Rheumatology and Therapy最新文献

Introduction: There is limited prior literature comparing long-term treatment persistence between guselkumab and subcutaneous (SC) tumor necrosis factor inhibitors (TNFi) in biologic-naïve and biologic-experienced patients with active psoriatic arthritis (PsA). This study compared on-label persistence through 24 months between patients with active PsA newly initiating guselkumab or SC TNFi.

Methods: IQVIA PharMetrics^® Plus database was used to identify adults with active PsA initiating guselkumab or an SC TNFi (adalimumab or biosimilar, certolizumab pegol, etanercept or biosimilar, SC golimumab) between 07/14/2020 and 12/31/2022 (index date: first treatment claim for one of these medications). Patients were further stratified as biologic-naïve (no pre-index biologic disease-modifying antirheumatic drug [bDMARD] claim) or biologic-experienced (≥ 1 pre-index bDMARD claim). The guselkumab and SC TNFi cohorts were balanced using overlap propensity score weighting. Treatment persistence with on-label therapy (absence of dose modification or therapy exposure gap of twice the duration between consecutive administrations, i.e., 112 days for guselkumab or 56 days for SC TNFi) was estimated using weighted Kaplan-Meier analysis through 24 months. On-label persistence rates were compared between cohorts using weighted Cox proportional hazards models.

Results: In the guselkumab cohort (N = 804), 361 (44.9%) were biologic-naïve and 443 (55.1%) were biologic-experienced; in the SC TNFi cohort (N = 2490), 2171 (87.2%) were biologic-naïve and 319 (12.8%) were biologic-experienced. At 24 months post index, on-label persistence rates were 45.5% (guselkumab) versus 28.5% (SC TNFi; P < 0.001). Patients initiating guselkumab were 2.24 times more likely to be persistent with on-label therapy through 24 months than patients initiating an SC TNFi (hazard ratio [95% confidence interval] 2.24 [1.90, 2.64]; P < 0.001). Results were consistent among biologic-naïve (2.36 [1.88, 2.98]; P < 0.001) and biologic-experienced patients (1.86 [1.46, 2.37]; P < 0.001).

Conclusion: Patients with active PsA initiating guselkumab were significantly (approximately two times) more likely to remain persistent with on-label therapy through 24 months versus SC TNFi, overall and among biologic-naïve and biologic-experienced subgroups.

Introduction: Giant cell arteritis (GCA) is a chronic inflammatory vasculitis in large and medium-sized arteries. Glucocorticoids (GCs) remain the cornerstone of treatment but carry significant long-term adverse effects. Tocilizumab (TCZ), an interleukin (IL)-6 receptor inhibitor, has become a GC-sparing agent, yet optimal treatment duration remains uncertain.

Methods: This retrospective cohort study evaluated treatment patterns, clinical outcomes, and GC burden in patients (N = 121) with GCA treated at a specialized clinic in Montreal, Canada, between January 2017 and February 2025. Patients were stratified by initial treatment: GC only, GC + TCZ, and GC + other immunosuppressants (OIS). The primary endpoint was sustained remission at 12 months, defined by symptom resolution and normalization of inflammatory markers maintained for ≥ 6 months.

Results: Overall, two-thirds of patients (83, 68.6%) (95% confidence interval [CI] 60.3-76.9%) achieved sustained remission, with similar rates in GC only (35, 72.9%) and GC + TCZ (44, 69.8%) groups, but lower in the GC + OIS group (4, 40.0%). Most patients remained on GCs after 1 year, highlighting the difficulty of achieving steroid-free remission. Relapses occurred in nearly half of patients (58, 47.9%), with a median time to first relapse of 283.5 days (95% CI 206-326). Methotrexate showed limited GC-sparing efficacy, with several patients relapsing (6, 60%). TCZ-treated patients had the lowest cumulative GC exposure (mean 3431 mg (standard deviation [SD] = 1049) vs. 4690 mg (SD 969) in GC only), though a quarter of patients (16, 25.4%) relapsed after TCZ discontinuation.

Conclusion: The current 1-year TCZ treatment limit in Canada may be inadequate for long-term disease control. Adverse events were generally low, though hypertension, hyperglycemia, and infections were common. Two bowel perforations occurred in the TCZ group. These findings underscore the need for individualized, long-term treatment in GCA to minimize steroid exposure and maintain disease control. Future research should explore optimal therapy durations and support policy changes to expand access to steroid-sparing agents to improve long-term GCA outcomes.

Introduction: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A and was approved to treat patients with active psoriatic arthritis (PsA) in the European Union in 2023. This study compares the cost per responder (CPR) of bimekizumab against IL-17A (secukinumab), IL-12/23 (ustekinumab) and IL-23 (guselkumab and risankizumab) targeted therapies to treat patients with PsA in Spain.

Methods: The CPR was calculated by dividing the average annual drug cost per patient by the response rates for minimal disease activity (MDA) and American College of Rheumatology (ACR) 50 and ACR70 at week 52 in patients who were biological disease-modifying antirheumatic drug (bDMARD) naïve or who had experienced inadequate response or intolerance to tumour necrosis factor inhibitors (TNFi-IR). Response rates from four published matching-adjusted indirect comparisons (MAIC) were used. Spanish list prices and Royal Decree Law 8/2010 discounts were considered.

Results: In bDMARD-naïve patients, bimekizumab had a lower CPR for MDA and ACR70 versus all comparators except for secukinumab 150 mg, where the CPR for bimekizumab was higher for all three efficacy measures. The incremental CPR ranged between 17.2% (95% confidence interval [CI] - 26.1%, 50.6%) for ACR70 and 92.7% (95% CI 60.0%, 119.4%) for ACR50. The incremental CPR for ACR50 for bimekizumab compared to secukinumab 300 mg was also slightly higher (2.3% [95% CI - 12.5%, 14.3%]). In patients with TNFi-IR, bimekizumab was more cost-efficient than all comparators for the three response rate measures at week 52.

Conclusion: CPR analyses based on MAIC response rates at week 52 suggest that bimekizumab is more cost-efficient than IL-12/23 and IL-23 therapies, including ustekinumab, guselkumab and risankizumab, for treating PsA in Spain across both bDMARD-naïve patients and patients with TNFi-IR for all outcomes (MDA, ACR50/70). Compared to IL-17A (secukinumab), bimekizumab is consistently cost-efficient in patients with TNFi-IR for all outcomes and is cost-efficient in bDMARD-naïve patients versus those taking 300 mg regarding MDA and ACR70.

Introduction: Treat-to-target strategies for rheumatoid arthritis (RA) aim for remission or low disease activity (LDA) and improve long-term outcomes. The objective of this analysis is to report early achievement of remission or LDA at 3 months (M) in a real-world RA population and explore the long-term (2 years) outcomes of achieving early remission/LDA.

Methods: RA-BE-REAL is a 3-year, multinational, prospective, observational study of adult patients with RA. Patients initiated treatment with baricitinib (cohort A) or any biologic (b) disease-modifying anti-rheumatic drug (DMARD) or any other targeted synthetic (ts) (cohort B) for the first time. This analysis covers data from a European subpopulation of RA-BE-REAL. Effectiveness data at 3 months (early remission), and 24 months were presented descriptively. Logistic regression was used to determine associations between baseline characteristics and achievement of remission/LDA at 3 months and also associations between early remission/LDA and subsequent achievement of long-term remission/LDA at 24 months.

Results: At 3 months, high proportions of patients in both cohorts (cohort A: 59.4%, cohort B: 49.3%) reached remission or LDA. Patients achieving early remission or LDA had greater improvement in short- and long-term pain, functioning (HAQ-DI), and quality of life (EQ-5D-5L) than those who did not. Logistic regression found that previous experience with ≥ 2 previous b/tsDMARDs, higher Clinical Disease Activity Index (CDAI) scores, and lower EQ-5D-5L scores at baseline were negative predictors for the achievement of early remission or LDA. Furthermore, achievement of remission or LDA at 3 months was associated with remission or LDA at 24 months.

Conclusions: In a routine clinical practice population, achieving early remission/LDA was associated with maintained remission/LDA at 2 years as well as long-term improvement in pain, physical function, and quality of life in both cohorts.

Introduction: Osteoarthritis (OA) is associated with joint pain and disability, with increasing prevalence and economic burden. This study explored non-steroidal anti-inflammatory drugs (NSAID) treatment patterns, gastrointestinal (GI) complications and burden of disease in patients with OA based on Nordic registry data, with emphasis on individuals aged 60 or younger.

Methods: This non-interventional observational study analysed registry data from Norway, Finland, and Sweden. Adults with primary OA diagnosis in specialty care were matched 1:1 by age and sex with individuals of the general population. The primary outcome was NSAID treatment patterns, assessed by dispensations and daily defined doses (DDD) 1 year before and after diagnosis. Secondary outcomes included prevalence of comorbidities, the incidence of GI complications, sick leave, and joint replacements.

Results: The study included 189,553 patients with OA from Norway, 341,548 from Sweden, and 218,253 from Finland, 34.1% to 40.4% aged ≤ 60. About half of patients had NSAIDs dispensed before and after diagnosis, (Norway 56.6% and 48.6%; Sweden 50.1% and 44.0%; Finland 58.8% and 58.2%), compared to about one-fifth of the matches (Norway 19.1% and 18.5%; Sweden 12.7% and 12.2%; Finland 22.5% and 21.7%). NSAID use increased with age until approximately 55 years, then declined. After diagnosis, fewer patients had NSAID dispensations, but mean DDDs per prescription were generally higher. Secondary analyses showed a higher comorbidity burden, higher rates of GI complications, more sick leave days, and more joint replacements in patients with OA than in matched individuals.

Conclusion: Across Nordic countries, patients with OA had more NSAID dispensations, and GI complications were more prevalent compared to matched individuals. Notably, this was already evident in younger patients under the age of 60, underscoring the need for comprehensive GI risk assessment for every patient with OA. The substantial burden of OA was also evidenced by considerable numbers of sick leave days and joint replacements.

Introduction: The efficacy and safety of filgotinib (FIL) for the treatment of patients with rheumatoid arthritis (RA) have been evaluated in a number of randomized controlled trials. However, there is a scarcity of real-world studies evaluating the effectiveness, persistence, tolerability, and safety of FIL in everyday clinical practice. This study aimed to assess the effectiveness and retention rate of FIL in a real-world cohort of patients with RA.

Methods: A multicenter retrospective cohort study of patients with RA treated with FIL was conducted in 27 Italian tertiary referral rheumatology centers. The drug retention rate (DRR) was estimated by the Kaplan-Meier method, while multivariate Cox regression was used to detect potential factors affecting drug survival and persistence in therapy. Disease activity score (DAS28-CRP) was assessed at baseline and after 6 and 12 months.

Results: We enrolled 204 patients (80% female). The DRR of FIL was 90.2% (95% confidence interval (CI) 86-94.6%), 75.1% (95% CI 68.5-82.4%), and 64.7% (95% CI 56.3-74.3%) at months 6, 12, and 18, respectively. The DRR was negatively associated with the line of treatment and the presence of rheumatoid factor. Effectiveness was evaluated as DAS28-CRP response. At 6 months, DAS28-CRP remission was observed in 65 (36.1%) patients, and remission or low disease activity in 98 (54.4%). At 12 months, DAS28-CRP remission was observed in 64 (50.0%) patients, and remission or low disease activity in 81 (63.2%).

Conclusions: This analysis of real-world patients with RA demonstrated the effectiveness of FIL with a good DAS28-CRP response and high DRR at follow-up.

Introduction: Canakinumab was approved in Japan for the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) in 2018, following an open-label, single-arm phase III study performed in 19 Japanese patients with sJIA. Given this limited sample size, Japanese regulatory authorities required an all-case post-marketing surveillance study as part of the approval conditions, aiming to assess the long-term safety and effectiveness of canakinumab in Japanese patients with sJIA in clinical practice and characterise the clinical course of any cases of macrophage activation syndrome (MAS).

Methods: This was a multicentre, central registration, all-case, uncontrolled, open-label, special drug use investigation, including all patients who received canakinumab for the treatment of sJIA between 2 July 2018 and 20 December 2024. Patients were treated according to the investigators' routine clinical practice and observed for up to 104 weeks.

Results: The safety analysis population included 125 patients with a median duration of treatment (including interruptions) of 710.0 (range 1-729) days and median total number of doses of 25.0 (range 1-29). Adverse events (AEs) occurred in 91 out of 125 patients (72.8%), with the most common being relapse, worsening or exacerbation of Still's disease (24 patients, 19.2%), followed by upper respiratory tract inflammation (18 patients, 14.4%). Serious related AEs occurred in 22 patients (17.6%), with the most common being haemophagocytic lymphohistiocytosis (HLH; 5 patients, 4.0%). A total of ten MAS-related AEs were reported; all were cases of HLH and were considered serious, and all were resolved or were resolving at the time of reporting. Effectiveness outcomes, including glucocorticoid tapering, disease activity reduction and inflammatory marker normalisation, were durable through 2 years of treatment.

Conclusion: Canakinumab showed a favourable long-term safety profile and sustained effectiveness in Japanese patients with sJIA inadequately controlled by existing therapies. No new safety concerns emerged, and the safety profile was comparable to that observed in the earlier phase III study.

Introduction: The aim of this work was to evaluate the achievement of minimal clinically important improvement (MCII) in patient-reported outcomes (PROs) with guselkumab among participants with active psoriatic arthritis (PsA) and inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Methods: Post hoc analysis of phase 3b COSMOS study of participants with PsA and TNFi-IR randomized to guselkumab (N = 189) or placebo (N = 96) at week (W)0, W4 then every 8W through W44, with W16 (early escape) or W24 placebo-to-guselkumab transition. Time to MCII achievement (> 15-point) in patient global assessment of arthritis (PtGA Arthritis), PtGA Psoriasis, PtGA Arthritis + Psoriasis, and Patient Pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue, ≥ 4-point), Health Assessment Questionnaire-Disability Index (HAQ-DI, ≥ 0.35-point), 36-item Short-Form Health Survey physical component summary score (≥ 5-point), Dermatology Life Quality Index (DLQI, ≥ 5-point), and DLQI 0/1 with guselkumab vs. placebo was determined using Cox regression adjusting for baseline factors. Logistic regression compared MCII achievement rates between treatment groups. All p values are nominal.

Results: Time to MCII achievement across PROs through W24 was significantly faster with guselkumab vs. placebo (hazard ratio [HR] range 1.59 for PtGA Arthritis to 5.89 for DLQI), except for FACIT-Fatigue (HR 1.29, 95% confidence interval 0.93-1.81). Guselkumab treatment delivered significant improvements in PROs vs. placebo as early as W8 and through W24. Across all measures, odds of achieving MCII were higher with guselkumab vs. placebo at W8 (odds ratio [OR] range 1.43 for FACIT-Fatigue to 9.33 for DLQI) and W24 (OR range 3.12 for HAQ-DI to 19.42 for DLQI 0/1). MCII achievement rates for all PROs increased through W48 of guselkumab treatment, with consistent patterns following placebo-to-guselkumab transition.

Conclusions: In these hypothesis-generating analyses of a TNFi-IR PsA population, guselkumab demonstrated rapid (W8) MCII achievement in patient-reported skin and joint symptoms, and pain, followed by improvements in fatigue, functional status, and quality of life, with response rates increasing further through W48.

Trial registration: ClinicalTrials.gov identifier, NCT03796858.

Introduction: This post hoc analysis assessed tofacitinib and adalimumab efficacy and safety, stratified by baseline methotrexate (MTX) dose, in patients with rheumatoid arthritis (RA) in the Oral Rheumatoid Arthritis triaL (ORAL) Strategy study.

Methods: ORAL Strategy (NCT02187055) was a global, 1-year, phase 3b/4 study. Patients with RA and an inadequate response to MTX were randomized to tofacitinib 5 mg twice daily (BID), tofacitinib 5 mg BID plus MTX, or adalimumab 40 mg once every 2 weeks plus MTX, with MTX dosed per the last weekly dose pre-randomization. This post hoc analysis stratified patients by MTX dose in tertiles normalized by body mass index (BMI) and weight at baseline. Efficacy was assessed using American College of Rheumatology (ACR) 50 response rates at month 6 (primary endpoint); safety was assessed throughout. Efficacy and safety were analyzed descriptively.

Results: Of 1146 patients, 97 received MTX < 15 mg/week at baseline, 712 received 15-17.5 mg/week, and 337 received > 17.5 mg/week. In the tofacitinib and adalimumab combination therapy groups, similar ACR50 response rates at month 6 were observed across the baseline BMI-normalized MTX dose tertiles. This trend was also observed in the tofacitinib monotherapy group; however, the ACR50 response rates at month 6 were numerically higher with combination versus tofacitinib monotherapy, regardless of baseline BMI-normalized MTX dose tertile. Generally similar results were observed for the baseline weight-normalized MTX data. No clear trends across baseline BMI-normalized MTX dose tertiles were observed for safety outcomes.

Conclusions: In ORAL Strategy, tofacitinib efficacy was generally similar, and there were no clear safety trends regardless of baseline BMI-normalized MTX dose.

Trial registration: ClinicalTrials.gov identifier, NCT02187055.

Introduction: Advanced therapies (ATs) for ankylosing spondylitis (AS) vary in processes related to treatment administration. We hypothesized that treatment preferences for patients with AS vary based on AT experience and disease status.

Methods: This cross-sectional, mixed-methods study collected data from adults (aged ≥ 18 years) in the United States, United Kingdom, and Italy who had a confirmed AS diagnosis and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 and/or were currently taking AT. Burdensome aspects of AS and important AT administration attributes were identified in qualitative interviews with ten eligible patients. A cross-sectional online survey was also conducted, including a best-worst scaling (BWS) exercise with 12 treatment administration-related attributes and a series of six fixed-choice tasks, which presented two options varying only in mode and frequency of administration. Attribute relative importance was calculated from BWS data to sum to 100 across attributes. Frequencies and percentages were reported for fixed-choice tasks. Preferences from BWS data were compared by treatment/disease status (on AT/well controlled, on AT/not well controlled, not on AT/not well controlled) using one-way analysis of variance tests.

Results: In qualitative interviews, patients reported pain (70.0%) and symptom unpredictability (50.0%) as the most bothersome aspects of AS. Overall, 210 patients (mean age 44.0 years) completed the survey; 37.6% were currently on AT. Patients not on AT/not well controlled preferred oral dosing, and patients on AT/well controlled preferred once-monthly injection and avoiding office/clinic visits; attribute relative importance estimates for patients currently on AT/not well controlled typically fell midway between the other groups. Most patients currently on AT/well controlled (range 78.6-100.0%) preferred injectable over oral options. Many on AT/not well controlled preferred once-daily pill over once-monthly (30.8%) or twice-monthly (40.0%) injections; once-monthly injection was preferred over oral options (range 60.0-69.2%). Many patients not currently on AT/not well controlled (range 50.4-68.7%) preferred oral over injectable options.

Conclusions: Treatment preferences differed depending on whether AT was currently used and disease was well controlled. Findings enhance understanding of which patients may prefer different modes of AT administration.