study. A significantly lower incidence of infections was seen in the ultra-low-dose groups compared with the standard dose group (1·10 infections per patient-year with the 1000 mg dose vs 0·52 per patient-year with the 500 mg dose and 0·51 per patient-year with the 200 mg dose; rate ratio 0·47, 95% CI 0·21-0·83; p=0·013 for 500 mg vs 1000 mg; 0·44, 0·22-0·88; p=0·019 for 200 mg vs 1000 mg). INTERPRETATION: Our study did not show non-inferiority of ultra-low doses of rituximab for continued treatment of patients with rheumatoid arthritis. Nonetheless, in clinical practice, a strategy with an ultra-low dose of rituximab might be considered after evaluation of risks and benefits, although further studies are needed to establish non-inferiority. Further analyses and a 2-year observational extension are ongoing and should provide further insight into efficacy and safety. FUNDING: Menzis and Centraal Ziekenfonds.

Scleroderma renal crisis and renal involvement in systemic sclerosis.

This corrects the article DOI: 10.1038/nrneph.2016.124.

Validation of Sonography findings of synovitis and tenosynovitis of hands and wrists in patients with systemic sclerosis.

Objectives: Validating musculoskeletal ultrasound features of the joints and tendons of the hands in a large scleroderma cohort. Methods: A total of 81 scleroderma patients participated in this prospective, cross-sectional study. Grayscale and power Doppler musculoskeletal ultrasound images of 13 joints and 5 tendons of the wrist and hand were obtained. Clinical assessment included modified Rodnan skin thickness score, joint count, and Scleroderma Health Assessment Questionnaire. Face validity, content validity, construct validity, and feasibility were assessed. Results: Mean age was 53.8 years (range 22-80), 76.5% were females, and disease duration ranged from 0.25 to 29 years. Mean length of the examination was 36 min. Scleroderma Health Assessment Questionnaire-Disability Index correlated with musculoskeletal ultrasound erosions (r = 0.5, p = 0.0003). Skin score correlated with tendinitis grayscale (r = 0.26, p = 0.02). Intra-reader correlation coefficient for musculoskeletal ultrasound was 0.96 for the joints and could not be calculated for tendons because there were too few positive findings. When tendon changes existed, percent of agreement was 77.7%-83.3%. Conclusion: Musculoskeletal ultrasound of 13 joints and 5 tendons of the hands and wrist has face and content validity. Construct validity was shown for the tendons and erosion scores. Feasibility and reliability were partially validated.

Content and Construct Validity, Reliability, and Responsiveness of the Rheumatoid Arthritis Flare Questionnaire: OMERACT 2016 Workshop Report.

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis (RA) Flare Group was established to develop a reliable way to identify and measure RA flares in randomized controlled trials (RCT). Here, we summarized the development and field testing of the RA Flare Questionnaire (RA-FQ), and the voting results at OMERACT 2016. METHODS: Classic and modern psychometric methods were used to assess reliability, validity, sensitivity, factor structure, scoring, and thresholds. Interviews with patients and clinicians also assessed content validity, utility, and meaningfulness of RA-FQ scores. RESULTS: People with RA in observational trials in Canada (n = 896) and France (n = 138), and an RCT in the Netherlands (n = 178) completed 5 items (11-point numerical rating scale) representing RA Flare core domains. There was moderate to high evidence of reliability, content and construct validity, and responsiveness. Factor analysis supported unidimensionality. Rasch analysis showed acceptable fit to the Rasch model, with items and people covering a broad measurement continuum and evidence of appropriate targeting of items to people, ordered thresholds, minimal differential item functioning by language, sex, or age. A summative score across items is defensible, yielding an interval score (0-50) where higher scores reflect worsening flare. The RA-FQ received endorsement from 88% of attendees that it passed the OMERACT Filter 2.0 "Eyeball Test" for instrument selection. CONCLUSION: The RA-FQ has been developed to identify and measure RA flares. Its review through OMERACT Filter 2.0 shows evidence of reliability, content and construct validity, and responsiveness. These properties merit its further validation as an outcome for clinical trials.

An OMERACT Initiative Toward Consensus to Identify and Characterize Candidate Contextual Factors: Report from the Contextual Factors Working Group.

OBJECTIVE: The importance of contextual factors (CF) for appropriate patient-specific care is widely acknowledged. However, evidence in clinical trials on how CF influence outcomes remains sparse. The 2014 Outcome Measures in Rheumatology (OMERACT) Handbook introduced the role of CF in outcome assessment and defined them as "potential confounders and/or effect modifiers of outcomes in randomized controlled trials." Subsequently, the CF Methods Group (CFMG) was formed to develop guidance on how to address CF in clinical trials. METHODS: First, the CFMG conducted an e-mail survey of OMERACT working groups (WG) to analyze how they had addressed CF in outcome measurement so far. The results facilitated an informed discussion at the OMERACT 2016 CFMG Special Interest Group (SIG) session, with the aim of gaining preliminary consensus regarding an operational definition of CF and to make a first selection of potentially relevant CF. RESULTS: The survey revealed that the WG had mostly used the OMERACT Handbook and/or the International Classification of Functioning, Disability and Health (ICF) definition. However, significant heterogeneity was found in the methods used to identify, refine, and categorize CF candidates. The SIG participants agreed on using the ICF as a framework along with the OMERACT Handbook definition. A list with 28 variables was collected including person-related factors and physical and social environments. Recommendations from the SIG guided the CFMG to formulate 3 preliminary projects on how to identify and analyze CF. CONCLUSION: New methods are urgently needed to assist researchers to identify and characterize CF that significantly influence the interpretation of results in clinical trials. The CFMG defined first steps to develop further guidance.

Clinical meaning and implications of serum hemoglobin levels in patients with rheumatoid arthritis.

OBJECTIVE: Anemia is a common problem in rheumatoid arthritis (RA), associated with radiographic progression and disability. We explored the association of hemoglobin with a comprehensive set of variables in RA patients. METHODS: We included RA outpatients in the routine setting. For each patient we performed measurements (clinical measures, blood tests including serology, markers of acute phase response and iron metabolism, including hepcidin, and circulating hematopoietic precursor levels) at baseline and 12 weeks thereafter, and analyzed their changes in patients with a treatment adaptation at baseline. We performed principal component analysis (PCA) to identify thematic groups hemoglobin was related to. Then we constructed multivariable linear models to assess the contribution of individual variables to the variability of hemoglobin. RESULTS: In total, 88 patients were included (age: 58 ± 12; disease duration: 9.3 ± 9.6 years). Cross-sectionally (at baseline and week 12) hemoglobin levels were tied to iron metabolism and hematopoiesis, but not to clinical activity, based on thematic groups extracted from the PCA. In contrast, longitudinal changes in hemoglobin levels were closely linked to changes in clinical activity. Conversely, hepcidin reflected iron metabolism cross-sectionally, but changes in acute phase response longitudinally. In multivariable analysis variability components of hemoglobin were explainable by ferritin, ESR, evaluator global assessment (EGA), and iron levels, while components of hemoglobin changes were explained by changes in EGA mostly. Hepcidin was not independently associated with hemoglobin. CONCLUSION: Besides its dependence on body iron status, changes in hemoglobin levels are strongly tied to disease activity, possibly revealing more about disease activity than other laboratory markers.

Examining the validity of the rheumatoid arthritis magnetic resonance imaging score according to the OMERACT filter-a systematic literature review.

Objective: To examine whether the RA MRI score (RAMRIS) for RA of the wrist/hand meets the OMERACT filter criteria-truth (validity), discrimination and feasibility. Methods: We conducted a systematic literature review in PubMed and Scopus, from 1970 through June 2014, focused on MRI measures of synovitis, osteitis/bone marrow oedema, erosions and/or joint space narrowing in RA randomized controlled trials and observational studies with cohort size ⩾10. Strength of evidence was assessed using the Cochrane Handbook criteria. Results: Of 634 MRI titles/abstracts, 202 met the review criteria, with 92 providing at least 1 type of validity. Four articles provided criterion validity, and 26 articles utilized RAMRIS to assess 1.5 T MRI images. Histopathology data showed inflammation corresponding to MRI of synovitis and osteitis. MRI erosions corresponded to those identified with CT. Content and construct validity for RAMRIS synovitis, osteitis and erosions were documented by correlations with clinical, laboratory and/or radiographic data. Each measure was sensitive to change and responsive to therapy. RAMRIS synovitis and osteitis were able to discriminate between the efficacy of treatments vs placebo in 12-week studies, whereas RAMRIS erosions required studies of ⩾24 weeks. Conclusion: RAMRIS synovitis, osteitis and erosions imaged with 1.5 T MRI are valid and useful for evaluating joint inflammation and damage for RA of the wrist/hand, according to the OMERACT filter.

Developing an OMERACT Core Outcome Set for Assessing Safety Components in Rheumatology Trials: The OMERACT Safety Working Group.

OBJECTIVE: Failure to report harmful outcomes in clinical research can introduce bias favoring a potentially harmful intervention. While core outcome sets (COS) are available for benefits in randomized controlled trials in many rheumatic conditions, less attention has been paid to safety in such COS. The Outcome Measures in Rheumatology (OMERACT) Filter 2.0 emphasizes the importance of measuring harms. The Safety Working Group was reestablished at the OMERACT 2016 with the objective to develop a COS for assessing safety components in trials across rheumatologic conditions. METHODS: The safety issue has previously been discussed at OMERACT, but without a consistent approach to ensure harms were included in COS. Our methods include (1) identifying harmful outcomes in trials of interventions studied in patients with rheumatic diseases by a systematic literature review, (2) identifying components of safety that should be measured in such trials by use of a patient-driven approach including qualitative data collection and statistical organization of data, and (3) developing a COS through consensus processes including everyone involved. RESULTS: Members of OMERACT including patients, clinicians, researchers, methodologists, and industry representatives reached consensus on the need to continue the efforts on developing a COS for safety in rheumatology trials. There was a general agreement about the need to identify safety-related outcomes that are meaningful to patients, framed in terms that patients consider relevant so that they will be able to make informed decisions. CONCLUSION: The OMERACT Safety Working Group will advance the work previously done within OMERACT using a new patient-driven approach.

Scleroderma renal crisis and renal involvement in systemic sclerosis.

Scleroderma renal crisis (SRC) is a rare, potentially life-threatening complication that affects 2-15% of patients with systemic sclerosis (SSc, also known as scleroderma). SRC typically presents in patients with early, rapidly progressive, diffuse cutaneous SSc within the first 3-5 years after the onset of a non-Raynaud sign or symptom. SRC is characterized by an acute, usually symptomatic increase in blood pressure, a rise in serum creatinine levels, oliguria and thrombotic microangiopathy in about 50% of patients. The prognosis of SRC substantially improved in the 1980s with the introduction of angiotensin-converting-enzyme inhibitors for rapid blood pressure control, with additional antihypertensive agents as required. However, the survival of patients with SRC can still be improved. Current patient survival is 70-82% at 1 year, but decreases to 50-60% at 5 years despite dialysis support. Patients with SRC who show no signs of renal functional recovery despite timely blood pressure control are candidates for transplantation. In this Review, we discuss progress made in the identification and proactive management of patients at risk of SRC and make recommendations aimed at optimizing management for those who progress to chronic kidney failure.