Rheumatology and Therapy最新文献

Introduction: A matching-adjusted indirect comparison (MAIC) was conducted to assess the relative efficacy at 52 weeks (Wk52) of bimekizumab 160 mg every 4 weeks (Q4W) and ustekinumab 45 or 90 mg every 12 weeks (Q12W) in patients with psoriatic arthritis (PsA) who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or who had a previous inadequate response or an intolerance to tumor necrosis factor inhibitors (TNFi-IR).

Methods: Relevant trials were systematically identified. Individual patient data from the bimekizumab trials BE OPTIMAL (NCT03895203; N = 431) and BE COMPLETE (NCT03896581; N = 267) were matched with summary data on patients receiving ustekinumab in the PSUMMIT 1 trial (NCT01009086; 45 mg, N = 205; 90 mg; N = 204) and a subgroup of TNFi-IR patients receiving ustekinumab in the PSUMMIT 2 trial (NCT01077362; 45 mg, N = 60; 90 mg, N = 58), respectively. Patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of the ustekinumab trial patients. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Non-placebo-adjusted comparisons of recalculated bimekizumab and ustekinumab outcomes for the American College of Rheumatology (ACR) 20/50/70 response criteria (non-responder imputation) were analyzed.

Results: In patients who were bDMARD naïve, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (odds ratio [95% confidence interval] 45 mg: 2.14 [1.35, 3.40]; 90 mg: 1.98 [1.24, 3.16]), ACR50 (45 mg: 2.74 [1.75, 4.29]; 90 mg: 2.29 [1.48, 3.55]), and ACR70 (45 mg: 3.33 [2.04, 5.46]; 90 mg: 3.05 [1.89, 4.91]). In patients who were TNFi-IR, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (45 mg: 4.17 [2.13, 8.16]; 90 mg: 4.19 [2.07, 8.49]), ACR50 (45 mg: 5.00 [2.26, 11.05]; 90 mg: 3.86 [1.70, 8.79]), and ACR70 (45 mg: 9.85 [2.79, 34.79]; 90 mg: 6.29 [1.98, 20.04]).

Conclusions: Using MAIC, bimekizumab showed greater efficacy than ustekinumab in achieving all ACR responses in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52.

Trial registration: NCT03895203, NCT03896581, NCT01009086, NCT01077362.

Introduction: The study aimed to determine the efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in the treatment of polymyalgia rheumatica (PMR) complicated by rheumatoid arthritis (RA).

Methods: Patients with PMR which could be classified as RA and who were treated with bDMARDs were included in the analysis. The primary endpoint was the clinical Polymyalgia Rheumatica Activity Score (Clin-PMR-AS) after 26 weeks of treatment, and the secondary endpoint was adverse events during the observation period.

Results: A total of 203 patients with PMR which was resistant or intolerant to glucocorticoids and could be classified as RA were receiving bDMARDs and were enrolled in the study. There were 83, 82, and 38 patients in the tumor necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL-6Ri), and cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4-Ig) groups, respectively. Twenty-six weeks after bDMARD initiation, Clin-PMR-AS levels were significantly lower in the IL-6Ri group as compared to other groups. Multiple regression analysis was performed with Clin-PMR-AS as the objective variable. Body mass index (BMI), history of bDMARDs, and IL-6Ri use were identified as factors involved in Clin-PMR-AS. After adjustment for group characteristics using inverse probability of treatment weighting with propensity scores, the Clin-PMR-AS score at 26 weeks was significantly lower in the IL-6Ri group (9.0) than in both the TNFi (12.4, p = 0.004) and CTLA4-Ig (15.9, p = 0.003) group.

Conclusion: IL-6Ri may potentially improve the disease activity of PMR compared to other bDMARDs.

Introduction: High baseline neutrophil-to-lymphocyte ratio (NLR) in rheumatoid arthritis (RA) has been associated with positive responses to biologic tumor necrosis factor inhibition and negative responses to conventional synthetic disease-modifying antirheumatic drug (csDMARD) triple therapy. Datasets from three randomized clinical trials in patients with RA were used to test the hypothesis that baseline NLR is associated with improved clinical response to filgotinib in methotrexate (MTX)-naïve or MTX-experienced RA populations.

Methods: Patients from FINCH 1 (inadequate response to MTX, MTX-IR; NCT02889796), FINCH 2 (inadequate response to biologic DMARDs; NCT02873936), and FINCH 3 (MTX-naïve; NCT02886728) were classified as baseline NLR-High or baseline NLR-Low based on a previously published cut point of 2.7. In total, 3365 patients were included across the three studies. Differences in clinical outcomes and patient-reported outcomes (PROs) were determined using linear-regression models.

Results: Control-arm patients (placebo + MTX/placebo + csDMARD) classified as NLR-High exhibited worse continuous clinical and PRO responses at week 12 across clinical trials compared to NLR-Low patients. In contrast, NLR-High patients who received FIL 200 mg + MTX/csDMARD exhibited consistently better responses after 12 weeks compared to NLR-Low patients across clinical trials, clinical endpoints, and PROs. These trends were most prominent among the MTX-IR population.

Conclusion: The 2.7 baseline NLR cut point could be used to enrich for patients most likely to benefit from the addition of filgotinib to background MTX/csDMARD. Use of baseline NLR as part of therapeutic decision-making would not require additional diagnostics and could contribute to improved outcomes for patients with RA.

Trial registration: Clinicaltrials.gov: NCT02889796; NCT02873936; NCT02886728.

Introduction: The relative efficacy of bimekizumab and risankizumab in patients with PsA who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR) was assessed at 52 weeks (Wk52) using matching-adjusted indirect comparisons (MAIC).

Methods: Relevant trials were systematically identified. For patients who were bDMARD naïve, individual patient data (IPD) from BE OPTIMAL (NCT03895203; N = 431) were matched with summary data from KEEPsAKE-1 (NCT03675308; N = 483). For patients who were TNFi-IR, IPD from BE COMPLETE (NCT03896581; N = 267) were matched with summary data from the TNFi-IR patient subgroup in KEEPsAKE-2 (NCT03671148; N = 106). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted to match the baseline characteristics of patients in the risankizumab trials. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Recalculated bimekizumab Wk52 outcomes for American College of Rheumatology (ACR) 20/50/70 response criteria and minimal disease activity (MDA) index (non-responder imputation) were compared with risankizumab outcomes via non-placebo-adjusted comparisons.

Results: In patients who were bDMARD naïve, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR50 (odds ratio [95% confidence interval]: 1.52 [1.11, 2.09]) and ACR70 (1.80 [1.29, 2.51]). In patients who were TNFi-IR, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR20 (1.78 [1.08, 2.96]), ACR50 (3.05 [1.74, 5.32]), ACR70 (3.69 [1.82, 7.46]), and MDA (2.43 [1.37, 4.32]).

Conclusions: Using MAIC, bimekizumab demonstrated a greater likelihood of efficacy in most ACR and MDA outcomes than risankizumab in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52.

Trial registration: NCT03895203, NCT03896581, NCT03675308, NCT03671148.

Introduction: The safety and efficacy of upadacitinib 15 mg (UPA15) through week 216 was evaluated in patients with rheumatoid arthritis (RA) from the long-term extension (LTE) of the phase 3 SELECT-CHOICE study.

Methods: Patients with RA refractory to biologic disease-modifying antirheumatic drugs (bDMARDs) were randomized to UPA15 or abatacept (ABA) for 24 weeks. During the open-label LTE, patients on ABA switched to UPA15 at week 24, and those on UPA15 continued treatment. The safety and efficacy of continuous UPA15, and ABA to UPA15, are summarized through week 216.

Results: The LTE was comprised of 91.4% (n = 277/303) of patients that initially received UPA15, and 89.6% (n = 277/309) that initially received ABA. Of patients on UPA15 in the LTE (n = 547), 28.3% (n = 155/547) discontinued the study drug by week 216. Relative to other adverse events of special interest, and largely consistent with previous findings at week 24, higher rates of serious infection, COVID-19, herpes zoster, and elevated creatine phosphokinase were reported, while rates of malignancy excluding nonmelanoma skin cancer (NMSC), NMSC, major adverse cardiovascular event (MACE), and venous thromboembolism (VTE) were low. Long-term safety data with UPA through week 216 aligned with previous observations and no new safety risks were identified, including in patients who switched from ABA to UPA15. Proportions of patients achieving 28-joint disease activity score based on C-reactive protein (DAS28[CRP]) < 2.6/ ≤ 3.2, clinical disease activity index (CDAI) and simple disease activity index (SDAI) low disease activity/remission, ≥ 20%/50%/70% improvement in the American College of Rheumatology (ACR20/50/70) response criteria, and Boolean remission were maintained or improved with UPA15 through week 216. Improvements in the Health Assessment Questionnaire-Disability Index (HAQ-DI), patient's assessment of pain, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were also maintained or improved with UPA15 through week 216. Across all efficacy endpoints, similar results were observed in patients who switched from ABA to UPA15 versus continuous UPA15. Patients with an inadequate response to ≥ 1 prior tumor necrosis factor (TNF) inhibitor (UPA15: n = 263/303, 86.8%; ABA to UPA15: n = 273/309, 88.3%) showed similar responses to the total population.

Conclusions: The long-term safety profile of UPA was consistent with previous findings and the broader RA clinical program. Compared to the primary analyses at week 24, efficacy responses were maintained or further improved with UPA15 through week 216 in patients with RA. Trial registration, ClinicalTrials.gov identifier: NCT03086343.

This Summary of Research overviews the results of a study that looked at patient-reported outcomes in the VOLTAIRE-RA trial (NCT02137226), originally published in Rheumatology and Therapy. A biosimilar is a biologic medicine made to be very similar to the original biologic medicine (also known as the reference product). The VOLTAIRE-RA trial compared the efficacy and safety of an adalimumab biosimilar (Cyltezo^®, adalimumab-admb) with the adalimumab reference product, Humira^®, in people with rheumatoid arthritis. As part of the VOLTAIRE-RA study, participants took either adalimumab-adbm or adalimumab reference product for 24 weeks. Patient-reported outcomes were captured after 12 weeks and after 24 weeks of treatment to assess the effects of treatment on each participant's health-related quality of life. People with rheumatoid arthritis who were given adalimumab-adbm or adalimumab reference product experienced similar clinically meaningful improvements in their health-related quality of life after 12 weeks of treatment. A high proportion of people in this trial who were given adalimumab-adbm or adalimumab reference product reported greater improvement versus a reference US population matched by age and sex. This is notable, as it represents a treatment goal that was difficult to achieve in earlier rheumatoid arthritis trials of non-biologic treatments.

Introduction: Patients with chronic refractory gout face a considerable burden of disease due to unexpected flares characterized by severe and debilitating pain, which can lead to chronic pain and joint damage. This study aimed to understand the symptoms and impacts of chronic refractory gout on health-related quality of life (HRQoL).

Methods: A targeted literature review was conducted to identify and review key articles describing the symptoms and impacts of gout, and articles examining the psychometric performance of the Medical Outcomes Survey Short Form-36 (SF-36) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in gout. Qualitative interviews were conducted with 20 participants with chronic refractory gout. The results were used to develop the conceptual model and determine the appropriateness of the SF-36 and HAQ-DI in evaluating HRQoL in this population.

Results: Most frequently reported symptoms included bodily pain (n = 18, 90.0%), joint swelling (n = 18, 90.0%), joint tenderness (n = 18, 90.0%), and joint pain (n = 16, 80.0%). Most frequently reported impacts were difficulties climbing a flight (n = 20, 100.0%) or several flights of stairs (n = 20, 100.0%), climbing five steps (n = 19, 95.0%), completing chores (n = 19, 95.0%), and running errands and shopping (n = 19, 95.0%). All assessed items from SF-36 and HAQ-DI were reported by ≥ 25% (n = 5) of participants and mapped sufficiently to concepts elicited by participants.

Conclusions: Patients with chronic refractory gout report symptoms and impacts that are highly bothersome and burdensome to everyday life. Items included in the HAQ-DI and SF-36 mapped directly to these symptoms and impacts and are relevant to understand the burden of disease of chronic refractory gout.

Introduction: Patients with rheumatoid arthritis (RA) may have an increased malignancy risk versus the general population, potentially elevated by biological disease-modifying antirheumatic drug (bDMARD) use. Using patient registry data, we determined malignancy risk, stratified by bDMARD use, among Japanese patients with RA versus the Japanese general population and investigated whether bDMARD use is a time-dependent risk factor for the development of malignancy.

Methods: Patients aged ≥ 18 years with ≥ 2 data entries of RA in the IORRA (Institute of Rheumatology, Rheumatoid Arthritis) patient registry, enrolled from January 2013-December 2018, were identified ('All RA' cohort). Patients were stratified into bDMARD (≥ 1 bDMARD received) or non-bDMARD (no history of bDMARDs) sub-cohorts. Malignancy incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) versus the Japanese general population were calculated. Risk of RA medication use was analyzed using a time-dependent Cox proportional hazards model, after adjusting for covariates.

Results: A total of 8020 patients were identified for the All RA cohort; 2187 and 5833 for the bDMARD and non-bDMARD sub-cohorts, respectively. For all three cohorts, incidence of overall malignancies was similar versus the Japanese general population. Incidence of specific malignancies was also similar, but incidence of lymphoma was higher for all three cohorts (SIRs [95% CIs] 3.72 [2.71-4.93], 5.97 [3.34-9.59], and 2.79 [1.82-4.02], respectively). In the bDMARD sub-cohort, no increase in SIRs was observed for other site-specific malignancies. In the All RA cohort, use of methotrexate, tacrolimus, glucocorticoids, non-steroidal anti-inflammatory drugs, and bDMARDs were not associated with the risk of overall malignancy; the hazard ratio (95% CI) was 1.36 (0.96-1.93) for bDMARD use. Increased disease activity was a time-dependent risk factor of overall malignancy with a hazard ratio (95% CI) of 1.35 (1.15-1.59).

Conclusions: The use of bDMARDs was not a time-dependent risk factor for malignancy.

Introduction: Clinical remission is the main target in the management of patients with rheumatoid arthritis (RA). However, several authors found synovitis in patients with RA in clinical remission at ultrasonography (US). Upadacitinib is a selective Janus kinase 1 inhibitor that achieved significantly higher remission rates than adalimumab and abatacept in patients with RA. Here we present the 24-week data of the UPAdacitinib Rheumatoid Arthritis REmission UltraSonography (UPARAREMUS) study.

Methods: This is a longitudinal multicenter observational study, enrolling bio-naïve and bio-inadequate responder patients affected by RA. The primary endpoint was the proportion of patients achieving both clinical and US remission at week 24. The proportion of patients achieving clinical remission with different composite indexes at week 12 and 24 was also evaluated. US of four target joints (wrists and second metacarpophalangeal bilaterally) was performed at baseline and weeks 12/24, and US remission was defined as the absence of power Doppler (PD) signal ≥ 2 in one target joint, or PD ≥ 1 in two target joints.

Results: After 12 weeks and 24 weeks, 40% and 63.6% of patients achieved US plus clinical remission. The following parameters were associated with US plus clinical remission: being bio-naïve and having a shorter disease duration, although at multivariate analysis significant odds ratio (OR) was found only for being bio-naïve.

Conclusions: UPARAREMUS is the first study evaluating the efficacy of upadacitinib in reaching both clinical and US remission in patients with RA. At 24 weeks, 63.6% of patients reached the primary endpoint, the only baseline associated parameter was being bio-naïve.

Introduction: Inflammatory bowel disease (IBD)-related arthritis is recognized as the most prevalent extraintestinal manifestation (EIM) of IBD. The objective of this study was to determine the prevalence and characteristics of undiagnosed IBD-related arthritis and to compare two screening questionnaires, DETection of Arthritis in Inflammatory boweL diseases (DETAIL) and IBd Identification of Spondyloarthritis Questionnaire (IBIS-q), for early disease detection.

Methods: Between April and October 2023, both the DETAIL and IBIS-q questionnaires were administered to consecutive IBD outpatients visiting the University Hospital of Udine, Italy. During routine gastroenterology evaluations, patients aged > 18 years with Crohn's disease (CD) or ulcerative colitis (UC) were requested to complete both questionnaires. Subsequently, all patients who completed the questionnaires underwent a blinded rheumatological evaluation within 2 weeks. Patients with a previous diagnosis of IBD-related SpA were then excluded.

Results: Overall, 203 patients were enrolled, of whom 26 were excluded because of a prior diagnosis of inflammatory arthritis. Among the remaining 177 patients, 10/177 (5.6%) received a new diagnosis of IBD-related arthritis. The median duration of symptoms before diagnosis was 4 (IQR 1.8-10.5) months. Imaging-confirmed enthesitis was the predominant pattern in 8 out 10 cases (80%, with 8 out 8 lacking concomitant peripheral arthritis), axial involvement in 1 out 10 cases (10%), and peripheral arthritis in 1 out 10 cases (10%). The DETAIL questionnaire exhibited higher specificity, but lower sensitivity compared to the IBIS-q, with a sensitivity of 40.0% (12.2-73.8) and specificity of 84.4% (78.0-89.6) versus a sensitivity of 70.0% (34.8-93.3) and specificity of 74.3% (66.9-80.7). Both questionnaires performed less effectively than in other studies.

Conclusion: This study highlights a significant proportion of undiagnosed IBD-related arthritis (5.6%). Enthesitis emerged as the predominant pattern of newly diagnosed arthritis in our cohort, likely due to the recent onset of symptoms. Our study underscores the importance of entheseal involvement in early IBD-related arthritis and the importance of incorporating entheseal involvement into screening questionnaires.