Rheumatology and Therapy最新文献

Introduction: Bimekizumab (BKZ), a monoclonal antibody targeting interleukin (IL)-17A and IL-17F, has shown high efficacy in clinical trials. However, real-world data on its use in psoriatic arthritis (PsA) are limited. This study aimed to evaluate the effectiveness and safety of BKZ over 24 weeks in a real-world setting.

Methods: A retrospective, multicenter study was conducted at two Italian rheumatology centers, enrolling adult patients with PsA who initiated BKZ treatment between January 2023 and February 2025. Clinical data were collected at baseline, week 12, and week 24.

Results: Forty patients with PsA were included. Of these, 75% had failed at least two biologic and/or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) prior to BKZ and 25/40 (62.5%) had failed at least one IL-17A inhibitor (IL-17Ai). Among these 25 patients, 32% experienced a primary failure and 68% a secondary failure. The median baseline Disease Activity in Psoriatic Arthritis (DAPSA) score was 22.9 (17.5-27.2), decreasing to 6.0 (3.1-12.8) at week 24 (p < 0.001). By week 24, 72.5% achieved DAPSA low disease activity (LDA), and 25% achieved DAPSA remission. The median swollen joint count (SJC) decreased from 3.0 (0.8-5.3) to 0.0 (IQR 0.0-1.0), and median tender joint count (TJC) decreased from 4.5 (3.0-7.3) to 1.0 (0.0-2.0) (both p < 0.001). Pain visual analog scale (VAS) and Patient Global Assessment (PGA) improved significantly, from 7.0 (6.0-8.0) and 7.5 (6.5-8.0) at baseline to 2.0 (1.0-5.0) and 2.0 (1.0-4.5) at week 24 (both p < 0.001). Skin involvement also improved, with 51.5% achieving Psoriasis Area and Severity Index (PASI) 100 by week 24. The safety profile was favorable; 15% of patients developed mild oral candidiasis, none of which required treatment discontinuation.

Conclusion: BKZ demonstrated rapid and sustained improvements in PsA symptoms in a challenging real-world population, with a favorable safety profile.

Introduction: Psoriatic arthritis (PsA) is a complex disease in which remission or low disease activity is now an achievable target. This study aimed to evaluate "super-responders" (SR) among patients with PsA treated with advanced therapies and to explore possible clinical factors associated with the SR phenotype.

Methods: This is a retrospective analysis of a longitudinal cohort of patients diagnosed with PsA and treated with biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs), with at least 2 years of follow-up. SR were defined as patients achieving very low disease activity (VLDA) within 6 months of therapy initiation and maintaining VLDA for at least 2 years. Data from all clinical visits were reviewed to confirm response patterns. Patients who initiated treatment for PsA were included, regardless of prior biologic use for psoriasis. SR were compared with non-SR patients to identify clinical differences. Logistic regression was performed to evaluate features associated with SR.

Results: Among 177 evaluated patients, 29 (16.3%) were classified as SR. SR patients were more often of male sex, had significantly lower baseline pain visual analogue scale scores (p < 0.01), Patient Global Assessment score (p = 0.04), and shorter intervals between psoriasis and PsA diagnosis (p = 0.04). They were more frequently treated with interleukin-17 (IL-17) inhibitors at baseline (37.9% vs. 19.5%, p = 0.04) and had absence of cardiometabolic comorbidities. Logistic regression analysis confirmed associations between SR status and IL-17 treatment, absence of cardiometabolic comorbidities, and lower pain scores.

Conclusion: This study may identify a distinct subset of patients with PsA demonstrating rapid and sustained response to treatment. While promising, the clinical utility of the SR concept requires cautious interpretation, especially regarding potential treatment de-escalation. Further validation in multicenter prospective studies may be essential.

Introduction: Limited data are available on sex differences in the disease characteristics, burden and treatment outcomes of early psoriatic arthritis (PsA). The "Spondyloarthritis Italian Registry: Evidence from a National Pathway" (SIRENA) study is a prospective, observational, Italian study conducted in 23 Rheumatology sites on patients with recent diagnosis of spondyloarthritis and naïve to any disease-modifying antirheumatic drugs (DMARDs).

Methods: The study included 203 patients with early PsA, observed per clinical practice, who were studied regarding the influence of sex on the disease presentation and the likelihood of achieving minimal disease activity (MDA). Clinical and patient-reported outcome (PRO) measures were collected at both study entry and each follow-up visit until 24 months. Treatment was assigned by the treating rheumatologist based on standard clinical practice.

Results: At baseline, 87% of patients with PsA received systemic treatment, mainly with conventional (49%) or biological (25%) DMARDs. Twenty-three of 158 (15%) patients were already in MDA status at study entry: this percentage increased to 55% (n = 83/150) at 6 months and 75% (n = 73/97) at 24 months. MDA was more frequent in males at baseline (20.0% vs. 8.2% in females, p = 0.036) and throughout the study. Significant improvements in clinical measures and PROs were reported in both sexes at all follow-up visits, but PRO scores were significantly worse in females at baseline and at most endpoints. Increasing age, male sex, new PsA diagnosis, mono-/oligoarticular involvement, low (≤ 14) Disease Activity index for PSoriatic Arthritis (DAPSA) and low Health Assessment Questionnaire Disability Index (HAQ-DI) values showed potential associations with MDA achievement at 6 months in univariate analysis, but this was not significant in the multivariate model.

Conclusion: In patients with PsA naïve to DMARDs, sex considerably influences the clinical characteristics and outcomes.

Trial registration number: NCT03131661.

Introduction: Firsekibart, an anti-interleukin (IL)-1β monoclonal antibody, has demonstrated more sustained control of gout flares compared with compound betamethasone in previous clinical studies. This study evaluated the efficacy and safety of firsekibart versus etoricoxib for the treatment of frequent gout flares.

Methods: In this phase 2, randomized, open-label, active-controlled, multicenter study (NCT05936268), adults with gout according to American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) 2015 criteria experiencing frequent flares (≥ 2 flares within 12 months pre-screening) were randomized (1:1) to receive either a single subcutaneous injection of firsekibart 200 mg, or once-daily oral etoricoxib 120 mg administered until pain remission or treatment intolerance for up to 8 days. The primary endpoint was change from baseline in target joint pain intensity (0-100 mm visual analogue scale [VAS]) 72 h post-treatment. Non-inferiority (margin: 10 mm) was assessed first; if achieved, superiority was subsequently evaluated. Safety was also evaluated.

Results: Overall, 123 patients received firsekibart (n = 61) or etoricoxib (n = 62). Firsekibart was non-inferior and superior to etoricoxib in change from baseline in target joint pain VAS scores at 72 h post-treatment (difference: - 10.91 mm; 95% confidence interval [CI]: - 18.11, - 3.72). Treatment-emergent adverse events (TEAEs) occurred in 77.0% (n = 47) and 51.6% (n = 32) of patients receiving firsekibart and etoricoxib, respectively. The most common TEAE in both groups was hypertriglyceridemia. No TEAEs led to treatment discontinuation or study withdrawal, and no treatment-related serious adverse events (AEs) or deaths were reported.

Conclusions: Compared with etoricoxib, firsekibart provides superior target joint pain relief and is well-tolerated in patients with frequent gout flares.

Trial registration: ClinicalTrials.gov identifier: NCT05936268; date of registration: 7 July 2023.

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.