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To assess efficacy, safety, pharmacokinetics, and immunogenicity of pegloticase plus methotrexate (MTX) versus pegloticase plus placebo cotreatment for uncontrolled gout in a randomized, placebo-controlled, double-blind trial.This study included adults with uncontrolled gout, defined as serum urate ≥7 mg/dl, oral urate-lowering therapy failure or intolerance, and presence of ongoing gout symptoms including ≥1 tophus, ≥2 flares in the past 12 months, or gouty arthritis. Key exclusion criteria included MTX contraindication, current immunosuppressant use, G6PDH deficiency, and estimated glomerular filtration rate40 ml/minute/1.73 mA total of 152 patients were randomized, 100 to receive pegloticase plus MTX, 52 to receive pegloticase plus placebo. Significantly higher treatment response occurred during month 6 in the MTX group versus the placebo group (71.0% [71 of 100 patients] versus 38.5% [20 of 52 patients], respectively; between-group difference 32.3% [95% confidence interval 16.3%, 48.3%]) (P 0.0001 for between-group difference). During the first 6 months of pegloticase plus MTX or pegloticase plus placebo treatment, 78 (81.3%) of 96 MTX patients versus 47 (95.9%) of 49 placebo patients experienced ≥1 adverse event (AE), most commonly gout flare (64 [66.7%] of 96 MTX patients and 34 [69.4%] of 49 placebo patients). Reports of AEs and serious AEs were comparable between groups, but the infusion reaction rate was considerably lower with MTX cotherapy (4.2% [4 of 96 MTX patients, including 1 patient who had anaphylaxis]) than with placebo cotherapy (30.6% [15 of 49 placebo patients, 0 who had anaphylaxis]) (P 0.001). Antidrug antibody positivity was also lower in the MTX group.MTX cotherapy markedly increased pegloticase response rate over placebo (71.0% versus 38.5%) during month 6 with no new safety signals. These findings verify higher treatment response rate, lower infusion reaction incidence, and lower immunogenicity when pegloticase is coadministered with MTX.

ObjectivesTo investigate temporal trends in incidence and severity of COVID-19 among patients with systemic autoimmune rheumatic diseases (SARDs) from the first wave through the initial Omicron wave.MethodsWe conducted a retrospective cohort study investigating COVID-19 outcomes among patientswith SARD systematically identified to have confirmed COVID-19 from 1 March 2020 to 31 January 2022 at Mass General Brigham. We tabulated COVID-19 counts of total and severe cases (hospitalisations or deaths) and compared the proportion with severe COVID-19 by calendar period and by vaccination status. We used logistic regression to estimate the ORs for severe COVID-19 for each period compared with the early COVID-19 period (reference group).ResultsWe identified 1449 patients with SARD with COVID-19 (mean age 58.4 years, 75.2% female, 33.9% rheumatoid arthritis). There were 399 (28%) cases of severe COVID-19. The proportion of severe COVID-19 outcomes declined over calendar time (p for trend ConclusionsThe proportion of patients with SARD with severe COVID-19 has diminished since early in the pandemic, particularly during the most recent time periods, including the initial Omicron wave. Advances in prevention, diagnosis and treatment of COVID-19 may have improved outcomes among patients with SARD.

The biologics abatacept and adalimumab have different mechanisms of action (MoAs). We analyzed data from patients with rheumatoid arthritis treated in AMPLE (NCT00929864) to explore the pharmacodynamic effects of abatacept or adalimumab on anti-citrullinated protein antibodies (ACPAs) and gene expression.AMPLE was a phase IIIb, 2-year, randomized, head-to-head trial of abatacept versus adalimumab. Post hoc analyses of baseline anti-cyclic citrullinated peptide-2 (anti-CCP2, an ACPA surrogate) positive (+) status and ACPA fine-specificity profiles over time, as well as transcriptional profiling (peripheral whole blood), were performed.Of 646 patients treated (abatacept, n = 318; adalimumab, n = 328), ACPA and gene expression data were available from 508 and 566 patients, respectively. In anti-CCP2+ patients (n = 388), baseline fine specificities for most ACPAs were highly correlated; over 2 years, levels decreased with abatacept but not adalimumab. By year 2, expression of genes associated with T cell co-stimulation and antibody production was lower for abatacept versus adalimumab; expression of genes associated with proinflammatory signaling was lower for adalimumab versus abatacept. Treatment modulated the expression of T- and B-cell gene signatures, with differences in CD8+ T cells, activated T cells, plasma cells, B cells, natural killer cells (all lower with abatacept versus adalimumab), and polymorphonuclear leukocytes (higher with abatacept versus adalimumab).In AMPLE, despite similar clinical outcomes, data showed that pharmacodynamic/genetic changes after 2 years of abatacept or adalimumab were consistent with drug MoAs. Further assessment of the relationship between such changes and clinical outcomes, including prediction of response, is warranted.ClinicalTrials.gov identifier, NCT00929864.

Objectives Pulmonary disease is a common extraarticular manifestation of RA associated with increased morbidity and mortality. No current strategies exist for screening this at-risk population for parenchymal lung disease, including emphysema and interstitial lung disease (ILD). Methods RA patients without a diagnosis of ILD or chronic obstructive pulmonary disease underwent prospective and comprehensive clinical, laboratory, functional and radiological evaluations. High resolution CT (HRCT) scans were scored for preclinical emphysema and preclinical ILD and evaluated for other abnormalities. Results Pulmonary imaging and/or functional abnormalities were identified in 78 (74%) of 106 subjects; 45% had preclinical parenchymal lung disease. These individuals were older with lower diffusion capacity but had similar smoking histories compared with no disease. Preclinical emphysema (36%), the most commonly detected abnormality, was associated with older age, higher anti-cyclic citrullinated peptide antibody titres and diffusion abnormalities. A significant proportion of preclinical emphysema occurred among never smokers (47%) with a predominantly panlobular pattern. Preclinical ILD (15%) was not associated with clinical, laboratory or functional measures. Conclusion We identified a high prevalence of undiagnosed preclinical parenchymal lung disease in RA driven primarily by isolated emphysema, suggesting that it may be a prevalent and previously unrecognized pulmonary manifestation of RA, even among never smokers. As clinical, laboratory and functional evaluations did not adequately identify preclinical parenchymal abnormalities, HRCT may be the most effective screening modality currently available for patients with RA.

Aims : Patients with rheumatoid arthritis (RA) have an increased risk of venous thromboembolism (VTE), likely related to underlying inflammation. We examined VTE risk associated with two commonly used immunomodulators in RA patients, methotrexate and hydroxychloroquine. Methods and Results : Using U.S. Medicare claims data (2008-2017), we identified RA patients (≥65 years) who initiated methotrexate or hydroxychloroquine without prior use of any immunomodulators. The primary outcome was VTE, a composite of pulmonary embolism (PE) or deep vein thrombosis (DVT). Secondary outcomes included PE, DVT, and all-cause mortality. After 1:1 propensity score matching for confounding control, we identified 26,534 pairs of methotrexate and hydroxychloroquine initiators (mean (SD) age 74 (7) years; 79% female). During a total of 56,686 person-years of follow-up, 208 methotrexate and 83 hydroxychloroquine initiators developed VTE. The incidence rate of VTE was higher among methotrexate initiators (6.94/1,000 person-years) than hydroxychloroquine initiators (3.11/1,000 person-years) with a hazard ratio (HR) of 2.26 (95%CI 1.75, 2.91). Methotrexate initiators had a greater risk of PE (HR 3.30, 95%CI 2.28, 4.77) and DVT (HR 1.53, 95%CI 1.07, 2.19) than hydroxychloroquine initiators. All-cause mortality was similar between the two groups (HR 0.91, 95%CI 0.83, 1.00). Conclusion : In this large real-world cohort of older RA patients, treatment with methotrexate was associated with a 2-fold increased risk of VTE relative to hydroxychloroquine, although all-cause mortality was similar. Future experimental studies with non-user control groups are needed to determine the causal relationships between the study drugs and VTE and whether methotrexate elevates or hydroxychloroquine reduces the risk of VTE.

ObjectiveTo investigate temporal trends, severe outcomes, and rebound among systemic autoimmune rheumatic disease (SARD) patients according to outpatient SARS-CoV-2 treatment.MethodsWe performed a retrospective cohort study investigating outpatient SARS-CoV-2 treatments among SARD patients at Mass General Brigham (23/Jan/2022-30/May/2022). We identified SARS-CoV-2 infection by positive PCR or antigen test (index date=first positive test) and SARDs using diagnosis codes and immunomodulator prescription. Outpatient treatments were confirmed by medical record review. The primary outcome was hospitalization or death within 30 days following the index date. COVID-19 rebound was defined as documentation of negative then newly-positive SARS-CoV-2 tests. The association of any vs. no outpatient treatment with hospitalization/death was assessed using multivariable logistic regression.ResultsWe analyzed 704 SARD patients with COVID-19 (mean age 58.4 years, 76% female, 49% with rheumatoid arthritis). Treatment as outpatient increased over calendar time (pConclusionOutpatient treatment was strongly associated with lower odds of severe COVID-19 compared to no outpatient treatment. At least 8% of SARD patients experienced COVID-19 rebound. These findings highlight the importance of outpatient COVID-19 treatment for SARD patients and the need for further research on rebound.KEY MESSAGESWhat is already known on this topic?Previous studies suggest that monoclonal antibodies are an effective outpatient treatment option for patients at high-risk of severe COVID-19, including those with systemic autoimmune rheumatic diseases (SARDs).Nirmatrelvir/ritonavir and molnupiravir are recently-authorized effective oral outpatient SARS-CoV-2 treatment options, but clinical trials were performed among the general population, mostly among unvaccinated and prior to Omicron viral variants.Oral outpatient SARS-CoV-2 treatments may result in COVID-19 rebound, characterized by newly-positive COVID-19 testing and recurrent symptoms, but no studies have investigated rebound prevalence among SARD patients.What this study adds?This is one of the first studies investigating outpatient SARS-CoV-2 treatments among SARD patients that includes oral options and quantifies the prevalence of COVID-19 rebound.Outpatient treatment was associated with 88% reduced odds of severe COVID-19 compared to no treatment.At least 8% of SARDs receiving oral outpatient treatment experienced COVID-19 rebound.How this study might affect research, practice, or policy?These results should encourage clinicians to prescribe and SARD patients to seek prompt outpatient COVID-19 treatment.This research provides an early estimate of the prevalence of COVID-19 rebound after oral outpatient treatment to quantify this risk to clinicians and SARD patients and encourage future research.

Objective Guidelines for methotrexate (MTX) use in rheumatic disease may not be feasible for physicians practicing in the least developed countries. We aimed to understand the experiences of MTX prescribers relating to MTX use for rheumatic disease in African countries to inform the development of culturally and geographically appropriate recommendations. Methods African physicians who self‐identified as MTX prescribers from countries classified as having a low versus a medium or high Human Development Index (L‐HDI versus MH‐HDI) participated in semistructured interviews between August 2016 and September 2017. Interviews were transcribed verbatim, coded thematically, and stratified by HDI. Results Physicians (23 rheumatologists; six internists) from 29 African countries were interviewed (15 L‐HDI; 14 MH‐HDI). Identified barriers to MTX use included inconsistent MTX supply (reported by 87% L‐HDI versus 43% MH‐HDI), compounded by financial restrictions (reported by 93% L‐HDI versus 64% MH‐HDI), patient hesitancy based partly on cultural beliefs and societal roles (reported by 71%), few prescribers (reported by 33%), prevalent infections (especially viral hepatitis, tuberculosis, and human immunodeficiency virus), and both availability and cost of monitoring tests. MTX pretreatment evaluation and starting and maximal doses were similar between L‐HDI countries and MH‐HDI countries. Conclusion The challenges of treating rheumatic disease in African countries include unreliable drug availability and cost, limited subspecialists, and patient beliefs. Adapting recommendations for MTX use in the context of prevalent endemic infections; ensuring safe but feasible MTX monitoring strategies, enhanced access to stable drug supply, and specialized rheumatology care; and improving patient education are key to reducing the burden of rheumatic diseases in L‐HDI countries.

Objective Patients with rheumatoid arthritis (RA) are 1.5 times more likely to develop cardiovascular disease (CVD) attributed to chronic inflammation. A decrease in inflammation in patients with RA is associated with increased low-density lipoprotein (LDL) cholesterol. This study was undertaken to prospectively evaluate the changes in lipid levels among RA patients experiencing changes in inflammation and determine the association with concomitant temporal patterns in markers of myocardial injury. Methods A total of 196 patients were evaluated in a longitudinal RA cohort, with blood samples and high-sensitivity C-reactive protein (hsCRP) levels measured annually. Patients were stratified based on whether they experienced either a significant increase in inflammation (an increase in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the increased inflammation cohort [n = 103]) or decrease in inflammation (a decrease in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the decreased inflammation cohort [n = 93]). Routine and advanced lipids, markers of inflammation (interleukin-6, hsCRP, soluble tumor necrosis factor receptor II), and markers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT], N-terminal pro-brain natriuretic peptide) were measured. Results Among the patients in the increased inflammation cohort, the mean age was 59 years, 81% were women, and the mean RA disease duration was 17.9 years. The average increase in hsCRP levels was 36 mg/liter, and this increase was associated with significant reductions in LDL cholesterol, triglycerides, total cholesterol, apolipoprotein (Apo B), and Apo A-I levels. In the increased inflammation cohort at baseline, 45.6% of patients (47 of 103) had detectable circulating hs-cTnT, which further increased during inflammation (P = 0.02). In the decreased inflammation cohort, hs-cTnT levels remained stable despite a reduction in inflammation over follow-up. In both cohorts, hs-cTnT levels were associated with the overall estimated risk of CVD. Conclusion Among RA patients who experienced an increase in inflammation, a significant decrease in routinely measured lipids, including LDL cholesterol, and an increase in markers of subclinical myocardial injury were observed. These findings highlight the divergence in biomarkers of CVD risk and suggest a role in future studies examining the benefit of including hs-cTnT for CVD risk stratification in RA.

Objective We aimed to determine the real-world prevalence and investigate risk factors for rheumatoid arthritis (RA)-related lung disease on chest computed tomography (CT) imaging. We also investigated the impact of RA-related lung disease on mortality. Methods We studied chest CT imaging abnormalities among RA patients. We determined the presence and type of abnormalities using the chest CT imaging radiologic report. RA-related lung disease was defined as interstitial lung disease (ILD), bronchiectasis, or pleural disease. We examined whether demographics and RA characteristics were associated with RA-related lung disease using logistic regression. RA-related lung disease and mortality was described using survival curves and Cox regression. Results We analyzed 190 patients who had chest CT imaging performed for clinical indications. Mean age was 64.2 years (SD 11.8), 80.0% were female, and 75.3% were seropositive. RA-related lung disease was detected in 54 patients (28.4%); 30 (15.8%) had ILD, 27 (14.2%) had bronchiectasis, and 18 (9.5%) had pleural disease. RA-related lung disease was reported in both seropositive and seronegative RA (28.7% vs. 27.7%, p = 1.00). Male sex (OR 2.62, 95%CI 1.17–5.88) and current methotrexate use (OR 2.73, 95%CI 1.27–5.61 vs. not current) were associated with RA-related lung disease. Twenty-four (44.4%) patients with RA-related lung disease died during mean 7.0 years of follow-up. RA-related lung disease had HR of 5.35 (95%CI 0.72–39.9) for mortality compared to normal chest CT. Conclusions In this real-world study, RA-related lung disease was commonly detected on chest CT imaging regardless of RA serostatus. RA-related lung disease had high mortality, emphasizing the importance in close monitoring of these patients.

Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries. It is unknown whether they are relevant globally. We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs).Electronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. Reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument for study quality assessment. Similarities and discrepancies of recommendations are reported.After deduplication, 1693 unique citations were found; 25 full texts were screened and 12 included in the narrative synthesis. Average scores for the AGREE II domains ranged from 33.3 to 83.3%. Recommendations targeted rheumatologists and health care providers involved in RA care. Most covered some but not all of the following areas: baseline "pre-MTX" assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). Recommendations agreed on baseline tests prior to starting MTX, monitoring, and need for folic acid supplementation. These aspects can serve as the foundation for the development of MTX recommendations relevant to LDCs. Recommendations disagreed on the MTX starting dose, optimal route, titration, and intervals to monitor toxicity.Existing recommendations do not uniformly address all aspects related to the use of MTX and disagree in relevant aspects of MTX use. Adaptations to these recommendations are needed to facilitate their implementation in LDCs. Key Points • This paper summarizes current recommendations on the use of methotrexate for the treatment of rheumatoid arthritis. • Areas of agreement between recommendations include the following: pre-methotrexate patient assessment, need for folic acid supplementation, and toxicity monitoring. • Areas of disagreement relate to methotrexate starting and maximal dose, titration, and frequency of assessments.

Objective Phase III clinical trials of the tumour necrosis factor inhibitors SB4, SB2, and SB5 (biosimilars to etanercept, infliximab, and adalimumab, respectively) have demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA). Data from these trials were used to identify baseline characteristics associated with radiographic progression and to build a matrix risk model for its prediction. Methods Patients with radiographic progression and baseline demographic and disease characteristic data were pooled across the 3 phase III studies of each biosimilar and its reference product. Baseline demographics and disease characteristics were evaluated for their relationship with radiographic progression (1-year mean change in mTSS > 0); 3 factors were selected based on strongest Pearson’s correlation coefficient with the change in modified Total Sharp Score. Univariate logistic regression was performed to assess the association between each baseline factor and the rate of radiographic progression, with subsequent matrix model development performed using multivariate logistic regression. Results A total of 1371 patients were included in the analysis, with a radiographic progression rate of 27.4%. The 3 baseline predictors of radiographic progression, based on Pearson’s correlation coefficient, were 28 swollen joint count (SJC28), C-reactive protein (CRP), and physician global assessment (PhGA). A matrix model showed that the predicted risk of radiographic progression was higher with the increased level of SJC28, CRP, and PhGA (P Conclusions In this pooled analysis of phase III clinical trial data of biosimilars for RA, identifiable baseline factors (SJC28, CRP, and PhGA) associated with radiographic progression were similar to those described in prior studies. Even though radiographic progression was minimal, a small number of patients who have increased SJC28, CRP, and PhGA at baseline should be closely monitored and follow treat-to-target approach. Clinical trial registration numbers EudraCT 2012-005026-30. Registered 30 April 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005026-30/results EudraCT 2012-005733-37. Registered 10 July 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005733-37/results EudraCT 2013-005013-13. Registered 01 April 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005013-13/results

Objective Patients with rheumatoid arthritis (RA) and other systemic rheumatic diseases (SRDs) are at increased risk of developing herpes zoster (HZ). Zoster recombinant adjuvanted (ZRA) is a recombinant vaccine approved by the Food and Drug Administration in 2018. Concern has been raised that the ZRA may trigger disease flares in rheumatology patients who are immunocompromised. We investigated the impact of the ZRA vaccine in patients with RA and SRD and measured the incidence of flares and side effects. Methods A flare was defined as occurring within 12 weeks of vaccine administration by either 1) documentation of RA flare in office notes, telephone encounter, or patient portal communication or 2) new or increased dose of corticosteroids. Results We identified 403 patients (239 patients with RA and 164 patients with SRD) who received the ZRA vaccine from February 1, 2018, to February 1, 2019. We measured a 6.7% (n = 27) incidence of flare. Side effects occurred in 12.7% (n = 51) of patients. All flares and side effects were regarded as mild. Three cases of HZ were reported as occurring 2, 10, and 11 months after the vaccination. Conclusion In 403 patients who received the ZRA vaccine, the incidence of disease flares was 7% or less and that of side effects was 13% or less, both of which are less than the incidence rates observed in the pivotal trials.

OBJECTIVE Seropositivity for anti-citrullinated protein antibody (ACPA)/rheumatoid factor (RF) in rheumatoid arthritis (RA) is associated with increased overall mortality; however, the association between antibody titers and mortality is not well established. Investigating relationships between antibody titers and mortality may clarify their role in RA pathogenesis. This study was undertaken to evaluate the association of antibody titers with mortality and its modification by disease-modifying antirheumatic drugs (DMARDs). METHODS Eligible patients with established RA were identified through administrative claims data linked to laboratory results (2005-2016). Patients were categorized by positivity status for ACPA, RF, or both. Patients were further divided into groups by autoantibody titers. DMARD-exposed patients were categorized into biologic DMARD (bDMARD) and conventional DMARD (cDMARD) subcohorts. Crude mortality rates/1,000 patient-years and Kaplan-Meier curves were compared between antibody categories. Adjusted Cox proportional hazards regression and sensitivity (propensity-matched patients) analyses were conducted. RESULTS Overall, 53,849 and 79,926 patients had evaluable ACPA and RF status, respectively. For both autoantibodies, mortality rates were significantly higher in seropositive versus seronegative patients (risk increase of 48.0% and 44.0% in ACPA- and RF-positive patients, respectively; P < 0.001 each). Mortality rates were greatest in patients with higher versus lower autoantibody titers (ACPA hazard ratio [HR] 1.60 [95% confidence interval (95% CI]) 1.45-1.76]; RF HR 1.78 [95% CI 1.66-1.91]). In cDMARD-exposed patients, HRs were higher in seropositive versus seronegative cohorts; in bDMARD-exposed patients, there was no difference in mortality by serostatus. CONCLUSION Elevated ACPA/RF titers were independently associated with increased mortality among patients with RA and persisted in patients treated with cDMARDs but not with bDMARDs.

To characterise the incidence rate of skin cancer associated with methotrexate and hydroxychloroquine in older adults with rheumatoid arthritis (RA).RA patients aged ≥65 years who initiated methotrexate or hydroxychloroquine as their first disease modifying antirheumatic drugs (DMARDs). The primary outcome was new occurrence of any skin cancer (i.e. malignant melanoma or non-melanoma skin cancer; NMSC) based on validated algorithms (positive predictive value83%). Secondary outcomes were malignant melanoma, NMSC, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). We estimated the incidence rates (IRs) and hazard ratios (HRs) for each outcome in the 1:1 propensity score (PS)-matched methotrexate and hydroxychloroquine groups.We included 24,577 PS-matched pairs of methotrexate and hydroxychloroquine initiators. Compared with hydroxychloroquine (IR 25.20/1,000 person-years), methotrexate initiators (IR 26.21/1,000 person-years) had a similar risk of any skin cancer [HR 1.03 -(95%CI 0.92, 1.14)] over a mean follow-up of 388 days. The HR (95%CI) associated with methotrexate was 1.39 (0.87, 2.21) for malignant melanoma, 1.01(0.90, 1.12) for NMSC, 1.37 (1.13, 1.66) for BCC, and 0.79 (0.63, 0.99) for SCC compared with hydroxychloroquine.In this large cohort of older RA patients initiating methotrexate or hydroxychloroquine as their first DMARD, we found no difference in the risk of skin cancer including malignant melanoma and NMSC. However, for specific components of NMSC, methotrexate initiators had higher risk of BCC but lower risk of SCC compared with hydroxychloroquine initiators.

Shared epitope (SE) is present in high proportions of anti-citrullinated protein antibody (ACPA) + patients with rheumatoid arthritis (RA) and is associated with poor prognosis. We assessed the role of SE in RA prognosis, in relation to ACPA positivity.Patients enrolled in the Brigham and Women's RA Sequential Study were included. Changes from baseline in disease activity (Disease Activity Score in 28 joints using C-reactive protein [DAS28 (CRP)], Clinical Disease Activity Index [CDAI], Simplified Disease Activity Index [SDAI]) to 1 year were assessed. Baseline characteristics were compared by SE and ACPA status (±; chi-squared, Kruskal-Wallis). Association between number of SE alleles and ACPA status (logistic regression models), relationships between baseline characteristics and changes in disease activity (adjusted linear regression model), and effect of ACPA on the association between SE and changes in disease activity (mediation analysis) were studied.Nine hundred twenty-six patients were included. SE + versus SE - patients had significantly longer disease duration and higher disease activity scores and were more likely to have erosive disease, have higher comorbidity burden, and be RF + (all p 0.05). Among patients with one or two SE alleles (vs. 0), odds of being ACPA + were 1.97 (p = 0.0003) and 3.82 (p 0.0001), respectively. SE + versus SE - patients had worse disease activity scores as indicated by mean increases in DAS28 (CRP) of 0.22, CDAI of 2.07, and SDAI of 2.43 over 1 year (all p 0.05). Direct effect of SE + accounted for 76.4-80.1% of total effect in disease activity increases.SE is strongly associated with ACPA positivity and higher disease activity in patients with RA. SE was associated with greater increases in disease activity over 1 year, which was partially mediated by the presence of ACPA.ClinicalTrials.gov identifier: NCT01793103; registration date: February 15, 2013, retrospectively registered.Patients with rheumatoid arthritis (RA) experience inflamed and damaged joints. RA is an autoimmune disease where proteins called autoantibodies in the blood of patients with RA target the patient’s own joint tissue and organs by mistake. This causes inflammation. Patients with certain autoantibodies, such as anti-citrullinated protein antibodies (ACPAs), may experience worse symptoms. There are certain genetic risk factors that may mean a person is more likely to develop RA. One example of a genetic risk factor is having the shared epitope (SE).Our study looked at almost 1000 patients with RA in the general population. It explored the impact of having SE and ACPAs on changes in RA disease activity. Patients with SE had RA for a longer time, had more severe disease, and were more likely to have other diseases compared with patients without SE. Patients with SE were also more likely to have ACPAs. Over the course of one year, patients with SE had larger increases in RA disease activity than those patients without SE, even though they were taking the same treatments. These results suggest that patients with the genetic risk factor, SE often have RA that is harder to treat. Doctors should take this into account when selecting treatment for RA.

Objective To assess the frequency of cardiovascular and venous thromboembolic events in clinical studies of baricitinib, an oral, selective JAK1 and JAK2 inhibitor approved in more than 50 countries for the treatment of moderately‐to‐severely active rheumatoid arthritis (RA). Methods Data were pooled from 9 RA studies. Placebo comparison up to 24 weeks included data from 6 studies. Randomized dose comparison between baricitinib doses of 2 mg and 4 mg used data from 4 studies and from the associated long‐term extension study. The data analysis set designated “All‐bari‐RA” included all baricitinib exposures at any dose. Results Overall, 3,492 RA patients received baricitinib (7,860 patient‐years of exposure). No imbalance compared to the placebo group was seen in the incidence of major adverse cardiovascular events (MACE) (incidence rates [IRs] of 0.5 per 100 patient‐years for placebo and 0.8 per 100 patient‐years for 4 mg baricitinib), arterial thrombotic events (ATE) (IRs of 0.5 per 100 patient‐years for placebo and 0.5 per 100 patient‐years for 4 mg baricitinib), or congestive heart failure (CHF) broad term (IRs of 4.3 per 100 patient‐years for placebo and 2.4 per 100 patient‐years for 4 mg baricitinib). Deep vein thrombosis (DVT)/pulmonary embolism (PE) were reported in 0 of 1,070 patients treated with placebo and 6 of 997 patients treated with 4 mg baricitinib during the placebo‐controlled period; these events were serious in 2 of 6 patients, while all 6 had risk factors and 1 patient developed DVT/PE after discontinuation of the study drug. In the 2 mg–4 mg‐extended data analysis set, IRs of DVT/PE were comparable between the doses across event types (IRs of 0.5 per 100 patient‐years in those receiving 2 mg baricitinib and 0.6 per 100 patient‐years in those receiving 4 mg baricitinib). In the All‐bari‐RA data analysis set, the rates were stable over time, with an IR of DVT/PE of 0.5 per 100 patient‐years. Conclusions In RA clinical trials, no association was found between baricitinib treatment and the incidence of MACE, ATE, or CHF. With regard to incidence of DVT/PE, 6 events occurred in patients treated with 4 mg baricitinib, but no cases of DVT/PE were reported in the placebo group. During longer‐term evaluation, the incidence of DVT/PE was similar between the baricitinib dose groups, with consistent IR values over time, and this was similar to the rates previously reported in patients with RA.

OBJECTIVE To evaluate the risk of venous thromboembolism (VTE) in rheumatoid arthritis (RA) patients receiving tofacitinib versus those receiving tumor necrosis factor (TNF) inhibitors. METHODS RA patients who were initiating treatment with tofacitinib or a TNF inhibitor and had not previously received any biologic agent or tofacitinib were identified from the Truven MarketScan database (2012-2016) or Medicare claims (parts A, B, and D) database (2012-2015). Patients were followed up until treatment discontinuation, treatment switch, insurance disenrollment, or administrative censoring. The outcome of VTE was identified using inpatient claims for pulmonary embolism or deep vein thrombosis. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were determined using a Cox proportional hazards model after accounting for confounding through propensity score-based fine-stratification weighting. HRs were pooled across databases using the inverse variance meta-analytic method. RESULTS A total of 34,074 RA patients (mean age 50 years; 5.6% tofacitinib initiators) and 17,086 RA patients (mean age 71 years; 5.8% tofacitinib initiators) were identified from the Truven and Medicare databases, respectively. The crude incidence rates of VTE per 100 person-years were 0.60 (95% CI 0.26-1.19) and 0.34 (95% CI 0.27-0.41) in Truven and 1.12 (95% CI 0.45-2.31) and 0.92 (95% CI 0.76-1.11) in Medicare for patients receiving tofacitinib and patients receiving TNF inhibitors, respectively. Propensity score-adjusted HRs showed no significant differences in the risk of VTE between tofacitinib-treated and TNF inhibitor-treated patients in either database, with a pooled HR of 1.33 (95% CI 0.78-2.24). CONCLUSION Occurrence of VTE in a total of 50,865 RA patients initiating treatment with tofacitinib or a TNF inhibitor was infrequent (

Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide general guidance for commonly encountered clinical scenarios. The recommendations do not dictate the care for an individual patient. The ACR considers adherence to the recommendations described in this guideline to be voluntary, with the ultimate determination regarding their application to be made by the clinicians in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed and endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice. ACR recommendations are not intended to dictate payment or insurance decisions, or drug formularies or other third-party analyses. Third parties that cite ACR guidelines should state that these recommendations are not meant for this purpose. These recommendations cannot adequately convey all uncertainties and nuances of patient care. The American College of Rheumatology is an independent, professional, medical and scientific society that does not guarantee, warrant, or endorse any commercial product or service. OBJECTIVE. To develop updated guidelines for the pharmacologic management of rheumatoid arthritis. METHODS. We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS. The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional). CONCLUSION. This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients’ values, goals, preferences, and comorbidities.

Introduction Filgotinib (FIL), inhibiteur preferentiel de JAK1 per os, a ameliore les signes et les symptomes de la polyarthrite rhumatoide (PR) dans 3 essais de phase 3. Malgre l’efficacite du FIL et des autres JAKi, il existe certaines incertitudes concernant le risque thromboemboliques veineux (TEV), d’evenements cardiovasculaires majeurs (ECM) et d’elevation des taux de plaquettes, qui pourrait resulter de l’inhibition de JAK2 et de la modulation de la thrombopoietine, et avoir un lien de causalite avec les TEV. Patients et methodes Les patients (pts) des etudes DARWIN1–2, FINCH1–3 et des extensions DARWIN3 et FINCH4 ont ete inclus. Les evenements ont ete analyses en fonction du traitement recu. L’analyse de la tolerance controlee par placebo (PBO) jusqu’a S12 comprenait des donnees provenant de patients ayant recu FIL100, FIL200 ou PBO jusqu’a 12S ; certains pts traites par PBO avaient des donnees supplementaires jusqu’a S24. L’analyse controlee par traitement actif incluait les donnees des patients ayant recu FIL100, FIL200 ou adalimumab (ADA) avec un traitement anterieur par methotrexate (MTX) et des patients ayant recu FIL100 + MTX, FIL200 + MTX, FIL200 ou MTX jusqu’a 52S. L’analyse FIL200 vs FIL100 incluait les donnees des pts jusqu’a 5,5 ans. Les donnees ont ete analysees selon l’apparition ou non d’un ECM ou d’un TEV. Pour l’analyse controlee par traitement actif (sauf ECM dans l’analyse controlee par MTX), les taux d’incidence ajustes en fonction de l’exposition (TIAE) et les IC95 % ont ete calcules a l’aide de la loi de Poisson, et les differences de traitement ont ete fournies avec les IC correspondants, sur la base des limites de confiance des estimations ponctuelles individuelles. Pour les analyses FIL200 vs FIL100 et ECM dans l’analyse controlee par MTX, les TIAE, la difference des TIAE, et les IC95 % ont ete calcules par la regression de Poisson avec le groupe de traitement comme covariable. Les suspicions d’ECM (deces cardiovasculaire (CV), infarctus du myocarde, AVC) et de TEV (thrombose veineuse profonde (TVP) et embolie pulmonaire (EP)) ont ete adjudiquees en aveugle par un comite independant d’evaluation de la tolerance CV. Resultats Les facteurs de risque CV etaient frequents a l’inclusion ( Fig. 1 ). Aucun TEV ne s’est produit pendant la periode controlee par PBO de 12S ( Fig. 2 ). Il y a eu 13 TEV au total. Les TIAE/100 patients-annees d’exposition (PAE) etaient comparables pour tous les traitements (TIAE [n] : FIL200, 0,2 [7] ; FIL100, 0,1 [1] ; ADA, 0,3 [1] ; MTX, 0,5 [2] ; PBO (jusqu’a S24), 0,7 [2] ; Fig. 2 ). L’incidence brute des ECM pendant la periode controlee par PBO est illustree a la Fig. 3 . Il y a eu 32 ECM au total. Les TIAE etaient comparables pour tous les traitements (TIAE [n] : FIL200, 0,6 [16] ; FIL100, 0,6 [10] ; ADA, 0,3 [1] ; MTX, 0,5 [2] ; PBO (jusqu’a S24), 1,0 [3] ; Fig. 3 ). La numeration plaquettaire n’a pas augmente au cours de l’etude. A S52, les taux plaquettaires moyen ont legerement diminue dans tous les bras de traitement. Conclusion Aucun signal de tolerance pour les ECM et les TVE n’a ete observe dans le developpement clinique du FIL dans la PR. Les TIAE des TEV et des ECM etaient faibles et conformes aux taux attendus chez des patients PR (TIAE 0,4/100 PAE pour les TEV et 1,0/100 PAE pour les ECM) [1] , [2] .

Drs. Pincus, Bergman, and Yazici have raised some concerns about our published article comparing the Clinical Disease Activity Index (CDAI) with simultaneous measures of the Routine Assessment of Patient Index Data 3 (RAPID3).1 We believe our publication has clearly established that the validated CDAI scores provide a fundamentally different evaluation of disease status compared with the RAPID3.

Objective To evaluate the risk of venous thromboembolism (VTE) with tofacitinib compared with TNFis in patients with RA. Methods RA patients initiating tofacitinib or a TNFi without use of any biologic or tofacitinib any time prior were identified from IBM ‘MarketScan’ (2012–18), Medicare (parts A, B and D, 2012–17) or ‘Optum’ Clinformatics (2012–19) and followed until treatment discontinuation, treatment switch, insurance disenrollment or administrative censoring. The primary outcome, VTE, was identified using inpatient claims for pulmonary embolism or deep vein thrombosis. A Cox proportional hazards model provided hazard ratio (HR) and 95% CIs after accounting for confounding through propensity score fine-stratification weighting. HRs were pooled across databases with inverse variance meta-analytic method. Results A total of 42 201, 25 078 and 20 374 RA patients were identified from MarketScan, Medicare and Optum, respectively, of whom 7.1, 7.1 and 9.7% were tofacitinib initiators. The crude incidence rates per 100 person-years (95% CI) were 0.42 (0.20–0.77) and 0.35 (0.29–0.42) in MarketScan, 1.18 (0.68–1.92) and 0.83 (0.71–0.97) in Medicare, and 0.19 (0.04–0.57) and 0.34 (0.26–0.44) in Optum for tofacitinib and TNFis, respectively. Propensity score-weighted HRs showed no significant differences in the risk of VTE between tofacitinib and TNFis in any database with a pooled HR (95% CI) of 1.13 (0.77–1.65). Conclusion Overall, VTE occurred infrequently (

Background The multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors. Methods Four cohorts were analyzed: the BRASS and Leiden registries and the OPERA and SWEFOT studies (total N = 953). Treatments included conventional DMARDs and anti-TNFs. Associations of radiographic progression (ΔTSS) per year with the adjusted MBDA score, seropositivity, and clinical measures were evaluated using linear and logistic regression. The adjusted MBDA score was (1) validated in Leiden and SWEFOT, (2) compared with other measures in all four cohorts, and (3) used to generate curves for predicting risk of radiographic progression. Results Univariable and bivariable analyses validated the adjusted MBDA score and found it to be the strongest, independent predicator of radiographic progression (ΔTSS > 5) compared with seropositivity (rheumatoid factor and/or anti-CCP), baseline TSS, DAS28-CRP, CRP SJC, or CDAI. Neither DAS28-CRP, CDAI, SJC, nor CRP added significant information to the adjusted MBDA score as a predictor, and the frequency of radiographic progression agreed with the adjusted MBDA score when it was discordant with these measures. The rate of progression (ΔTSS > 5) increased from Conclusion The adjusted MBDA score was validated as an RA disease activity measure that is prognostic for radiographic progression. The adjusted MBDA score was a stronger predictor of radiographic progression than conventional risk factors, including seropositivity, and its prognostic ability was not significantly improved by the addition of DAS28-CRP, CRP, SJC, or CDAI.

ObjectiveIn patients with rheumatoid arthritis (RA) with low 28-joint tender and swollen joint counts but who assessed their disease as active, to evaluate whether activity reflected RA symptoms.MethodsWe carried out a cross-sectional study of patients in BRASS, a cohort of patients with established RA who had 28-joint counts assessed, scored their disease activity, identified their painful joints, and answered questions about other sites of pain and fatigue. Patients and their rheumatologists were asked about the presence of fibromyalgia. We examined whether patients reported pain in joints excluded from the 28-joint joint count (feet, ankles, hips, neck) and pain or symptoms probably unrelated to RA including low back pain, headache and fibromyalgia. Fatigue was not classified. Analyses were descriptive.ResultsOf 272 patients, 49 had tender and swollen joint counts ConclusionIf joint counts

ObjectiveTo determine the association between novel lifestyle factors on risk of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD), define the threshold at which smoking increases RA-ILD risk, and calculate the degree to which known lifestyle and clinical factors predict RA-ILD.MethodsThis nested case-control study matched incident RA-ILD cases to RA non-ILD controls on age, sex, RA duration, rheumatoid factor, and time from exposure assessment to RA-ILD. Exposures included education, BMI, smoking, anticyclic citrullinated peptide antibodies, race, joint erosions, rheumatoid nodules, C-reactive protein (CRP), disease activity score, functional status, disease-modifying antirheumatic drug use, and glucocorticoid use. OR for each exposure on risk of RA-ILD were obtained from logistic regression models. Area under the curve (AUC) was calculated based on all lifestyle and clinical exposures.ResultsWe identified 84 incident RA-ILD cases and 233 matched controls. After adjustment, obesity, high-positive CRP (≥ 10 mg/L), and poor functional status (multidimensional Health Assessment Questionnaire [MDHAQ] ≥ 1) were associated with increased risk of RA-ILD (OR 2.42, 95% CI 1.11–5.24 vs normal BMI; OR 2.61, 95% CI 1.21–5.64 vs CRP < 3 mg/L; OR 3.10, 95% CI 1.32–7.26 vs MDHAQ < 0.2). Smoking 30 pack-years or more was strongly associated with risk of RA-ILD compared to never smokers (OR 6.06, 95% CI 2.72–13.5). Together, lifestyle and clinical risk factors for RA-ILD had an AUC of 0.79 (95% CI 0.73–0.85).ConclusionObesity, CRP, functional status, and extensive smoking may be novel risk factors for RA-ILD that may be useful for RA-ILD risk assessment and prevention. The overall ability to predict RA-ILD remains modest.

ObjectiveTo examine the efficacy and safety of pegloticase in combination with methotrexate (MTX) in patients with uncontrolled gout in an exploratory, open-label clinical trial (ClinicalTrials.gov: NCT03635957) prior to a randomized, controlled trial.MethodsA multicenter, open-label efficacy and safety study of pegloticase with MTX co-treatment was conducted in patients with uncontrolled gout. Patients were administered oral MTX (15 mg/week) and folic acid (1 mg/day) 4 weeks prior to and throughout pegloticase treatment. The primary study outcome was the proportion of responders, defined as serum uric acid (sUA) < 6 mg/dL for ≥ 80% of the time during Month 6 (Weeks 20, 22, and 24). All analyses were performed on a modified intent-to-treat population, defined as patients who received ≥ 1 pegloticase infusion.ResultsSeventeen patients were screened and 14 patients (all men, average age 49.3 ± 8.7 years) were enrolled. On Day 1, mean sUA was 9.2 ± 2.5 mg/dL, and 12 of the 14 patients had visible tophi. At the 6-month timepoint, 11/14 (78.6%, 95% CI 49.2–95.3%) met the responder definition, with 3 patients discontinuing after meeting protocol-defined treatment discontinuation rules (preinfusion sUA values > 6 mg/dL at 2 consecutive scheduled visits). All patients tolerated MTX. No new safety concerns were identified.ConclusionIn this study, an increased proportion of patients maintained therapeutic response at 6 months when treated concomitantly with MTX and pegloticase as compared to the previously reported 42% using pegloticase alone. These results support the need for a randomized study of MTX or placebo with pegloticase to validate these open-label findings.

SB4, SB2, and SB5 are biosimilars of etanercept (ETN), infliximab (INF), and adalimumab (ADA), respectively. This pooled analysis evaluated the immunogenicity of these treatments across three phase...

OBJECTIVE: To provide guidance to rheumatology providers on the management of adult rheumatic disease in the context of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A task force, including 10 rheumatologists and 4 infectious disease specialists from North America, was convened. Clinical questions were collated, and an evidence report was rapidly generated and disseminated. Questions and drafted statements were reviewed and assessed using a modified Delphi process. This included 2 rounds of asynchronous anonymous voting by e-mail and 3 webinars with the entire panel. Task force members voted on agreement with draft statements using a 1-9-point numerical scoring system, and consensus was determined to be low, moderate, or high based on the dispersion of votes. For approval, median votes were required to meet predefined levels of agreement (median values of 7-9, 4-6, and 1-3 defined as agreement, uncertainty, or disagreement, respectively) with either moderate or high levels of consensus. RESULTS: The task force approved 77 initial guidance statements: 36 with moderate and 41 with high consensus. These were combined, resulting in 25 final guidance statements. CONCLUSION: These guidance statements are provided to promote optimal care during the current pandemic. However, given the low level of available evidence and the rapidly evolving literature, this guidance is presented as a "living document," and future updates are anticipated.

Objective To provide guidance to rheumatology providers on the management of adult rheumatic disease in the context of the coronavirus disease 2019 (COVID-19) pandemic. Methods A task force, including 10 rheumatologists and 4 infectious disease specialists from North America, was convened. Clinical questions were collated, and an evidence report was rapidly generated and disseminated. Questions and drafted statements were reviewed and assessed using a modified Delphi process. This included asynchronous anonymous voting by email and webinars with the entire panel. Task force members voted on agreement with draft statements using a 1-9-point numerical scoring system, and consensus was determined to be low, moderate, or high based on the dispersion of votes. For approval, median votes were required to meet predefined levels of agreement (median values of 7-9, 4-6, and 1-3 defined as agreement, uncertainty, or disagreement, respectively) with either moderate or high levels of consensus. Results Draft guidance statements approved by the task force have been combined to form final guidance. Conclusion These guidance statements are provided to promote optimal care during the current pandemic. However, given the low level of available evidence and the rapidly evolving literature, this guidance is presented as a "living document," and future updates are anticipated.

INTRODUCTION: We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with abnormalities on pulmonary function tests (PFTs). METHODS: We studied RA serostatus and PFT abnormalities within a RA registry. RA serostatus was assessed by research assays for cyclic citrullinated peptide (CCP) and rheumatoid factor (RF). Outcomes were abnormalities on clinically-indicated PFTs, including restriction, obstruction, and diffusion abnormality. Logistic regression was used to obtain ORs and 95%CIs for the PFT abnormalities by RA serologic phenotypes independent of lifestyle and RA characteristics. RESULTS: Among 1,272 analyzed subjects, mean age was 56.3 years (SD 14.1), 82.2% were female, and 69.5% were seropositive. There were 100 subjects with abnormal PFTs. Compared to seronegativity, seropositivity was associated with increased odds of any PFT abnormality (multivariable OR 2.29, 95%CI 1.30-4.03). When analyzing type of PFT abnormality, seropositivity was also associated with restriction, obstruction, and diffusion abnormalities; multivariable ORs were 2.48 (95%CI 1.26-4.87), 3.12 (95%CI 1.28-7.61), and 2.30 (95%CI 1.09-4.83), respectively. When analyzing by CCP and RF status, the associations were stronger for RF+ than for CCP+ (any PFT abnormality: OR 1.99, 95%CI 1.21-3.27 for RF+ vs. RF−; OR 1.67, 95%CI 1.03-2.69 for CCP+ vs. CCP−) with a dose effect of higher RF titer increasing odds for each PFT abnormality (p for trend

ObjectivesTo detail the greatest areas of unmet scientific and clinical needs in rheumatology.MethodsThe 21st annual international Advances in Targeted Therapies meeting brought together more than 100 leading basic scientists and clinical researchers in rheumatology, immunology, epidemiology, molecular biology and other specialties. During the meeting, breakout sessions were convened, consisting of 5 disease-specific groups with 20–30 experts assigned to each group based on expertise. Specific groups included: rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematosus and other systemic autoimmune rheumatic diseases. In each group, experts were asked to identify unmet clinical and translational research needs in general and then to prioritise and detail the most important specific needs within each disease area.ResultsOverarching themes across all disease states included the need to innovate clinical trial design with emphasis on studying patients with refractory disease, the development of trials that take into account disease endotypes and patients with overlapping inflammatory diseases, the need to better understand the prevalence and incidence of inflammatory diseases in developing regions of the world and ultimately to develop therapies that can cure inflammatory autoimmune diseases.ConclusionsUnmet needs for new therapies and trial designs, particularly for those with treatment refractory disease, remain a top priority in rheumatology.

Objective To develop and evaluate an adjusted score for the multi-biomarker disease activity (MBDA) test to account for the effects of age, sex and adiposity in patients with RA. Methods Two models were developed to adjust MBDA score for age, sex and adiposity, using either serum leptin concentration or BMI as proxies for adiposity. Two cohorts were studied. A cohort of 325 781 RA patients who had undergone commercial MBDA testing and had data for age, sex and serum leptin concentration was used for both models. A cohort of 1411 patients from five studies/registries with BMI data was used only for the BMI-adjusted MBDA score. Univariate and multivariate linear regression analyses evaluated the adjusted MBDA scores and conventional clinical measures as predictors of radiographic progression, assessed in terms of modified total Sharp score (ΔmTSS). Results Two models were developed, based on findings that MBDA score was higher in females than males and increased with age, leptin concentration and BMI. In pairwise regression analyses, the leptin-adjusted (P = 0.00066) and BMI-adjusted (P = 0.0027) MBDA scores were significant independent predictors of ΔmTSS after adjusting for DAS28-CRP, whereas DAS28-CRP was not, after adjusting for leptin-adjusted (P = 0.74) or BMI-adjusted (P = 0.87) MBDA score. Moreover, the leptin-adjusted MBDA score was a significant predictor of ΔmTSS after adjusting for the BMI-adjusted MBDA score (P = 0.025) or the original MBDA score (0.027), whereas the opposite was not true. Conclusion Leptin-adjusted MBDA score significantly adds information to DAS28-CRP and the original MBDA score in predicting radiographic progression. It may offer improved clinical utility for personalized management of RA.

OBJECTIVE To investigate the safety and efficacy of ABT-122, a tumor necrosis factor (TNF)- and interleukin-17A (IL-17A)-targeted dual variable domain immunoglobulin, in patients with active psoriatic arthritis (PsA) who have experienced an inadequate response to methotrexate. METHODS Patients (n = 240) were randomized to receive ABT-122 (120 or 240 mg every week), adalimumab (40 mg every other week), or placebo in a 12-week double-blind, parallel-group study. The primary efficacy end point was the proportion of patients achieving ≥20% improvement in disease activity according to the American College of Rheumatology response criteria (ACR20) at week 12. Secondary and exploratory 12-week end points included 50% improvement (ACR50) and 70% improvement (ACR70) response rates, and proportion of patients meeting the Psoriasis Area and Severity Index (PASI) response criteria for ≥75% (PASI75) and ≥90% (PASI90) improvement in skin scores among those with ≥3% of their body surface area affected by psoriasis. RESULTS In both ABT-122 dose groups, ACR20 response rates at week 12 (64.8-75.3%) were superior to that in patients receiving placebo (25.0%) (P < 0.001) but similar to that in patients receiving adalimumab (68.1%). ACR50 and ACR70 response rates were also superior in both ABT-122 dose groups (36.6-53.4% and 22.5-31.5%, respectively) compared to the placebo group (12.5% and 4.2%, respectively) (P < 0.05). Among eligible patients in the placebo, adalimumab, ABT-122 120 mg every week, and ABT-122 240 mg every week treatment groups, PASI75 responses were achieved in 27.3%, 57.6%, 74.4%, and 77.6% of patients, respectively, whereas PASI90 responses were achieved in 18.2%, 45.5%, 48.8%, and 46.9% of patients, respectively. Frequencies of treatment-emergent adverse events, including infections, were similar across all treatment groups, causing no discontinuations. No serious infections or systemic hypersensitivity reactions were reported with ABT-122. CONCLUSION Dual neutralization of TNF and IL-17A with ABT-122 had efficacy and safety that was similar to, and not broadly differentiated from, that of adalimumab over a 12-week treatment course in patients with PsA.

Objectives: Describe the development and feasibility of a telephone peer support program that provides education, emotional support, and enhances coping skills among rheumatoid arthritis (RA) patients. Methods: In an academic arthritis center, peer coaches received 5 training modules: 1) definition and expectations of peer coaching, 2) structure/management of phone calls, 3) confidentiality, 4) psychological techniques for encounters, 5) referral guidelines and resources. Follow-up, acceptability and comparison with patients receiving standard care included mean adjusted change differences at 6 months in fatigue, pain, self-efficacy, functional status (SF-12), flare frequency and medication adherence (ASK-20). Results: Eighteen peer coaches were assigned on average, 1.7 (SD, 1.4) patients. They spoke 8.4 (SD, 7.2) times; 21 of 29 patients completed the program. The most common topics requested were how to manage flares, 10(48%), medical aspects of RA, 10(48%) and understanding how to live with RA, 9(43%). After 6 months, non-significant improvements occurred in study outcomes (largest changes SF-12 PCS (mean adjusted change (SE) intervention v. standard care, 4.7(2.6) v. 0.5(2.0)) and how RA impacts one’s life (1.8(6.4) v. −4.9(5.8)). Participants reported many benefits from peer support. They felt less alone, 13(62%), more part of a sharing community, 12(57%) and had a better understanding of RA, 9(43%). They felt calmer, 9(43%), less sad,5(24%) and that they had more support from family and friends, 5(24%). Conclusions: An RA telephone peer support program is feasible and acceptable to patients. While the study was underpowered to detect statistical improvements, patients reported benefits suggesting the need for randomized evaluation.

OBJECTIVE Current validated cardiovascular (CV) risk estimates were developed in populations with relatively stable levels of inflammation, whereas patients with rheumatoid arthritis (RA) routinely experience significant changes in inflammation. This study was undertaken to test whether changes in inflammation affect estimated CV risk as measured using validated population-based risk calculators. METHODS Participants in a prospective RA cohort who experienced a decrease or an increase of ≥10 mg/liter in the C-reactive protein (CRP) level at 2 consecutive time points 1 year apart (CRP decrease group and CRP increase group, respectively) were included in this study. We estimated 10-year CV risk using the following calculators: Framingham Risk Score, 2013 American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Score, Reynolds Risk Score (RRS), and QRISK2. Of these calculators, only the RRS includes a variable addressing the CRP level. Paired t-tests were performed to compare risk scores at baseline and 1-year follow-up. We calculated the correlations between the changes in risk scores and changes in pro-B-type natriuretic peptide (pro BNP), a surrogate marker of CV risk. RESULTS One hundred eighty RA patients were included in the study (mean age 57.8 years, 84% female, 80% seropositive). Of the calculators studied, only the RRS was sensitive to changes in inflammation; an increase in inflammation was associated with increased estimated CV risk (P < 0.0001), and only the RRS was correlated with changes in proBNP (r = 0.17, P = 0.03). CONCLUSION Our data showed no significant change in CV risk estimated using validated general population CV risk calculators except for the RRS. These findings suggest that CV risk may be modulated by changes in inflammation in RA, which is not typically considered when using existing CV risk calculators.

Objective The 24-week equivalent efficacy and comparable safety results of the biosimilar SB5 and reference adalimumab (ADA) from the phase III randomized study in patients with moderate-to-severe rheumatoid arthritis (RA) have been reported previously. We undertook this transition study to evaluate patients who switched from ADA to SB5 or who continued to receive SB5 or ADA up to 52 weeks. Methods In this phase III study, patients were initially randomized 1:1 to receive SB5 or ADA (40 mg subcutaneously every other week). At 24 weeks, patients receiving ADA were rerandomized 1:1 to continue with ADA (ADA/ADA group) or to switch to SB5 (ADA/SB5 group) up to week 52; patients receiving SB5 continued with SB5 for 52 weeks (SB5 group). Efficacy, safety, and immunogenicity were evaluated up to 52 weeks. Results The full analysis set population consisted of 542 patients (269 in the SB5 group, 273 in the ADA overall group [patients who were randomized to receive ADA at week 0], 125 in the ADA/SB5 group, and 129 in the ADA/ADA group). The percentages of patients meeting the American College of Rheumatology 20%, 50%, or 70% improvement criteria (achieving an ACR20, ACR50, or ACR70 response) at week 24 were maintained after the transition from ADA to SB5, and these response rates were comparable across treatment groups throughout the study. ACR20 response rates ranged from 73.4% to 78.8% at week 52. Radiographic progression was minimal and comparable across treatment groups. The safety profile and the incidence of antidrug antibodies were comparable across treatment groups after transition. Conclusion SB5 was well tolerated over 1 year in patients with RA, with efficacy, safety, and immunogenicity comparable to those of ADA. Switching from ADA to SB5 had no treatment-emergent issues such as increased adverse events, increased immunogenicity, or loss of efficacy.

Introduction To assess the relationship between low bone mineral density (BMD), anti-cyclic citrullinated peptide-2 (anti-CCP2) antibodies, and disease activity in patients with established rheumatoid arthritis (RA). Methods Patients enrolled in a single-center, observational cohort registry of patients with RA. Eligible patients had known BMD, as measured by digital X-ray radiogrammetry (DXR–BMD), and anti-CCP2 antibody measurements at the same time point or within 6 months. Anti-CCP2–immunoglobulin (Ig)G-positive (+) patients (≥ 20 U/mL) were distributed into three equal groups (Gp1–3), representing increasing anti-CCP2 antibody concentrations. Associations between BMD and anti-CCP2 antibody status and titer were explored in multivariate regression analyses controlling for covariates (including age, duration of RA, use of steroids, use of osteoporosis medication). Association between disease activity (DAS28 [CRP] Results A total of 149 patients (all women) were included (47 anti-CCP2 antibody negative [−], 102 anti-CCP2+ [34\titer group]). Mean disease duration was greater in the three anti-CCP2+ groups vs. the anti-CCP2− group. DXR–BMD was lower in the anti-CCP2+ vs. the anti-CCP2− groups (Gp1–3 vs. anti-CCP2−: P P P = 0.0181). Conclusion Among patients with established RA, data suggest that anti-CCP2+ patients, particularly those with high anti-CCP2 antibody titers, have lower hand BMD, and patients with lower hand BMD are less likely to have low disease activity. Funding Bristol-Myers Squibb. Trial Registration Clinicaltrials.gov identifier, NCT01793103.

The 19th annual international Targeted Therapies meeting brought together over 100 leading basic scientists and clinical researchers from around the world in the field of immunology, molecular biology and rheumatology and other specialties. During the meeting, breakout sessions were held consisting of 5 disease-specific groups with 20-40 experts assigned to each group based on clinical or scientific expertise. Specific groups included: rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematous, connective tissue diseases (e.g. Sjogren's syndrome, Systemic sclerosis, vasculitis including Bechet's and IgG4 related disease), and a basic science immunology group spanning all of the above clinical domains. In each group, experts were asked to consider and update previously identified unmet needs in 3 categorical areas: basic/translational science, clinical science and therapeutic development, and clinical care. Overall, similar primary unmet needs were identified within each disease foci, and several additional needs were identified since the time of last year's congress. Within translational/basic science, the need for better understanding the heterogeneity within each disease was highlighted so that predictive tools for therapeutic responses can be developed. Within clinical science and therapeutic trials, a strong focus was placed upon the need to identify pre-clinical states of disease allowing prevention in those at risk. The ability to cure remains perhaps the ultimate unmet need. Further, the need to develop new and affordable therapeutics, as well as to conduct strategic trials of currently approved therapies was again highlighted. Within the clinical care realm, improved co-morbidity management and patient-centered care were identified as unmet needs. Lastly, it was strongly felt there was a need to develop a scientific infrastructure for well-characterized, longitudinal cohorts paired with biobanks and mechanisms to support data-sharing. This infrastructure could facilitate many of the unmet needs identified within each disease area.

Background:Busy rheumatologists may assess disease activity and risk for radiographic progression (RP) in RA with informal, qualitative versions of evaluator and/or patient global assessments (EGA and PGA). RA patient care may be improved by having a convenient, objective disease activity measure that predicts risk for RP more accurately than EGA or PGA.Objectives:To compare the abilities of MBDA score, patient global assessment and evaluator global assessment to assess risk for radiographic progression (RP), and to assess the ability of MBDA score to predict RP among patients with concordant or discordant PGA and EGA.Methods:Patients were pooled from two RCTs of patients with recent onset RA treated with conventional and biologic DMARDs (OPERA and SWEFOT, N=386) and from a registry of patients with predominantly established RA and diverse treatments (BRASS, N=380). Pearson correlations were determined between MBDA scores (adjusted for the effects of age, sex and adiposity) (scale 1-100), PGA and EGA (each on a scale of 1-10) at baseline. PGA and EGA were considered discordant when they differed by >2.5. Univariable logistic regression assessed ability to predict RP (change in TSS >5 over 1 year) for MBDA score, PGA and EGA as continuous variables; and for discordance of PGA and EGA as 2-level (concordant vs. discordant) or 3-level (PGA>EGA, concordant, EGA>PGA) categorical variables. Multivariable regression considered the main effect and interaction terms of the MBDA score, as a continuous variable, paired with each other variable, to test the ability of each pair to assess risk of RP. All models included a random effect on cohort. Odds ratios were reported for every 10-unit increase in MBDA score. Frequency of RP was determined in subgroups with MBDA score low (44) for patient groups based on PGA/EGA concordance or discordance.Results:The 766 patients studied were 76% female, 76% positive for RF and/or anti-CCP Ab, with mean age 55 years, DAS28-CRP 4.7, CRP 22 mg/L, CDAI 26, SJC 9.1, PGA 4.4, EGA 3.4, MBDA score 53. No interaction was seen between MBDA score and type of cohort (early vs established RA). PGA and EGA were discordant in 294 of 766 (38%) patients and were weakly to moderately correlated (r=0.38). Among discordant patients, PGA was >EGA in 227 cases and EGA was >PGA in 67 cases. Correlations between MBDA score and PGA or EGA were r=0.41 and r=0.34, respectively. In univariable analyses, MBDA score was a statistically significant predictor of radiographic progression (OR=1.53, p=6.3x10-8) whereas PGA, EGA, 2-level discordance and 3-level discordance were not (p=0.38, 0.47, 0.74, 0.83, respectively). In multivariable analyses, significant interactions were observed between MBDA score and discordance (2-level, p=0.0029; 3-level, p=0.0087). The interaction analysis demonstrated, in PGA/EGA-concordant patients, low risk of radiographic progression when MBDA score was low and elevated risk when it was high (OR=1.33 [1.1, 1.59]). A relationship between MBDA score and RP risk was also demonstrated, with heightened trend, among discordant patients with PGA >EGA (OR=2.04 [1.53, 2.81]) and EGA >PGA (OR=3.43 [1.37, 13.8]) (Figure 1).Conclusion:MBDA score was a significant predictor of radiographic progression, whereas PGA and EGA were not. MBDA score predicted progression whether PGA and EGA were concordant or discordant. These results suggest that MBDA score detects joint-damaging disease activity more accurately than PGA and EGA and it does so whether or not PGA and EGA are in agreement.Disclosure of Interests:Leonard Calabrese Grant/research support from: AbbVie, Bristol-Myers Squibb, Cresecendo, Genentech, Gilead, GlaxoSmithKline, Horizon, Janssen, Novartis, and Sanofi., Michael E. Weinblatt Shareholder of: Canfite, Inmedix, Scipher, and Vorso, Consultant of: AbbVie, Aclaris, Amgen, Bayer, Bristol-Myers Squibb, Crescendo Bioscience, Corrona, EqRX, GSK,Genosco, Gilead, Lilly, Novartis, Pfizer, Roche, Set Point, Grant/research support from: Bristol-Myers Squibb, Myriad Genetics, Inc.,Eli Lilly and Sanofi, Nancy Shadick Consultant of: BMS, Grant/research support from: Lilly, mallinckrodt, BMS, Amgen and Sanofi, Cecilie Heegaard Brahe: None declared, Mikkel Østergaard Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Novartis, Orion, Pfizer, Regeneron, Roche, Takeda, and UCB, Grant/research support from: AbbVie, BMS, Celgene, Myriad Genetics, Inc., Janssen, and Merck, Merete L. Hetland Speakers bureau: Orion, Grant/research support from: AbbVie, Biogen, BMS, CelltrionRoche, Myriad Genetics, Inc., Eli Lily, MSD, Pfizer, and UCB, Megan Horton Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Darl Flake Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Eric Sasso Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Autoimmune

Objective Patients with rheumatoid arthritis (RA) often ask whether specific foods, popularized as inflammatory or antiinflammatory, can improve or worsen their RA. Patients with RA took a survey on diet and RA symptoms, and the survey data were collected and analyzed. Methods A dietary survey was mailed to 300 subjects in a single-center RA registry at a large academic center. Subjects were asked about their consumption of 20 foods and whether these foods make their RA symptoms better, worse, or unchanged. Semiannual registry data include demographics, medications, comorbidities, and disease activity scores. Fisher's exact test and Wilcoxon's rank sum tests evaluated associations between subject characteristics from the most recent registry assessment and changes in RA symptoms from specific foods. Results Of the 217 subjects (72% response rate), 83% were female; the median RA duration was 17 years (interquartile range 9–27 years), and 58% were taking a biologic disease-modifying antirheumatic drug. Twenty-four percent of subjects reported that foods affect their RA symptoms, with 15% reporting improvement and 19% reporting worsening. Blueberries and spinach were the foods most often reported to improve RA symptoms, while soda with sugar and desserts were those most often reported to worsen RA symptoms. Younger age and noting that sleep, warm room temperature, and vitamin/mineral supplements improve RA were each associated with reporting that foods affect RA symptoms. Medication use, sex, body mass index, smoking, disease duration, disease activity scores, and self-reported RA flares were not associated with reporting that foods affect RA. Conclusion Nearly one-quarter of RA subjects with longstanding disease reported that diet had an effect on their RA symptoms.

Objective SB5 is a biosimilar agent for adalimumab (ADA). The aim of this study was to evaluate the efficacy, pharmacokinetics (PK), safety, and immunogenicity of SB5 in comparison with reference ADA in patients with rheumatoid arthritis (RA). Methods In this phase III, randomized, double-blind, parallel-group study, patients with moderately to severely active RA despite treatment with methotrexate were randomized 1:1 to receive SB5 or reference ADA at a dosage of 40 mg subcutaneously every other week. The primary efficacy end point was the response rate based on the American College of Rheumatology 20% improvement criteria (ACR20) at week 24 in the per-protocol set (completer analysis). Additional end points included efficacy, PK, safety, and immunogenicity assessments. Results Of the 544 patients randomized to receive a study drug, the full analysis set comprised 542 patients (269 in the SB5 group, 273 in the reference ADA group) and the per-protocol set comprised 476 patients (239 receiving SB5, 237 receiving reference ADA). The ACR20 response rate at week 24 in the per-protocol set was equivalent between those receiving SB5 and those receiving reference ADA (72.4% and 72.2%, respectively); the difference in the ACR20 response rate (0.1%, [95% confidence interval −7.83%, 8.13%]) was within the predefined equivalence margin (±15%). Similar results were seen in the full analysis set (missing data being considered a nonresponse). The SB5 and reference ADA treatment groups were comparable across other end points, including the ACR 50% and ACR 70% improvement response rates, Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate, PK data, incidence of treatment-emergent adverse events, and the antidrug antibody response. Subgroup analyses showed that the efficacy and safety of SB5 and reference ADA were comparable regardless of antidrug antibody status. Conclusion The ACR20 response rate at week 24 was equivalent between patients treated with the biosimilar agent SB5 and those treated with reference ADA. SB5 and reference ADA were both well tolerated, with comparable safety profiles, in patients with RA.

Objective Previous cross-sectional studies have shown that rheumatoid arthritis (RA) patients with fibromyalgia (FM) have higher disease activity, greater medical costs, and worse quality of life compared to RA patients without FM. We determined the impact of FM on 2-year changes in the functional status of RA patients in a prospective study. Methods Subjects included participants in the Brigham Rheumatoid Arthritis Sequential Study who were enrolled in a substudy of the effects of pain in RA. Subjects completed questionnaires, including the Multi-Dimensional Health Assessment Questionnaire (MDHAQ) and Polysymptomatic Distress (PSD) scale, semiannually, and underwent physical examination and laboratory tests yearly. Results Of the 156 included RA subjects, 16.7% had FM, while 83.3% did not. In a multivariable linear regression model adjusted for age, sex, race, baseline MDHAQ score, disease duration, rheumatoid factor/cyclic citrullinated peptide antibody seropositivity, disease activity, and psychological distress, RA patients with FM had a 0.14 greater 2-year increase in MDHAQ score than RA patients without FM (P = 0.021). In secondary analyses examining the association between continuous PSD scale score and change in MDHAQ, higher PSD scale scores were significantly associated with greater 2-year increases in MDHAQ score (β coefficient 0.013, P = 0.011). Conclusion Both the presence of FM and increasing number of FM symptoms predicted worsening of functional status among individuals with RA. Among individuals with RA and FM, the magnitude of the difference in changes in MDHAQ was 4- to 7-fold higher than typical changes in MDHAQ score among individuals with established RA.

Objective: In disease-modifying antirheumatic drug–naive patients with early rheumatoid arthritis (RA) who had achieved sustained low disease activity (a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate of ≤3.2 at both week 40 and week 52) after 1 year of treatment with certolizumab pegol (CZP) at a standard dose (200 mg every 2 weeks plus optimized methotrexate [MTX]), we evaluated whether continuation of CZP treatment at a standard dose or at a reduced frequency (200 mg every 4 weeks plus MTX) was superior to stopping CZP (placebo plus MTX) in maintaining low disease activity for 1 additional year. Methods: A total of 293 patients from period 1 of our study were re-randomized 2:3:2 in period 2 to CZP at a standard dose (n = 84), CZP at a reduced frequency (n = 127), or placebo plus MTX (CZP stopped) (n = 82). The primary end point was the percentage of patients who maintained low disease activity throughout weeks 52–104 without flares. We used a hierarchical testing scheme, comparing CZP at a standard dose with CZP stopped. If P < 0.05 was achieved, then CZP at a reduced frequency was compared with CZP stopped (nonresponder imputation). Results: The 293 patients from period 1 represented 36% fewer patients than projected, yielding a smaller number of patients eligible for period 2. Higher proportions of patients treated with the standard and reduced frequency regimens maintained low disease activity than those who had stopped CZP (48.8% and 53.2%, respectively, versus 39.2% [P = 0.112 and P = 0.041, respectively; nominal P value, first hierarchical test not significant]). Similar trends were observed for radiographic nonprogression (change from baseline of ≤0.5 in modified Sharp/van der Heijde score; 79.2% and 77.9% of patients, respectively, versus 70.3%) and normative physical function (Health Assessment Questionnaire disability index score of ≤0.5; 71.4% and 70.6% of patients, respectively, versus 57.0%). Safety profiles were similar between all groups, with no new safety signals identified for continuing CZP to week 104. No deaths were reported. Conclusion: The study failed to meet its primary end point. However, there were no clinically meaningful differences between the standard and reduced frequency doses of CZP plus MTX; both controlled RA more effectively than stopping CZP.

Objective: To characterize physical activity (PA) participation (meeting ≥150-minutes of moderate intensity or 75-minutes of vigorous (MVPA/week)), examine associations between disease activity and MVPA and identify MVPA correlates in adults with rheumatoid arthritis (RA) over 3 years. Methods: This study included 573 RA patients (94% Caucasian, 83% female, mean age 61 years, mean RA duration 19.5 years) with ≥1 annual registry visit and who completed the PA questionnaire. Baseline and annual measures included: demographics/medical history, self-efficacy for disease management, quality of life, patient/physician global assessment, physical function, and self-reported PA. A logistic repeated measures model using the Generalized Estimation Equation examined the relationship between disease activity and MVPA. Results: Average disease activity (DAS28-CRP3) was 3.1 (SD, 1.4), 36% were physically inactive and 29% met MVPA recommendations. There was a negative borderline association with disease activity (OR=0.89; 95%CI 0.79–1.00). Correlates of meeting MVPA recommendations, adjusting for disease activity, were being Caucasian (OR=2.95; 95%CI 1.29–6.75), older age (age >69 OR=0.58; 95%CI 0.36–0.92) poor mental health (OR=0.63; 95%CI 0.41–0.95), poor physical function (OR=0.59; 95%CI 0.34–1.01), overweight/obese (body mass index >25–30 OR=0.69; 95%CI 0.50–0.95; >30–39.9 OR=0.60; 95%CI 0.41–0.88; ≤40 OR=0.24; 95%CI 0.08–0.74) and patient global assessment (≥10-20) OR=0.57; 95%CI 0.39–0.83). Conclusions: A small proportion met MVPA recommendations despite well-controlled disease. Disease activity was negatively associated with PA over time. PA correlates were linked to lifestyle, mental health and patient perceptions of disease, suggesting PA interventions that address patient perspectives may facilitate RA management. This article is protected by copyright. All rights reserved.

BackgroundTo assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with active rheumatoid arthritis and an inadequate response to methotrexate (MTX).MethodsIn this double-blind phase 3 study, patients were randomised 3:3:2 to placebo (n=488), baricitinib 4 mg once daily (n=487), or adalimumab 40 mg biweekly (n=330) with background MTX. PROs included the SF-36, EuroQol 5-D (EQ-5D) index scores and visual analogue scale, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient’s Global Assessment of Disease Activity (PtGA), patient’s assessment of pain and Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis (WPAI-RA), and measures collected in electronic patient daily diaries: duration and severity of morning joint stiffness (MJS), Worst Ttiredness and Worst Joint Pain. The primary study endpoint was at week 12. Treatment comparisons were assessed with logistic regression for categorical measures or analysis of covariance for continuous variables.ResultsCompared with placebo and adalimumab, baricitinib showed statistically significant improvements (p≤0.05) in HAQ-DI, PtGA, pain, FACIT-F, SF-36 physical component score, EQ-5D index scores and WPAI-RA daily activity at week 12. Improvements were maintained for measures assessed to week 52. Statistically significant improvement in patient diary measures (MJS duration and severity), worst tiredness and worst joint pain were observed for baricitinib versus placebo and adalimumab at week 12 (p≤0.05).ConclusionsBaricitinib provided significantly greater improvement in most PROs compared with placebo and adalimumab, including physical function MJS, pain, fatigue and quality of life. Improvement was maintained to the end of the study (week 52).Trial registrationNCT01710358.

Objective To quantify differences and determine the factors contributing to the difference in patient global assessment of rheumatoid arthritis (RA) disease activity (PtGA) between RA patients with multiple morbidities (RA-MM) and those with RA only. Methods We compared the PtGA between RA-MM patients and those with RA only, followed up in a longitudinal cohort (n = 1,040). In analyses performed on RA-MM patients (n = 575) and those with RA only (matched for swollen joint count, tender joint count, evaluator global assessment, and disease duration), the mean difference in PtGA (ΔPtGA) between the 2 groups was assessed. The contribution of patient characteristics to the explained variation of ΔPtGA in the matched cohort was calculated as semipartial R2 and summarized as the percentage of the total R2 in linear regression models. Results RA-MM patients reported higher (or worse) PtGA, with an increased PtGA associated with more morbidities (P for linear trend