28-joint Disease Activity Score Research Articles

Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA).

The optimal dose of rituximab in combination with leflunomide in patients with rheumatoid arthritis (RA) is not known. In Part 1 (previously reported) of the investigator-initiated AMARA study (EudraCT 2009-015950-39; ClinicalTrials.gov NCT01244958), improvements at week (W)24 were observed in patients randomized to rituximab + leflunomide compared with placebo + leflunomide. In the study reported here (Part 2), Part 1 responders received rituximab 500 or 1000 mg at W24/26 plus ongoing leflunomide. Patients were randomized at baseline to their eventual W24 treatment group. The Part 2 primary outcome was the mean Disease Activity Score-28 joints (DAS28) at W52, based on the last observation carried forward (LOCF) analyses and a two-sided analysis of variance. Patient-reported outcomes (PROs) and adverse events were evaluated. Eighty-three patients received rituximab at W24/26 (31 rituximab→rituximab 1000 mg; 29 rituximab→rituximab 500 mg; 10 placebo→rituximab 1000 mg; 13 placebo→rituximab 500 mg). At W52, there were no significant differences in DAS28 between rituximab doses in patients originally treated with rituximab or those originally treated with placebo. In the Part 1 placebo group, the higher rituximab dose was associated with greater improvements in ACR response rates and some PROs. Adverse events were similar regardless of rituximab dose. Retreatment with rituximab 500 mg and 1000 mg showed comparable efficacy, whereas an initial dose of rituximab 500 mg was associated with lower response rates versus 1000 mg. Reduced treatment response with the lower dose in patients initially treated with placebo may have been influenced by small numbers and baseline disease activity.

Clinical significance of Galectin-1 and Galectin-4 in rheumatoid arthritis patients and their potential role as diagnostic markers

Aim of the workTo investigate the utility of serum Galectin-1 (Gal-1) and Galectin-4 (Gal-4) as potential markers for diagnosis of rheumatoid arthritis (RA) and to explore their relationship with disease activity. Patients and methodsSerum Gal-1 and Gal-4 of 60 RA patients were compared to 30 age and sex-matched controls. Potential relationship of both markers with disease activity assessed using Disease activity score-28 joints (DAS-28), seropositivity (Rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA)), functional classification assessed using modified health assessment questionnaire (MHAQ), radiographic progression assessed using Larsen score and treatment was investigated. ResultsThe study included 60 patients; 54 (90 %) females and 6 (10 %) males with a mean age of 42.6 ± 10.1 years and disease duration of 7.5 ± 6.4 years. Their mean DAS-28 was 4.6 ± 1.0, their MHAQ was 1 ± 0.5 and their Larsen score was 41.3 ± 9.9. The mean of Gal-1 and Gal-4 were both significantly lower in RA patients in comparison to control group (4.4 ± 1.5 ng/ml vs 38.1 ± 25.5 ng/ml and 1.2 ± 0.7 ng/ml; p < 0.001vs 8.1 ± 7.0 ng/ml; p < 0.001 respectively. At a cut off value ≤7.7 for Gal-1 and ≤2.3 for Gal-4 was successfully able to differentiate between RA patients and control group. There was no correlation between both Gal-1 & Gal-4 and DAS-28, MHAQ, Larsen score, RF or ACPA titres. ConclusionGal-1 & 4 serum levels have a potential role as diagnostic markers in patients with RA. Both markers however cannot be regarded as disease activity or severity markers.

Comprehensive genetic and functional analyses of Fc gamma receptors influence on response to rituximab therapy for autoimmunity.

Rituximab is widely used to treat autoimmunity but clinical response varies. Efficacy is determined by the efficiency of B-cell depletion, which may depend on various Fc gamma receptor (FcγR)-dependent mechanisms. Study of FcγR is challenging due to the complexity of the FCGR genetic locus. We sought to assess the effect of FCGR variants on clinical response, B-cell depletion and NK-cell-mediated killing in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). A longitudinal cohort study was conducted in 835 patients [RA=573; SLE=262]. Clinical outcome measures were two-component disease activity score in 28-joints (2C-DAS28CRP) for RA and British Isles Lupus Assessment Group (BILAG)-2004 major clinical response (MCR) for SLE at 6 months. B-cells were evaluated by highly-sensitive flow cytometry. Single nucleotide polymorphism and copy number variation for genes encoding five FcγRs were measured using multiplex ligation-dependent probe amplification. Exvivo studies assessed NK-cell antibody-dependent cellular cytotoxicity (ADCC) and FcγR expression. In RA, carriage of FCGR3A-158V and increased FCGR3A-158V copies were associated with greater 2C-DAS28CRP response (adjusted for baseline 2C-DAS28CRP). In SLE, MCR was associated with increased FCGR3A-158V, OR 1.64 (95% CI 1.12-2.41) and FCGR2C-ORF OR 1.93 (95% CI 1.09-3.40) copies. 236/413 (57%) patients with B-cell data achieved complete depletion. Homozygosity for FCGR3A-158V and increased FCGR3A-158V copies were associated with complete depletion in combined analyses. FCGR3A genotype was associated with rituximab-induced ADCC, and increased NK-cell FcγRIIIa expression was associated with improved clinical response and depletion invivo. Furthermore, disease status and concomitant therapies impacted both NK-cell FcγRIIIa expression and ADCC. FcγRIIIa is the major low affinity FcγR associated with rituximab response. Increased copies of the FCGR3A-158V allele (higher affinity for IgG1), influences clinical and biological responses to rituximab in autoimmunity. Enhancing FcγR-effector functions could improve the next generation of CD20-depleting therapies and genotyping may stratify patients for optimal treatment protocols. Medical Research Council, National Institute for Health and Care Research, Versus Arthritis.

Analysis of comorbidity in rheumatoid arthritis–associated interstitial lung disease: a nested case-cohort study

ObjectivesTo describe comorbid conditions in patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and to analyze factors associated with multimorbidity. MethodsNested case-cohort study of 2 prospective cohorts: one with RA-ILD (cases) and another with RA but not ILD (controls). The cohorts were matched for age, sex, and time since diagnosis. Multimorbidity was defined as the co-occurrence of 2 or more chronic diseases, in addition to RA and ILD. We evaluated the comorbid conditions included in the Charlson Comorbidity Index, cardiovascular risk factors, neuropsychiatric conditions, and other frequent conditions in RA. We also recorded clinical-laboratory variables, inflammatory activity according to the 28-joint Disease Activity Score, C-reactive protein (CRP), physical function, and pulmonary function. We performed 2 multivariate analyses to identify factors associated with multimorbidity in RA and RA-ILD. ResultsThe final study population comprised 110 cases and 104 controls. Multimorbidity was more frequent among cases than controls (80 [72.7] vs 60 [57.7]; p = 0.021). In both groups, multimorbidity was associated with ILD (OR [95% CI] 1.92 [1.03–3.59]; p = 0.039), age (OR [95% CI] 1.05 [1.01–1.08]; p = 0.004), CRP (OR [95% CI] 1.16 [1.05–1.29]; p = 0.003), and erosions (OR [95% CI] 1.05 [1.01–1.08]; p = 0.004); in the cases, it was associated with CRP (OR [95% CI] 1.17 [1.01–1.35]; p = 0.027), anti–citrullinated peptide antibody (OR [95% CI] 1.23 [1.14–13.02]; p = 0.049), and forced vital capacity (OR [95% CI] 0.79 [0.96–0.99]; p = 0.036). ConclusionIn patients with RA, multimorbidity was associated with ILD, systemic inflammation, and advanced age.

Clinical Advantage of Attaining Index-Based Remission Prior to Composite Remission in Treating Rheumatoid Arthritis

Background and objectivesThe clinical advantage of targeting index-based remission prior to Boolean remission was evaluated retrospectively. Materials and methodsA total of 578 patients with rheumatoid arthritis (RA), who were treated for more than three years, were recruited. Patients who were treated to targeted index-based remission and composite measure remission criteria such as Boolean remission from the first consultation were divided according to the turn of attaining Boolean remission and index-based remission: G-IBR, a group that matched index-based remission at the same time Boolean remission is attained or earlier; G-BR_IF, a group that attained Boolean remission followed by index-based remission or failed; G-IR_BF, a group that could not attain Boolean remission despite attaining index-based remission; G-BothF, a group that failed to attain either Boolean remission or index-based remission. Background factors were statistically compared among groups. The Boolean remission rate in patients who attained index-based remission (BRR) and the rate of failure to attain index-based remission in patients who failed to attain Boolean remission (BFR) were statistically evaluated. ResultsGroups comprising 225, 231, and 482 in G-IBR; 160, 154, and 8 in G-BR_IF; 18, 18, and 75 in G-IR_BF; and 175, 175, and 13 in G-BothF when indexing the clinical disease activity index (CDAI), simplified disease activity index (SDAI), and 28-joints disease activity score with C-reactive protein (DAS28-CRP), respectively. Disease activity indices’ scores after Boolean remission were demonstrated to be significantly higher in the G-BR_IF group than in the G-IBR group. BRR was 92.6%, 92.8%, and 86.5%, while BFR was 71.3%, 71.3%, and 13.8% when indexing CDAI, SDAI, and DAS28-CRP, respectively. ConclusionsTargeting CDAI and SDAI remission prior to Boolean remission contributes to a stable clinical course.

Assessment of Post-Dengue Rheumatic Symptoms Using the WOMAC and DAS-28 Questionnaires in a Honduran Population after a Four-Month Follow-Up.

Introduction: Alphaviruses may cause arthritis, but there is a lack of studies assessing it in flaviviruses such as dengue. Through the 28 Joint Disease Activity Score (DAS-28), incorporating swollen joint counts, and through the Arthritis Index from Western Ontario and McMaster Universities (WOMAC), we assessed pain, stiffness, and dimensions of arthritic function in post-DENV patients. Methods: Prospective study of a cohort of participants who were diagnosed with dengue in centres in Honduras from December 2019 to February 2020, with a follow-up period of 4 months to evaluate post-dengue rheumatological disease through the WOMAC and DAS-28 questionnaires. Results: After a four-month follow-up phase with 281 participants, the final cohort comprised 58.8% women and 41.20% men. After the follow-up, 63.02% persisted with the clinical findings. According to WOMAC, joint involvement was higher in women with (58.76%) (p < 0.0001) these symptoms or functional limitations when performing daily activities were limited to pain when walking (34.81% vs. 5.51%), climbing or descending stairs (36.46% vs. 8.66%), and at night at bedtime (28.73% vs. 7.08%). With the DAS-28, we found at least one alteration with inflammation or pain in 14.91% of the participants, primarily women (p < 0.01). Discussion: Joint involvement was high during the dengue epidemic in 2019. We observed a significant proportion of women with inflammation and joint pain, showing that dengue may lead to the development of chronic rheumatological findings, although lower than in CHIKV, still affecting everyday life and, consequently, their quality of life. Additional long-term evaluation studies after dengue are required.

Cross-cultural and clinical validation of the MDHAQ/RAPID3 questionnaire in electronic format for a Brazilian population of patients with rheumatoid arthritis

BackgroundPatients with rheumatologic diseases are monitored fundamentally through metric tools or index calculated from clinical data and patient exams, which allow us to assess the severity of the disease and guide the therapeutic decision. In rheumatoid arthritis (RA), for treatment to be optimized and considered effective, periodic assessment with composite disease activity index and a 'treat-to-target' approach is required. The Routine Assessment of Patient Index Data 3 (RAPID3) in the Multidimensional Health Assessment Questionnaire (MDHAQ) includes only three measures based on the central patient self-reported dataset and can be used in a 'treat-to-target' approach analogous to the Clinical Disease Activity Index (CDAI) and the Disease Activity Score 28-joints (DAS28). This tool, however, has not undergone cross-cultural or clinical validation in Brazil. In this research, we performed the MDHAQ cross-cultural and clinical validation for the Brazilian population of RA patients.MethodsThe Portuguese version of the MDHAQ was created identically in an electronic questionnaire and underwent a cross-cultural validation process with 38 participants. Test–retest was performed in 29 patients. Further, a clinical validation with 129 Rheumatoid Arthritis patients was performed. Electronic MDHAQ was answered through an online platform. We also collected socioeconomic data as well as other clinical (CDAI, SDAI, DAS28) and functional (HAQ) scores during the face-to-face assessment of patients.ResultsMDHAQ/RAPID3 maintained semantic, idiomatic, as well as conceptual and experience equivalence for the Brazilian population, with 92% acceptance of participants. It showed test–retest reliability, adequate internal consistency (Cronbach's α 0.85) and correlation of the scores obtained with adequate association with the DAS28 gold standard. RAPID3 also had high sensitivity (98%), adequate specificity (48%), high negative predictive value (92%) and negative post-test probability of 8%, attributes expected for a test tool for population screening.ConclusionThe use of MDHAQ/RAPID3 associated with traditional clinical measures can adequately allow for remote follow-up based on the 'treat-to-target' approach with performance comparable to the gold standard DAS28, being a viable tool in the sample of Brazilian patients with RA in the current context of telehealth.

Using the derived 28-joint disease activity score patient-reported components (DAS28-P) index as a discriminatory measure of response to disease-modifying anti-rheumatic drug therapy in early rheumatoid arthritis

BackgroundThe 28-joint disease activity score (DAS28) is a widely used measure to assess disease activity in rheumatoid arthritis (RA). The DAS28-P index, a derived proportion of the patient-reported components (joint tenderness and patient global assessment) within the DAS28, has been utilized as a discriminatory measure of non-inflammatory pain mechanisms in RA. This study aimed to evaluate the use of the DAS28-P index as a predictor of treatment response in early RA.MethodsPatients with early RA enrolled in a supplemental fish oil clinical trial received a combination of disease-modifying anti-rheumatic drugs (DMARDs) according to a ‘treat-to-target’ protocol. First, consecutive measures of the DAS28-P index, derived from the DAS28-erythrocyte sedimentation rate (DAS28-ESR), at each visit over a 1-year period were estimated for each patient. Then, distinct subgroups of treatment responders based on the trajectories of the DAS28-P indices were identified using bivariate k-means cluster analysis. Data on baseline predictors as well as longitudinal outcomes of disease impact and DMARD use over a 1-year period and radiographic progression over a 3-year period were collected and analyzed using a random intercept, population-averaged generalized estimating equation model.Results121 patients were included (74% female; mean age of 57; median of 16 weeks of active disease) and a 3-cluster model was identified—the ‘Responders’ group (n = 58; 48%), the ‘Partial Responders’ group (n = 32; 26%), and the ‘Non-Responders’ group (n = 31; 26%). The ‘Partial Responders’ group had consistently higher proportions of the DAS28-P index throughout the study period and had minimal radiographic progression over time, with the lowest joint erosion score of 0.9 [95% confidence interval (CI) 0.2, 1.6], observed at the 3-year follow-up. At 52 weeks, the methotrexate dose was higher for both ‘Partial Responders’ and ‘Non-Responders’ groups (18.5 mg [95% CI 15.5, 21.5] and 18.6 mg [95% CI 15.3, 21.8] respectively), when compared with the ‘Responders’ group (12.8 mg [95% CI 14.7, 20.9]).ConclusionsPersistently high DAS28-P index scores are useful to distinguish poor patient global assessment and excessive treatment escalation in early RA, suggestive of underlying non-inflammatory pain contributing to higher disease activity score. Early identification of patients with discordant subjective and objective components of composite disease activity measures may allow better tailoring of treatment in RA.

Inflammatory profile of incident cases of late-onset compared with young-onset rheumatoid arthritis: A nested cohort study.

To describe the characteristics of patients between late-onset rheumatoid arthritis (LORA) with young-onset (YORA), and analyze their association with cumulative inflammatory burden. We performed a nested cohort study in a prospective cohort comprising 110 patients with rheumatoid arthritis (RA) and 110 age- and sex-matched controls. The main variable was cumulative inflammatory activity according to the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). High activity was defined as DAS28 ≥ 3.2 and low activity as DAS28 < 3.2. The other variables recorded were inflammatory cytokines, physical function, and comorbid conditions. Two multivariate models were run to identify factors associated with cumulative inflammatory activity. A total of 22/110 patients (20%) met the criteria for LORA (≥ 60 years). Patients with LORA more frequently had comorbid conditions than patients with YORA and controls. Compared with YORA patients, more LORA patients had cumulative high inflammatory activity from onset [13 (59%) vs. 28 (31%); p = 0.018] and high values for CRP (p = 0.039) and IL-6 (p = 0.045). Cumulative high inflammatory activity in patients with RA was associated with LORA [OR (95% CI) 4.69 (1.49-10.71); p = 0.008], smoking [OR (95% CI) 2.07 (1.13-3.78); p = 0.017], anti-citrullinated peptide antibody [OR (95% CI) 3.24 (1.15-9.13); p = 0.025], average Health Assessment Questionnaire (HAQ) score [OR (95% CI) 2.09 (1.03-14.23); p = 0.034], and physical activity [OR (95% CI) 0.99 (0.99-0.99); p = 0.010]. The second model revealed similar associations with inflammatory activity in patients with LORA. Control of inflammation after diagnosis is poorer and comorbidity more frequent in patients with LORA than in YORA patients and healthy controls.

Lower odds of remission among women with rheumatoid arthritis: A cohort study in the Swiss Clinical Quality Management cohort.

ObjectiveTo compare the likelihood of achieving remission between men and women with rheumatoid arthritis (RA) after starting their first biologic or targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD).MethodsThis cohort study in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry included RA patients starting their first b/tsDMARD (1997-31/04/2018). The odds of achieving remission at ≤12-months, defined by disease activity score 28-joints (DAS28) <2.6, were compared between men and women. Secondary analyses were adjusted for age and seropositivity, and we investigated potential mediators or factors that could explain the main findings.ResultsThe study included 2839 (76.3%) women and 883 (23.7%) men with RA. Compared to women, men were older at diagnosis and b/tsDMARD start, but had shorter time from diagnosis to b/tsDMARD (3.4 versus 5.0 years, p<0.001), and they had lower DAS28 at b/tsDMARD start. Compared to women, men had 21% increased odds of achieving DAS28-remission, with odds ratio (OR) 1.21, 95% confidence interval (CI) 1.02–1.42. Adjusting for age and seropositivity yielded similar findings (adjusted OR 1.24, 95%CI 1.05–1.46). Analyses of potential mediators suggested that the observed effect may be explained by the shorter disease duration and lower DAS28 at treatment initiation in men versus women.ConclusionMen started b/tsDMARD earlier than women, particularly regarding disease duration and disease activity (DAS28), and had higher odds of reaching remission. This highlights the importance of early initiation of second line treatments, and suggests to target an earlier stage of disease in women to match the benefits observed in men.

Chinese registry of rheumatoid arthritis (CREDIT) V: sex impacts rheumatoid arthritis in Chinese patients.

The impact of sex on the clinical manifestations of rheumatoid arthritis (RA) were diversely reported in the literature. The Chinese Registry of rhEumatoiD arthrITis provides a platform for the investigation of this issue in Chinese patients. Demographic and clinical parameters were collected from all enrolled patients with RA and from patients with early RA (disease duration ≤6 months). The differences in data regarding disease activity, comorbidities, and medications for RA were compared between men and women. The proportions of patients who achieved remission and low disease activity were compared at enrollment and during 3-, 6-, and 12-month follow-up visits. A total of 11,564 patients were enrolled, 83.6% of whom were female. In all the enrolled patients and patients with early RA, C-reactive protein (CRP, 12.0 vs . 6.7 mg/L), pain visual analogue scale (4.8 vs . 4.5), patient's and physician's global assessment (4.9 vs . 4.5 and 4.9 vs . 4.5), 28-joint disease activity score using DAS28-CRP (4.3 vs . 4.0) simplified disease activity index (21.9 vs . 19.9), and clinical disease activity index (19.3 vs . 18.0) were significantly higher in men than in women. Additionally, the swollen joint count/tender joint count and DAS28 using erythrocyte sedimentation rate were higher in male patients than in female patients with early RA. More female patients with early RA reached the treatment target at baseline than male patients (23.4% vs . 18.2%, assessed by CDAI). At 3 months, 6 months, and 12 months, the proportion of remission and treatment target achievement was similar in both sexes. Coronary artery disease (CAD) and stroke were more frequent in men than in women. In Chinese patients with RA, men were found to have more active disease, as well as more cases of CAD and stroke. Therefore, sex should be carefully considered during the personalization of RA treatment.

Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials.

IntroductionThe Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported outcome tool recommended for the assessment of disease activity in patients with rheumatoid arthritis (RA) in clinical practice. This analysis evaluated the long-term effect of upadacitinib vs. comparators on RAPID3 scores in patients with RA in the phase 3 SELECT clinical trial program.MethodsThis post hoc analysis included data from five randomized controlled trials (RCTs) in patients receiving upadacitinib 15 mg or 30 mg once daily (QD) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The proportions of patients reporting RAPID3 remission (scores ≤ 3) were assessed at week 60. Correlations between absolute scores for RAPID3 and Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and 28-joint Disease Activity Score with C-reactive protein (DAS28[CRP]) at week 60 were assessed using Spearman correlation coefficients.ResultsA total of 3117 patients were included from the SELECT-NEXT, -BEYOND, -MONOTHERAPY, -COMPARE, and -EARLY trials. By week 60, 32–52% of methotrexate-naïve and csDMARD inadequate responder (IR) patients treated with either upadacitinib 15 mg QD or upadacitinib 30 mg QD reported RAPID3 scores consistent with remission. The proportions were slightly lower in the biologic DMARD-IR SELECT-BEYOND population (19–28%). RAPID3 scores highly correlated (Spearman correlation values ≥ 0.58) with CDAI, SDAI, and DAS28(CRP) scores through week 60 (all p < 0.001).ConclusionsUpadacitinib, as monotherapy or in combination with csDMARDs, was associated with patient-reported remission assessed by RAPID3 over 60 weeks across the SELECT RCTs in patients with RA.Trial registrationSELECT-BEYOND (NCT02706847); SELECT-NEXT (NCT02675426); SELECT-MONOTHERAPY (NCT02706951); SELECT-EARLY (NCT02706873); SELECT-COMPARE (NCT02629159).Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00483-4.

The role of ultrasonographic synovial assessment in rheumatoid arthritis patients with concomitant fibromyalgia.

This study aimed to compare the prevalence and musculoskeletal ultrasonography (US) findings of rheumatoid arthritis (RA) patients with concomitant fibromyalgia (FM) according to the 1990 American College of Rheumatology (ACR) FM classification criteria or the 2016 ACR FM diagnostic criteria. This cross-sectional study included 63 patients (17 males, 46 females; mean age: 48.2±7.1 years; range, 18 to 62 years) with RA. Medical history and laboratory data were obtained from electronic records. Clinical examination, composite disease activity measures, functional status, and the German 7-joint ultrasound score were assessed to evaluate disease activity and synovial inflammation. The patients were divided into three groups: patients who met only the 2016 ACR criteria, patients who met only the 1990 ACR criteria, and patients who met both criteria. In patients with RA, concomitant FM prevalence was 34.9% according to the 2016 ACR FM diagnostic criteria versus 23.8% according to the 1990 ACR FM classification criteria. Rheumatoid arthritis patients with FM had high tender joint count and disease activity scores, while musculoskeletal US findings were similar. Patients who met only the 2016 ACR FM diagnostic criteria had significantly higher gray-scale US and power Doppler US synovitis scores than patients who satisfied only ACR 1990 FM classification criteria (p=0.03 and p=0.02, respectively). Synovial inflammation is a prominent sign in RA patients diagnosed with FM according to the 2016 ACR FM diagnostic criteria. The higher disease activity seen in the presence of FM in RA patients is associated with FM rather than synovitis.

Tofacitinib treatment modulates the levels of several inflammation-related plasma proteins in rheumatoid arthritis and baseline levels of soluble biomarkers associate with the treatment response.

The data on the effects of tofacitinib on soluble proteins in patients with rheumatoid arthritis (RA) is currently very limited. We analyzed how tofacitinib treatment and thus inhibition of the Janus kinase-signal transducer and activation of transcription pathway affects the in vivo levels of inflammation-related plasma proteins in RA patients. In this study, 16 patients with active RA [28-joint disease activity score (DAS28) >3.2] despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) started tofacitinib treatment 5 mg twice daily. Levels of 92 inflammation-related plasma proteins were determined by proximity extension assay at baseline and at 3 months. Tofacitinib treatment for 3 months, in csDMARD background, decreased the mean DAS28 from 4.4 to 2.6 (P < 0.001). Marked (>20%) and statistically significant (P < 0.05) changes were found in the levels of 21 proteins, 18 of which decreased and 3 increased. Of these proteins, 17 are directly involved in inflammatory responses or in the cellular response to cytokines. The highest (>50%) decrease was observed for interleukin-6 (IL-6), C-X-C motif chemokine ligand 1, matrix metalloproteinase-1, and AXIN1. Higher baseline levels of IL-6 and lower levels of C-C motif chemokine 11 and Delta and Notch-like epidermal growth factor-related receptors were associated with DAS28 improvement. Our results indicate that tofacitinib downregulates several proinflammatory plasma proteins that may contribute to the clinical efficacy of tofacitinib. In addition, soluble biomarkers may predict the treatment response to tofacitinib.

Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study

ObjectivesTo assess the efficacy and safety of olokizumab (OKZ), a monoclonal antibody against the interleukin-6 (IL-6) cytokine, versus placebo (PBO) in patients with prior inadequate response to tumour necrosis factor...

Minimal disease activity and remission in patients with psoriatic arthritis with elevated body mass index: an observational cohort study in the Swiss Clinical Quality Management cohort

ObjectiveTo assess the impact of elevated body mass index (BMI) in the achievement of minimal disease activity (MDA) and several definitions of remission in patients with psoriatic arthritis (PsA) in...

Sex and gender impact on achievement of remission in people with rheumatoid arthritis in Switzerland: a cohort study

<h2>Abstract</h2><h3>Background</h3> Sex and gender can play a role in rheumatoid arthritis; thus, we aimed to compare the likelihood of reaching remission in men and women with rheumatoid arthritis. <h3>Methods</h3> This observational cohort study was done using the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry (1997–2019). The study included adults (older than 18 years) with rheumatoid arthritis who started their first biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) before April 30, 2018. Those without a recorded baseline visit were excluded. The study exposure was sex (biological) and gender (social construct). Exposure data were recorded as male and female but referred to here as men and women. Patient baseline characteristics were compared between men and women. Logistic regression was used to compare the odds of reaching remission at 12 months or less (defined by the Disease Activity Score 28-joints [DAS28] of <2·6) in men versus women. We also investigated potential mediators (baseline DAS28 [≥3·2 <i>vs</i> <3·2], disease duration [>2 <i>vs</i> ≤2 years], elevated BMI [≥25 <i>vs</i> BMI <25], conventional synthetic DMARD use at index date [yes <i>vs</i> no], and steroid use at index date [yes <i>vs</i> no]) using logistic regression. <h3>Findings</h3> We included 3722 patients with rheumatoid arthritis who were new users of biologic or targeted synthetic DMARDs. 2839 (76·3%) patients were women and 883 (23·7%) were men. The median age was 56·8 years (IQR 46·9–65·2). Men were older at diagnosis and at the start of treatment and had a shorter time from diagnosis to starting their first biologic or targeted synthetic DMARD (3·43 years [IQR 1·15–9·93] <i>vs</i> 4·95 years [1·68–12·03] in women; p<0·0001). At baseline, women had significantly higher disease activity (DAS28 4·40 [SD 1·36] <i>vs</i> 4·17 [1·52] in men; p=0·0001) and worse Health Assessment Questionnaire scores (1·00 [IQR 0·50–1·62] <i>vs</i> 0·88 [0·38–1·38] in men; p<0·0001) and tender joints (5·00 [IQR 2·00–11·00] <i>vs</i> 4·00 [1·00–10·00] in men; p=0·020). Compared with women, men were more likely to reach DAS28 remission at 12 months or less (odds ratio [OR] 1·21, 95% CI 1·02–1·42; p=0·026). Adjusting for age and seropositivity resulted in similar findings (adjusted OR 1·24, 1·05–1·46; p=0·012). Mediation analyses showed lower odds of baseline DAS28 at 3·2 or higher (OR 0·65, 0·53–0·78; p<0·0001) and disease duration of more than 2 years (OR 0·71, 0·60–0·83; p<0·0001) in men compared with women. Further mediation analyses identified baseline DAS28 and disease duration as factors that might explain the association between sex, gender, and DAS28 remission. <h3>Interpretation</h3> Among patients with rheumatoid arthritis who received biologic or targeted synthetic DMARDs, men with rheumatoid arthritis had higher odds of reaching remission than women, which could be explained by the earlier escalation to treatment with biologic or targeted synthetic DMARDs in men versus women. This finding suggests the possibility that starting treatment at earlier stage of disease in women may be beneficial and reduce the observed disparity. <h3>Funding</h3> None.

The Safety and Effectiveness of Infliximab Biosimilar in Managing Rheumatoid Arthritis: A Real-Life Experience from Jordan.

Background Infliximab (IFX) biosimilar was the first biosimilar approved in Jordan in 2014, with limited evidence of its safety and effectiveness from the Middle East and North Africa (MENA) region. Thus, this study aimed to evaluate the safety and effectiveness of IFX biosimilar in active rheumatoid arthritis (RA) patients over 34 weeks by investigating (1) the adverse events (AEs), serious adverse events (SAEs), and therapy discontinuation and (2) the score changes of the 28-Joint Disease Activity Score (DAS28) and the Health Assessment Questionnaire Disability Index (HAQ-DI). Methods This multicenter prospective cohort study collected clinical parameters within hospital settings every four weeks. The numbers and percentages of observed AEs and SAEs were informed. The DAS28 utilizing Erythrocyte Sedimentation Rate (ESR), HAQ-DI, and ESR were reported at baseline and 14th and 30th weeks; thus, they were reported as means (SD). Results A total of 22 RA patients were enrolled and initiated IFX biosimilar, of which nine (41.0%) discontinued the study, but their data were analyzed up to the point of withdrawal. A total of 35 AEs were reported in 14 patients, including two (5.7%) SAEs. None of the participants discontinued treatment due to AEs. The mean (SD) score of DAS28-ESR significantly decreased from 6.55 (1.16) at baseline to 4.59 (1.45) at week 14 (p < 0.0001) and to 4.77 (1.09) at week 30 (p < 0.0001). Similarly, the mean (SD) HAQ-DI score significantly decreased from 0.95 (0.74) at baseline to 0.48 (0.62) at week 14 (p=0.008) and to 0.71 (0.78) at week 30 (p=0.483). The mean (SD) value of ESR decreased from 58.75 (26.94) at baseline to 47.92 (33.89) at week 14 (p=0.082) and to 39.83 (17.38) at week 30 (p=0.005). Conclusion IFX biosimilar demonstrated safety and effectiveness in managing RA patients bringing real-world clinical support for biosimilars' role in rheumatology.

The effect of a tight control regime with monthly follow-up on remission rates and reported pain in early rheumatoid arthritis.

To determine whether a tight control (TC) regime with monthly consultations to the physician for the first 6months, could increase remission rate and improve reported pain of patients with early rheumatoid arthritis (RA). In this single-centre, TC study, with monthly visits to the physician, a cohort of 100 patients with early RA was consecutively included. They were compared with a reference cohort of 100 patients from the same clinic that had been conventionally managed. The patients were followed for 2years. The patients in the TC cohort had lower 28- joints disease activity score (DAS28) at three, six, 12 and 24months, compared with the conventionally managed cohort, p≤0.001. At 12months, 71% in the TC cohort versus 46% in the conventional cohort were in remission (DAS28<2.6) and at 24months 68% versus 49% respectively, p<0.05. The TC cohort reported less pain at three, six, 12 and 24months, p<0.001. Multiple logistical regression analyses adjusted for, respectively, age, disease duration, pharmacological treatment, DAS28 and visual analogue scale pain at inclusion, revealed that participation in the TC cohort had an independent positive association with remission at 12 and 24months and with acceptable pain at 24months. The intensive follow-up schedule for patients with early RA improved remission and led to improvement in reported pain and physical function. The positive effect of a TC regime in early disease may be due to increased empowerment, developed by meeting health professionals frequently.

Long-Term Efficacy and Safety of Risankizumab in Patients with Active Psoriatic Arthritis: Results from a 76-Week Phase 2 Randomized Trial.

IntroductionThe objective of this work was to assess the efficacy and safety of risankizumab in psoriatic arthritis (PsA) over 76 weeks.MethodsIn this double-blind, dose-ranging phase 2 study, adults with active PsA were randomized 2:2:2:1:2 to risankizumab 150 mg at weeks 0, 4, 8, 12, and 16 (arm 1), 150 mg at weeks 0, 4, and 16 (arm 2), 150 mg at weeks 0 and 12 (arm 3), 75 mg at week 0 (arm 4), or placebo (arm 5). Patients completing week 24 could receive risankizumab 150 mg in a 52-week open-label extension study. Efficacy assessments included American College of Rheumatology (ACR) responses, Psoriasis Area Severity Index (PASI) responses, minimal disease activity (MDA), and 28-joint Disease Activity Score based on C-reactive protein (DAS28[CRP]).ResultsOf 185 randomized patients, 173 (93.5%) completed week 16 and 145 (78.4%) entered the open-label extension. Significantly more patients in each risankizumab arm achieved ACR20 at week 16 versus placebo (primary endpoint: pooled arms 1 + 2 [59.5%] versus placebo [35.7%]; treatment difference [90% CI] 24.0 [9.3, 38.7]; P = 0.007). Similarly, significantly more patients in most risankizumab arms achieved ACR20/50/70, PASI75/90/100, MDA, and greater improvements in DAS28(CRP) versus placebo at week 16. These benefits of risankizumab were maintained long term. Treatment-emergent adverse events were comparable across treatment arms. Risankizumab 150 mg was well tolerated over 76 weeks.ConclusionsRisankizumab improved joint and skin symptoms versus placebo in patients with active PsA over 16 weeks; improvements were sustained long term. Risankizumab was well tolerated over the long term with no new safety findings.Trial Registration NumbersNCT02719171 and NCT02986373.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00474-5.