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Objective: The gastrointestinal tract (GIT) is the most commonly affected internal organ in systemic sclerosis (SSc). We sought to determine the prevalence and impact of GIT symptoms on survival and patient-reported outcomes., Methods: A total of 907 consecutive patients from the Australian Scleroderma Cohort Study who had prospectively completed the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 Questionnaire (UCLA GIT) between 2015 and 2021 were included. The associations between UCLA GIT scores and physical function (Scleroderma Health Assessment Questionnaire), quality of life (QoL; Short Form 36), mood (Patient-Reported Outcomes Measurement Information System [PROMIS] anxiety and depression domains), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue score), and employment were investigated using multivariable population-averaged panel models using generalized estimating equations (GEEs). Kaplan-Meier curves and multivariable Cox proportional hazard regression models were used to evaluate survival according to total UCLA GIT scores., Results: GIT symptoms were reported in 87% of participants, with 46% to 52% reporting moderate to very severe symptoms of reflux, distension, diarrhea, and constipation. Higher total UCLA GIT scores were associated with worse QoL, physical function, fatigue, anxiety, and depression (P < 0.001). In the multivariable GEE analysis, moderate and severe to very severe total scores, reflux scores, and distension scores were associated with worse physical function, QoL, fatigue, anxiety, and depression compared to mild scores (P < 0.05). Patients with severe total scores and diarrhea scores were more likely to be unemployed compared to those with mild scores (P < 0.05). UCLA GIT total scores were not independently associated with death in our cohort., Conclusion: GIT manifestations are common in SSc and negatively impact QoL, physical function, and employment but are not directly associated with increased death., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Methotrexate (MTX) is effective in controlling disease activity in rheumatoid arthritis (RA). Parenteral MTX may have benefits over oral MTX, but it is rarely used in practice. To better understand this low usage rate, it is necessary to explore the barriers and enablers of therapy from the perspective of RA patients. The objectives of this scoping review were to describe RA patients' perspectives on the barriers and enablers in the use of parenteral MTX and to identify the research gaps in this field., Methods: The search was performed in Medline, Embase, Scopus, and Cochrane Library from inception to May 2021. Data synthesis was conducted using the Theoretical Framework of Acceptability. This scoping review included any type of study that explored the use of parenteral MTX by adult RA patients from the patients' perspective, written in English., Results: Fifteen studies were included; findings related to the constructs "affective attitude," "burden," "intervention coherence," and "self-efficacy" were explored the most, while some were rarely ("opportunity cost" and "perceived effectiveness") or not ("ethicality") reported. RA patients were generally satisfied with MTX injections ("affective attitude"). From the burden construct, the requirement for dexterity for administering MTX by injection was considered a barrier, whereas the lack of significant pain from MTX injection was considered an enabler., Conclusion: The findings suggested that patients generally preferred parenteral MTX formulations with attributes that facilitate self-administration. However, much of the identified research focused on prefilled pen devices, and significant gaps were identified, such as a lack of qualitative research., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Leflunomide is a commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). Its effects are mediated via inhibition of dihydroorotate dehydrogenase (DHODH) by its active metabolite teriflunomide, and the pharmacokinetics of teriflunomide are highly variable. Our objective was to examine the association between the DHODH haplotype and plasma teriflunomide concentration with response to leflunomide in patients with RA where leflunomide was added to an existing disease-modifying drug regimen after failure to achieve an adequate response with conventional triple therapy., Methods: Patients with RA who were taking, or were about to initiate, leflunomide were included. Participant characteristics, including the DHODH haplotype, were determined. Up to 5 plasma samples were collected after leflunomide was initiated for assays of total and free teriflunomide concentration. Disease activity was determined via the 28-joint Disease Activity Score (DAS28). The association between DAS28 scores and patient covariates was determined by linear mixed-effects modeling., Results: A total of 67 patients were included in the study. The DAS28 score after initiation of leflunomide was associated with the baseline DAS28 score (β = 0.70, P < 0.001) and was higher in those who carried the DHODH haplotype 2 (β = 0.56. P = 0.01) and did not carry the shared epitope (β = 0.56, P = 0.013). As total and free plasma teriflunomide concentration increased, the DAS28 score was significantly lower (P < 0.001 and P = 0.001, respectively). When considering threshold concentrations, teriflunomide concentrations >16 mg/liter were associated with a DAS28 score that was 0.33 lower, and when free teriflunomide concentration was >35 µg/liter, the DAS28 score was 0.32 lower., Conclusion: Teriflunomide concentration and carriage of the DHODH haplotype 2 are associated with response to leflunomide in patients with RA, and a total plasma teriflunomide concentration of at least 16 mg/liter is needed to maximize the likelihood of response., (© 2020, American College of Rheumatology.)

Objective: To determine whether foot synovitis is associated with adverse radiographic and functional outcomes after 3 years in an inception rheumatoid arthritis (RA) cohort receiving treat-to-target combination disease-modifying antirheumatic drug therapy., Methods: Disease activity was assessed in early RA patients (n = 266) using the Disease Activity Score in 28 joints, Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Radiographic outcomes were assessed with annual hand and feet radiographs and quality of life with the Short Form 36 (SF-36). The prevalence of remission and foot synovitis was calculated using marginal binomial generalized estimating equations, transition between remission and nonremission states by a multistate Markov model, and changes in radiographic scores by a negative binomial mixed regression log-link model. Population-matched SF-36 data were analyzed by mixed-effects linear regression., Results: Disease activity scores that omit foot joints were modest in their ability to capture foot synovitis. Despite the relative stringency of the SDAI and CDAI for remission, 25-36% of patients in remission had foot synovitis. In patients in remission, foot synovitis predicted transition from remission into relapse by up to 2-fold. The sustainability of remission markedly influenced the progression of erosion scores (P = 0.006). After adjusting for disease activity, foot synovitis was associated with worse SF-36 physical functioning scores (P = 0.025)., Conclusion: Disease activity measures that omit foot joints capture foot synovitis poorly. When it is used to define remission, foot synovitis is found in a substantial proportion of patients, which predicts relapse and worse physical function. Foot synovitis influences the sustainability of remission, which in turn markedly influences radiographic progression. Regardless of remission status, persistent foot synovitis should prompt therapy escalation in order to improve long-term outcomes., (© 2016, American College of Rheumatology.)

Objective: Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs)., Methods: We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc. Forty scleroderma experts rated 20 patient profiles each and assessed whether each patient had improved or not improved over a period of 1 year. Using the profiles for which raters had reached a consensus on whether the patients were improved versus not improved (79% of the profiles examined), we fit logistic regression models in which the binary outcome referred to whether the patient was improved or not, and the changes in the core set items from baseline to followup were entered as covariates. We tested the final index in a previously completed RCT., Results: Sixteen of 31 core items were included in the patient profiles after a consensus meeting and review of test characteristics of patient-level data. In the logistic regression model in which the included core set items were change over 1 year in the modified Rodnan skin thickness score, the forced vital capacity, the patient and physician global assessments, and the Health Assessment Questionnaire disability index, sensitivity was 0.982 (95% confidence interval 0.982-0.983) and specificity was 0.931 (95% confidence interval 0.930-0.932), and the model with these 5 items had the highest face validity. Subjects with a significant worsening of renal or cardiopulmonary involvement were classified as not improved, regardless of improvements in other core items. With use of the index, the effect of methotrexate could be differentiated from the effect of placebo in a 1-year RCT (P = 0.02)., Conclusion: We have developed a CRISS that is appropriate for use as an outcome assessment in RCTs of early dcSSc., (© 2016, American College of Rheumatology.)

Objective: Despite better disease suppression with combination disease-modifying antirheumatic drugs (DMARDs), some patients with rheumatoid arthritis (RA) have progressive erosive disease. The objective of this study was to determine whether hand bone mineral density (BMD) loss in the first 6 months of treatment indicates increased risk of erosions at 12 months., Methods: Patients with DMARD-naive early RA receiving treat-to-target therapy were studied (n = 106). Hand BMD was measured at baseline and 6 months by dual x-ray absorptiometry. Hand and feet radiographs were performed at baseline and 12 months and scored using the van der Heijde modification of the Sharp method. A K-means clustering algorithm was used to divide patients into 2 groups: the BMD loss group or the no loss group, according to their absolute change in BMD from baseline to 6 months. Multiple regression analysis (hurdle model) was performed to determine the risk factors for both erosive disease and erosion scores., Results: Hand BMD loss at 6 months was associated with erosion scores at 12 months (P = 0.021). In a multiple regression analysis, hand BMD loss (P = 0.046) and older age at onset (≥50 years; P = 0.014) were associated with erosive disease, whereas baseline erosion scores (P = 0.001) and anti-cyclic citrullinated peptide (P = 0.024) were correlated with erosion severity/progression., Conclusion: In RA patients receiving treat-to-target therapy, early hand BMD loss could identify patients who are at risk of developing erosive disease at 12 months, potentially allowing intensification of treatment to prevent erosive damage., (Copyright © 2014 by the American College of Rheumatology.)