Rheumatology and Therapy最新文献

Introduction: The journey to axial spondyloarthritis (axSpA) diagnosis is often prolonged, and delayed diagnosis has been associated with poorer outcomes and increased healthcare costs. This study aimed to characterize the patient diagnostic journey in axSpA and associated healthcare resource utilization (HCRU) and costs in the US.

Methods: This observational, retrospective US MarketScan^® study utilized insurance claims data from the Commercial/Medicare Supplemental (January 2008-March 2023) and Medicaid (January 2008-December 2022) databases to assess the time to diagnosis in adult patients with back pain onset prior to a new axSpA diagnosis. This study evaluated the time to axSpA diagnosis from the earliest back pain diagnosis, and the diagnostic journey through the number of consultations with healthcare professionals (HCPs) for back pain, diagnostic tests, and imaging procedures. Back pain-related HCRU and costs were assessed, as well as pharmacy claims during this period.

Results: Of 97,469 patients included, 29.0% experienced time to diagnosis of ≥ 6 years, with a mean (standard deviation) of 4.5 (2.8) years to diagnosis. Prior to axSpA diagnosis, patients saw an average of 4.57 HCPs annually and had 20.7 back pain-related visits overall for back pain-related causes. Between the earliest back pain diagnosis and axSpA diagnosis, 55.9% of patients experienced > 10 back pain consultations, and patients underwent a range of diagnostic tests and imaging procedures. The median sum of non-capitated back pain-related costs up to axSpA diagnosis was $883.19 per patient per year, plus $1127.57 per patient per year for pharmacy prescriptions.

Conclusions: This study shows that diagnostic delay is a challenge for patients with axSpA in the US, despite numerous back pain consultations, specialist visits, and diagnostic tests. These findings highlight the urgent need for strategies to enhance recognition of axSpA and improve the patient diagnostic journey.

Connective tissue disease-related interstitial lung disease (CTD-ILD) refers to a range of pulmonary complications arising from connective tissue disorders, characterized by alveolar inflammation and interstitial fibrosis. Various factors, such as the specific type of connective tissue disease, infections, and hypoxemia, influence acute exacerbations of CTD-ILD. Treatment strategies typically include targeted interventions for precipitating factors, glucocorticoids, immunosuppressants, and supportive care. Glucocorticoids play a key role in managing acute exacerbations of CTD-ILD; however, the optimal dosing and duration of treatment remain uncertain. Immunosuppressants show potential therapeutic value, but further studies are needed to determine the most effective regimens for CTD-ILD patients. Supportive care, including respiratory support and oxygen therapy, is crucial for symptom relief and correction of hypoxia. Despite recent treatment advancements in China, significant challenges remain in optimizing outcomes and improving survival rates in CTD-ILD, highlighting the need for a comprehensive, individualized management approach for Chinese patients. Future research should focus on elucidating the pathogenesis of CTD-ILD, tailoring treatment strategies, and establishing standardized diagnostic and management protocols based on the Chinese population.

Introduction: Muscle and skin involvement are well defined in dermatomyositis but other symptoms contribute significantly to the disease burden and their treatment is not well characterized. This post hoc analysis of ProDERM assessed the effect of intravenous immunoglobulin (IVIg) treatment on other manifestations of dermatomyositis beyond muscular and cutaneous involvement.

Methods: ProDERM was a randomized, placebo-controlled study. For weeks 0-16, patients with dermatomyositis received 2.0 g/kg IVIg (Octagam, 10%) or placebo every 4 weeks. Eligible patients entered the open-label extension, where all received IVIg to week 40. Pulmonary, skeletal, constitutional, gastrointestinal, and cardiovascular disease activity was assessed using the myositis disease activity assessment tool, comprising a visual analog scale (VAS; 0-10 cm) and myositis intention-to-treat activity index.

Results: Of 95 patients enrolled, 47 received IVIg and 48 received placebo to week 16. At baseline, 37.9% of patients experienced pulmonary, 64.2% experienced skeletal, 76.8% experienced constitutional, 33.7% experienced gastrointestinal, and 15.8% experienced cardiovascular involvement (VAS > 0.5). Among these patients, for those on IVIg, the following mean VAS scores decreased from baseline to week 16: pulmonary (37.7%; P = 0.001), skeletal (52.6%; P < 0.001), constitutional (44.4%; P < 0.001), and gastrointestinal (49.2%; P = 0.005). No corresponding improvement was seen with placebo except for constitutional VAS. With IVIg, the proportions of patients with arthritis (36.2 to 17.8%; P = 0.01), arthralgia (68.1 to 0.0%; P < 0.001), and fatigue (68.1 to 3.3%; P = 0.008) decreased from baseline to week 16. In the combined cohort, the proportions of patients with dysphonia (20.0 to 8.1%; P = 0.04), arthralgia (66.3 to 39.8%; P < 0.001), weight loss (10.5 to 3.4%; P = 0.04), fatigue (75.8 to 50.0%; P < 0.001), and dysphagia (40.0 to 18.4%; P < 0.001) decreased from baseline to week 40.

Conclusion: IVIg was effective in treating pulmonary, skeletal, constitutional, and gastrointestinal manifestations of dermatomyositis. We advocate exploring IVIg as treatment for dermatomyositis, beyond muscle and skin manifestations.

Trial registration: ClinicalTrials. gov identifier, NCT02728752.

Objectives: Our objective was to evaluate the comparative effects of five Janus kinase inhibitors (JAKis) with ten interventions, comparing their impact on major adverse cardiovascular events (MACE) and thromboembolism events (TE) in patients with psoriatic arthritis (PsA) through network meta-analysis (NMA).

Methods: We conducted a search across four databases from inception to September 30, 2024. We also included studies comparing JAKis with placebo or TNFi in adults (≥ 18 years) with PsA. The primary outcomes were the incidence of MACE and TE. We used network meta-analysis with random effects to estimate summary risk ratios (RRs).

Results: Eleven studies met the eligibility criteria. Combined RCT and LTE data showed 23 MACE and 26 TE events, with incidence rates (IR) of 0.25 and 0.29 per 100 person-years for MACE and TE, respectively. Across all RCT data, there were 12 MACE and 8 TE events, with IRs of 0.62 and 0.41 per 100 person-years for MACE and TE, respectively. In eligible RCTs, tofacitinib (5 mg and 10 mg) and upadacitinib (30 mg) were associated with a lower risk of TE compared to placebo (GRADE certainty: moderate, moderate, and high, respectively). Compared to adalimumab, upadacitinib (15 mg and 30 mg) was associated with a decreased risk of MACE in RCT/LTE data (GRADE certainty: moderate and moderate, respectively).

Conclusions: Tofacitinib and upadacitinib are superior to placebo and comparable to adalimumab regarding MACE and TE risk, even with long-term exposure, which may be positively considered in PsA treatment. The cardiovascular safety of new investigational JAKis needs further validation.

Introduction: This study aimed to evaluate the influence of background conventional synthetic disease-modifying antirheumatic drug (csDMARD) use on efficacy and safety of deucravacitinib, a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in patients with psoriatic arthritis (PsA).

Methods: This phase 2, double-blind trial randomized 203 patients with active PsA 1:1:1 to oral placebo, deucravacitinib 6 mg, or deucravacitinib 12 mg once daily for 16 weeks. Patients had failed or were intolerant to ≥ 1 non-steroidal anti-inflammatory drug (NSAID), glucocorticoid, csDMARD and/or one tumour necrosis factor inhibitor. Patients were not stratified by csDMARD use and were allowed one background csDMARD if used for ≥ 3 months with stable dose for > 28 days prior to day 1; patients could not initiate new csDMARD treatment. This post hoc analysis evaluated the influence of background csDMARD use on efficacy outcomes, which included American College of Rheumatology (ACR) 20 responses and ACR scoring components; Psoriasis Area and Severity Index (PASI) scores; Psoriatic Arthritis Disease Activity Scores (PASDAS); and on safety measures.

Results: Baseline clinical characteristics and disease activity were generally similar among subgroups regardless of csDMARD use. At baseline, 65.0% of patients were taking background csDMARDs and among these 84.1% were taking methotrexate; percentages of methotrexate use were similar across groups. Similar ACR 20 response rates at week 16 were observed with deucravacitinib treatment in patients with vs without baseline csDMARD use compared with placebo (deucravacitinib 6 mg: 57.8% vs 44.0%; deucravacitinib 12 mg: 62.8% vs 62.5%; and placebo: 31.8% vs 31.8%, respectively). Similar responses with deucravacitinib compared with placebo, regardless of background csDMARD use, were observed in individual ACR components, PASI score, and PASDAS. The safety profile of deucravacitinib treatment was similar in patients with and without csDMARD use.

Conclusion: Background csDMARD use did not affect the efficacy or safety of deucravacitinib in this phase 2 PsA study. Graphical Abstract available for this article.

Trial registration: ClinicalTrials.gov ( https://clinicaltrials.gov ): NCT03881059.

Introduction: This guideline offers evidence-based recommendations for physicians and policymakers on managing axial spondyloarthritis (axSpA) in Saudi Arabia.

Methods: A panel of 14 experts in research methodology, rheumatology, family medicine, and clinical pharmacology in Saudi Arabia approved 45 questions related to the monitoring and treatment, pharmacological and non-pharmacological, of different subtypes of axSpA. We conducted a search of different databases, including PubMed, EMBASE, and the Cochrane Library, from 2010 to 2024 to identify systematic reviews, meta-analyses, and clinical studies related to the diagnosis and management of axSpA. To evaluate the certainty of the evidence and formulate recommendations, we employed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The expert panel voted electronically on each recommendation. A recommendation was finalized when over 70% of the voting panel agreed.

Results: We issued 31 evidence-based recommendations and seven statements based on the experts' opinions, which are grouped into nine categories. This guideline recommends initiating non-steroidal anti-inflammatory drugs (NSAIDs) as the first-line therapy for patients with symptomatic axSpA. If NSAIDs are ineffective, second-line treatments such as tumor necrosis factor inhibitors (TNFis), interleukin-17 inhibitors (IL-17is), or Janus kinase inhibitors (JAKis) should be considered. Localized glucocorticoid injections are suggested as supplementary therapy for cases of isolated sacroiliitis, enthesitis, or peripheral monoarthritis not responding adequately to the treatment options.

Conclusion: The Saudi clinical practice guidelines provide updated evidence-based recommendations for monitoring and treating adults with axSpA. These recommendations help guide the best practice for healthcare professionals in managing patients with axSpA in Saudi Arabia.

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.