Rheumatology and Therapy最新文献

Introduction: Tumor necrosis factor inhibitors (TNFi) may have insufficient efficacy in 40% of patients with axial spondyloarthritis (axSpA), leading to continued pain. We aimed to compare real-world effectiveness of switching from an initial TNFi to upadacitinib (TNFi-UPA), another TNFi (TNFi-TNFi), or an interleukin-17 inhibitor (TNFi-IL-17i) in patients with axSpA.

Methods: Data were drawn from the Adelphi Real World Spondyloarthritis Disease Specific Programme™, a cross-sectional survey of physicians and their patients with axSpA in France, Germany, Italy, Spain, the UK, and the USA from March-November 2021 and June 2023-June 2024. Patients who switched treatment from an initial TNFi were stratified by subsequent therapy: TNFi-UPA, TNFi-TNFi, or TNFi-IL-17i. Physician-reported clinical outcomes including pain (rated 0-10) and number of joints affected by inflammation or stiffness (from 0 to 68) were evaluated ≥ 3 months from treatment switch. Differences in characteristics were adjusted at the point of switch via inverse-probability-weighted regression adjustment to compare outcomes in separate analyses by subsequent class of therapy: TNFi-UPA versus TNFi-TNFi or TNFi-UPA versus TNFi-IL-17i.

Results: Overall, 310 physicians provided data for 557 patients; 108 were TNFi-UPA, 271 TNFi-TNFi, and 178 TNFi-IL-17i. A higher proportion of patients in the TNFi-UPA group achieved a ≥ 2 point and ≥ 33% reduction in pain than those in the TNFi-IL-17i (97.6% vs 86.4%; p = 0.002) or TNFi-TNFi (100.0% vs 80.1%; p < 0.001) groups. More patients achieved ≥ 50% reduction in pain in the TNFi-UPA group compared to TNFi-IL-17i (90.9% vs 74.0%; p = 0.004) or TNFi-TNFi (96.3% vs 72.3%; p = 0.024). More patients in the TNFi-UPA group had no affected joints than TNFi-IL-17i (93.1% vs 72.6%; p = 0.002) or TNFi-TNFi patients (100.0% vs 79.2%; p < 0.001).

Conclusion: This real-world study demonstrated that more patients who switched from TNFi to UPA had improvements in pain and affected joints compared to those who switched to a second TNFi or IL-17i.

Introduction: Giant cell arteritis (GCA) typically requires long-term treatment with glucocorticoids (GC). However, prolonged use of GCs has been associated with increased risk of GC-related side effects and adverse events. This study assessed the burden of GCs in GCA across the comprehensive framework of 39 adverse events, across 11 clinical categories, and side effects commonly associated with GC use (GRAEs).

Methods: This retrospective, observational study leveraged Merative MarketScan® databases (01/01/2009-12/31/2020), identified patient newly diagnosed with GCA, and assessed GC use, GRAE events, healthcare resource utilization (HCRU), and costs for ≥ 12 months up to 60 months post GC initiation. Eligible patients were ≥ 50 years old, with continuous plan enrollment for ≥ 12 months post-index GCA diagnosis (GCA + GC cohort) and were newly treated with GCs. Patients in the GCA + GC cohort were compared with a control cohort with no GCA and no GC (CC1) and a second control cohort of no GCA (CC2).

Results: Patients with GCA + GC versus control cohorts had significantly (p < 0.001) higher occurrence of 38 of 39 GRAEs assessed, with absolute differences ranging from 3% among musculoskeletal events to 20% among bone-related events. Patients in the GCA + GC cohort had greater HCRU compared with both control cohorts; compared to CC1, patients with GCA + GC had two times higher rates of hospitalization, and greater mean all-cause medical costs ($37,936 ± $65,325 vs $12,498 ± $48,793; p < 0.001) and results were similar when compared to CC2. Accounting for GRAEs, GCA-related costs more than doubled ($6337 ± $14,460 vs $13,995 ± $30,987).

Conclusion: Patients newly diagnosed with GCA and newly treated with GCs experience significantly higher rates of GRAEs in every category and two-fold higher healthcare costs. These data reflect the medical and financial burden for patients with GCA receiving GCs and establishes a comprehensive framework for assessing GC-related conditions for inflammatory diagnoses.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation and pain. Baricitinib, a targeted JAK inhibitor indicated for moderate to severe RA, has shown efficacy and safety, but real-world data on effectiveness and discontinuation rates are limited. This study aimed to report time to discontinuation, effectiveness, and patient-reported outcomes in patients initiating baricitinib or other biologic/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) in the Spanish clinical practice.

Methods: The subgroup from 11 Spanish hospitals in the multinational prospective RA-BE-REAL study was analysed. Patients treated for the first time with baricitinib or other b/tsDMARD were included. The primary objective was time to all-cause discontinuation of treatment at 24 months. Secondary objectives included assessing baseline characteristics, treatment patterns, and effectiveness on disease activity, health-related quality of life (HRQoL) and pain. Statistical analyses were descriptive in nature.

Results: Eighty patients initiating baricitinib (cohort A, n = 31) or any b/tsDMARD (cohort B, n = 49) were included. Most patients were women, with mean age 62.6 and 57.0 years, respectively; 58.1% in cohort A and 40.8% in cohort B had prior b/tsDMARD treatment. After 24 months, 61.3% and 44.9% continued their initial treatment, respectively. Main reason for discontinuation was secondary loss of response (19.4% and 26.5%, respectively). After 3 months, both cohorts showed improvements in disease activity, swollen and tender joint counts, physician and patient global assessments, disability, pain, and HRQoL. This trend to improvement was maintained for up to 24 months, suggesting a rapid and sustained response. At 24 months, 46.4% and 29.3% achieved low disease activity; 10.7% and 26.8% achieved remission, respectively.

Conclusion: The study suggests that baricitinib, despite being used in an older and more treatment-experienced cohort, shows comparable effectiveness and a trend towards lower discontinuation rates for up to 24 months, reinforcing its potential as a treatment option.

This Summary of Research summarises results from the BE OPTIMAL (NCT03895203) and BE COMPLETE (NCT03896581) studies and their open-label extension, BE VITAL (NCT04009499). These phase 3 studies looked at how well bimekizumab treatment worked in patients with psoriatic arthritis, and the safety of bimekizumab treatment, over the long term. Two patient groups were included in these studies: patients who had not previously been treated with biologic disease-modifying antirheumatic drugs (bDMARD-naïve; BE OPTIMAL) and patients who had a poor response or were intolerant to tumour necrosis factor (TNF) inhibitors (BE COMPLETE). These studies showed that the beneficial effects of bimekizumab treatment on patients' symptoms reported at year 1 of treatment were sustained up to 2 years, regardless of whether patients were bDMARD-naïve or had previously had a poor response or intolerance to TNF inhibitors. Bimekizumab was well tolerated up to 2 years. The data from this study may help clinicians and patients when they are making shared decisions on treatment options for psoriatic arthritis.

Introduction: The prevalence of knee osteoarthritis (OA) is rising worldwide, leading to disability and a reduced quality of life, particularly in elderly patients. While there are several treatment options, there is little consensus in the scientific community over which methods are most effective. Viscosupplementation with hyaluronic acid (HA) has been found to reduce pain in patients with knee OA over a period of up to 6 months, with little to no side effects. The aim of this prospective open-label, uncontrolled, observational, single-site study was to assess the efficacy and safety of a single hybrid HA injection over a period of 6 months in subpopulations of patients with low to severe symptomatic knee OA in everyday clinical practice.

Methods: Fifty patients who met the inclusion criteria participated in the study. A single intra-articular ultrasound-guided injection of hybrid HA (Sinovial®) was administered. Patients submitted Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaires at 28, 42, 84, and 168 days post-treatment.

Results: VAS scores measured at rest and when walking indicate an improvement during follow-up, particularly at 28 and 42 days, compared to baseline. Similarly, the most notable improvement of the WOMAC score was observed within the first 42 days after injection. While decrease in pain and joint function improvement were not as pronounced at the end of follow-up, they were still statistically better than at baseline. Overall patient satisfaction was high.

Conclusion: Treatment with a single injection of hybrid HA was demonstrated to be safe and effective in patients with varying degrees of knee OA. Patients with medial knee OA responded better to treatment than patients with patellofemoral OA, which provides information on which types of patients are best suited to this intervention.

Trial registration: ClinicalTrials.gov identifier, NCT06652893. Retrospectively registered October 10, 2024.

Introduction: Studies evaluating the long-term comparative efficacy between biologic therapies for psoriatic arthritis (PsA) are scarce. Two biologic therapies, guselkumab and secukinumab, were evaluated up to 52 weeks in a mixed patient population (biologic-naïve and biologic-experienced patients).

Methods: An unanchored matching-adjusted indirect comparison (MAIC) was conducted to compare guselkumab 100 mg every 8 weeks (Q8W) and every 4 weeks (Q4W) versus secukinumab 150 mg Q4W and 300 mg Q4W on American College of Rheumatology (ACR) and Psoriasis Area and Severity Index (PASI) responses from weeks 4 through 52 using pooled individual patient-level data from guselkumab trials (COSMOS, DISCOVER-1 and -2) and pooled summary-level data from secukinumab trials (FUTURE 2, 3, 4, and 5). For the primary analysis, patients from the guselkumab trials were re-weighted on six clinically relevant baseline characteristics to match those in the secukinumab trials. Additional characteristics were included as a sensitivity analysis. A scenario analysis was conducted in a biologic-naïve patient population only.

Results: For the mixed population, both guselkumab doses initially had numerically or significantly lower ACR 20 responses than both secukinumab doses prior to weeks 12-20; however, from weeks 12-24 onward, ACR 20 responses became numerically or significantly higher for guselkumab. For PASI 90 responses, both guselkumab doses showed significantly higher responses than both secukinumab doses at weeks 24 and 52. Notably, at 52 weeks, ACR 20 and PASI 90 responses for both doses of guselkumab were numerically or significantly higher than both doses of secukinumab. Results from the sensitivity and scenario analyses were similar to the primary analysis.

Conclusions: While the IL-17A inhibitor secukinumab may demonstrate more rapid and greater efficacy before weeks 12-20, both doses of guselkumab provide similar or greater efficacy on joint and skin outcomes compared to both doses of secukinumab from week 24 onward. This study provides valuable insights for treatment decisions when considering the chronic nature of PsA.

Introduction: Although the efficacy of tumor necrosis factor inhibitors (TNFi) is reduced in patients with rheumatoid factor (RF)-high rheumatoid arthritis (RA), certolizumab pegol (CZP), lacking the Fc portion, may not be affected. This study aimed to compare CZP with Fc-containing TNFi and investigate whether RF levels affect the efficacy of CZP in patients with RA.

Methods: This multicenter retrospective study involved patients with RA (n = 1010) who received TNFi with concomitant methotrexate (MTX). Patients were categorized by baseline RF quartiles. The primary endpoint was the Simplified Disease Activity Index (SDAI) remission rates at 26 weeks for patients treated with CZP and those receiving Fc-containing TNFi. The secondary endpoint compared the efficacy of CZP and adalimumab (ADA) in each RF quartile using propensity score-based inverse probability of treatment weighting (PS-IPTW).

Results: In the overall cohort, the SDAI remission rate was the lowest in Q4 (RF ≥ 136.45 IU/mL). In Q4, multivariable logistic regression analysis showed that only the introduction of CZP was significantly associated with remission at 26 weeks. The Fc-containing TNFi group had significantly lower SDAI remission rates in Q4 compared with Q1-Q3. Conversely, the SDAI remission rates were similar between the two groups treated with CZP. After PS-IPTW adjustment in Q4, CZP-treated patients showed a significantly lower SDAI and higher remission rate (36.6%) compared with the ADA-treated patients (24.5%) (p = 0.0172). No significant differences in SDAI remission rates were observed between the two groups in Q1-Q3.

Conclusion: CZP may be more effective than Fc‑containing TNFi in patients with RA and high RF levels.

This summary-of-research article presents the findings of a post hoc analysis comparing immunogenicity across the VOLTAIRE trials program, originally published in BMJ Open. Adalimumab-adbm (Cyltezo^®) is approved by the US Food and Drug Administration as an interchangeable biosimilar to the adalimumab reference product (RP; Humira^®). In this analysis of immunogenicity in patients who participated in VOLTAIRE-RA (NCT021372260), VOLTAIRE-CD (NCT02871635), and VOLTAIRE-PsO (NCT02850965), immune response was assessed in patients of each biosimilar and RP treatment arm at various time points, and further stratified by patient sex. Across VOLTAIRE trials, the incidence of immunogenicity parameters had similar trajectories and were highest in VOLTAIRE-PsO, followed by VOLTAIRE-CD and VOLTAIRE-RA, highlighting the effects of differences in patient populations and background medications on immune response for each indication. The same trend was observed in subgroup analyses by patient sex. These analyses show supporting evidence of the biosimilarity of adalimumab-adbm with adalimumab RP in adult patients with rheumatoid arthritis, Crohn's disease, and plaque psoriasis.Trial Registrations: VOLTAIRE-RA, NCT021372260; VOLTAIRE-CD, NCT02871635; VOLTAIRE-PsO, NCT02850965.

Introduction: Ixekizumab, an interleukin 17A inhibitor, improved the Assessment of SpondyloArthritis international Society 40 (ASAS40) response rates irrespective of baseline inflammation in international populations with radiographic axial spondyloarthritis (r-axSpA). We investigated the association of baseline inflammation (measured by serum C-reactive protein [CRP] levels) with ixekizumab efficacy in Chinese patients with r-axSpA.

Methods: This was a subgroup analysis of a Chinese phase 3 study. Adults with r-axSpA who were biologic-naïve, or tumor necrosis factor inhibitor-experienced with baseline CRP > 5 mg/l, were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W) or placebo, for 16 weeks. The following endpoints were analyzed by normal (≤ 5 mg/l) or elevated (> 5 mg/l) baseline CRP levels: ASAS40; Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50); Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1; ASDAS clinically important improvement (CII; change from baseline ≥ 1.1); ASDAS major improvement (MI; change from baseline ≥ 2.0 or achievement of lowest possible score); Bath Ankylosing Spondylitis Metrology Index (BASMI) linear score; Bath Ankylosing Spondylitis Functional Index (BASFI); Short Form-36 Physical Component Score (SF-36 PCS).

Results: A total of 147 patients were randomized. At week 16, the ASAS40 response rate was greater with IXEQ4W versus placebo in the normal (50.0% vs. 15.0%; p < 0.05) and elevated (29.5% vs. 5.7%; p < 0.01) CRP subgroups. Significant improvements in BASDAI50 response rate, ASDAS < 2.1, and ASDAS CII with IXEQ4W versus placebo were observed in both subgroups (normal CRP: p < 0.05, p < 0.01, and p < 0.05, respectively; elevated CRP: p < 0.01, p < 0.001, and p < 0.001, respectively); IXEQ4W significantly improved ASDAS MI in the elevated CRP subgroup (p < 0.001). IXEQ4W significantly improved linear BASMI and BASFI scores in the normal CRP subgroup (p < 0.001 and p < 0.01, respectively), while SF-36 PCS improved in both subgroups (both p < 0.05).

Conclusions: Ixekizumab showed efficacy in Chinese patients with r-axSpA, irrespective of baseline CRP levels, consistent with results in international populations with r-axSpA.

Trial registration: ClinicalTrials.gov identifier, NCT04285229.

Introduction: This study aimed to describe outpatient visit volume in a subspecialty clinic before, during, and after COVID lockdown.

Methods: We assessed monthly in-person and virtual visit volume (telephone-only or video) of 257 patients with rheumatoid arthritis (RA) at one academic center before, during, and post COVID lockdown, November 2018 to September 2021. The primary outcome was monthly visit volume to a rheumatologist. Visit volume, visit type (in-person vs. virtual), and annual visit frequency per patient were assessed. Piecewise Poisson regression models were constructed to examine visit volume trends. Predictors of patient's visit volume before and after the lockdown were examined using multivariable linear regression.

Results: Median patient age was 58 years; 84% were female; 82% used any disease-modifying anti-rheumatic drug (DMARD), and 62% used a targeted or biologic DMARD. Visit volume was stable 18 months prior to the COVID pandemic [slope 1.00 (95% confidence interval (CI) 0.99-1.01)] and increased at a rate of 2% per month post-lockdown [1.02 (95% CI 1.01-1.03)]. In-person visit volume was greatly reduced during the lockdown, with 61% virtual (51% video, 10% telephone). In the 18 months after lockdown, visit volume rebounded to pre-pandemic levels and continued to increase, with 11% virtual. Older age, serologic status, use of combination DMARDs, and non-steroidal anti-inflammatory drug (NSAID) use predicted greater visit volume during the pre-lockdown period. No variables predicted visit volume post-lockdown.

Conclusion: While COVID caused a huge disruption in rheumatology practice, visit volume for RA rebounded in one American academic center, with an increasing slope in visit volume after lockdown.