Rheumatology and Therapy最新文献

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.

Introduction: Patients receiving the standard prophylaxis dose of colchicine for gout flares are at increased risk for developing toxicity if there are pre-existing renal impairment or drug-drug interactions. Guidelines recommend exercising caution, deferring dose adjustment to the clinician's discretion.

Methods: Pharmacokinetic study data for colchicine oral solution in healthy subjects was used to build a pharmacokinetic model. Using the derived pharmacokinetic disposition parameters from the best fit model and the derived parameters of clearance in patients with renal impairment, simulation of colchicine plasma levels to target 0.5-3 ng/mL with colchicine oral solution was undertaken for various dose levels in different degrees of renal impairment.

Results: With the standard colchicine 0.6 mg daily dose, plasma levels are expected to be therapeutic in patients with mild renal impairment (estimated glomerular filtration rate [eGFR] 60-89 mL/min/1.73 m²). However, with this same 0.6 mg daily dose, patients with moderate renal impairment (eGFR 30-59 mL/min/1.73 m²) and severe renal impairment (eGFR of 15-29 mL/min/1.73 m²) would have excursions up to 10% and 36%, respectively, above the maximum tolerated level. Administering a lower dose such as 0.3 mg daily by splitting the conventional 0.6 mg tablet or by administering 0.6 mg once every-other-day (QOD) in moderate renal impairment would result in plasma colchicine levels in subtherapeutic range (< 0.5 ng/mL) for 20-70% of the dosing interval.

Conclusion: Analysis of pharmacokinetic model data confirms that the majority of patients with renal impairment taking colchicine solid dosage formulations will be above or below therapeutic levels, exposing them to potential side effects. However, more precise dosing with colchicine oral solution of 0.48 mg (4 mL) or 0.5 mg tablet available in certain countries for moderate renal impairment and 0.3 mg (2.5 mL) for severe renal impairment are associated with optimal levels and safer for patients with renal impairment. No dosage adjustment is needed for patients with mild renal impairment.

Objective: To systematically evaluate the safety and feasibility of rapid rituximab (RTX) infusion protocols in patients with autoimmune rheumatic diseases.

Methods: A comprehensive literature review was conducted using PubMed, LILACS, and Scielo databases from 1965 to May 2024 without language restrictions. Studies reporting infusion reactions associated with accelerated RTX protocols (infusion over 90 to 120 min) in rheumatologic conditions were included. Infusion-related adverse events were assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (Grades 1-5). Key variables extracted included patient demographics, underlying diseases, RTX dosage, use of premedication, number of infusions, and frequency and severity of infusion reactions.

Results: Seven studies encompassing 538 patients aged 14-78 years were included. The patient cohort covered a spectrum of autoimmune rheumatic conditions, including systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, Sjögren's syndrome, systemic sclerosis, IgG4-related disease, and anti-synthetase syndrome. All studies implemented rapid RTX infusion protocols exclusively for the second and subsequent doses. Premedication with acetaminophen, diphenhydramine, and corticosteroids was routine in most studies. RTX dosage varied between 375 mg/m² and 1000 mg, administered in two infusions spaced two weeks apart. The incidence of infusion reactions ranged from 3 to 15%, predominantly of mild severity (Grades 1 and 2), with only six cases classified as Grade 3. No Grade 4 or 5 reactions were reported. Rapid infusion protocols consistently reduced the total time patients spent in infusion clinics.

Conclusion: Rapid infusion of RTX in patients with autoimmune rheumatic diseases appears to be a safe and efficient alternative to standard infusion protocols. The frequency and severity of infusion reactions were comparable to traditional infusion rates, with the added benefit of reduced clinic time. These findings support the broader implementation of rapid infusion protocols in rheumatology. However, larger prospective studies with standardized reporting of adverse events are necessary to validate these results and explore the feasibility of even shorter infusion durations, as seen in oncology.

Introduction: This study examined the benefit of belimumab as standard treatment in patients with systemic lupus erythematosus (SLE) treated without versus with immunosuppressants (IS) prior to belimumab initiation.

Methods: This retrospective cohort study (GSK Study 217537) used healthcare claims from the US Komodo Health Database from January 2015 to October 2023. Eligible adults had ≥ 1 inpatient or ≥ 2 outpatient SLE diagnosis codes, ≥ 1 belimumab claim (January 2017-October 2023; index date) and 24 months continuous data pre-index. Two cohorts were defined: those with ≥ 1 claim for non-IS SLE treatment (antimalarials, oral glucocorticoids [OGC] or biologics; non-IS cohort) or ≥ 1 claim for incident IS (IS cohort) within 12 months pre-index. Cohort comparability was assessed across the 12 months before non-IS/IS treatment, applying inverse probability of treatment weighting (IPTW) to adjust for confounding. Outcomes included OGC use, SLE flare rates and healthcare resource utilisation, compared using Cox, Poisson regression and logit models, respectively.

Results: Overall, 2190 and 2533 patients were included in IPTW-adjusted non-IS and IS cohorts, respectively. The non-IS cohort had a median (95% confidence interval [CI]) time to OGC discontinuation of 9.8 (8.2, 12.2) months versus 11.7 (10.5, 13.4) for the IS cohort, and a 30% higher likelihood of OGC discontinuation (hazard ratio [95% CI] 1.30 [1.11, 1.52]). The likelihood of OGC dose reduction and discontinuation or dose reduction alone was similar between cohorts. The non-IS versus IS cohort had a lower incidence rate ratio (IRR [95% CI]) of total (0.94 [0.92, 0.96]) and moderate (0.77 [0.74, 0.80]) SLE flares, with similar odds of SLE-related inpatient stays (odds ratio [95% CI] 1.12 [0.94, 1.34]) and emergency visits (1.02 [0.82, 1.27]).

Conclusion: In this large, retrospective, real-word study using IPTW adjustment, initiating belimumab without prior IS use was associated with OGC-sparing benefits and reduced incidence and severity of SLE flares.

Although the treatment landscape for systemic lupus erythematosus (SLE) has evolved in recent years, there is still a significant unmet need and many patients do not achieve key treatment goals, such as remission and low disease activity. Failure to reach these goals increases the risk of flare, organ damage accrual, and mortality in patients with SLE, and can have a significant impact on patient quality of life (QOL). While the importance of monitoring patients with SLE is highlighted across treatment recommendations, there is no clinical guidance on how to identify patients at risk of disease exacerbation and when to effectively initiate treatment reviews to improve their clinical outcomes. To address this, a panel of lupus experts have developed a clinical decision aid named the Lupus Check 5 Tool, which aims to identify patients in need of a treatment review through a simple five-question checklist. These questions cover a range of topics, including persistent glucocorticoid use, ongoing disease activity despite therapy, monitoring changes in laboratory values, flare frequency and severity, and the incorporation of the patient perspective and shared decision-making into clinical practice. Herein, we provide a detailed overview of the tool questions and the clinical evidence supporting their use to identify patients at risk of disease worsening. Use of the Lupus Check 5 Tool during each patient visit could facilitate timely alteration of therapy to help reduce disease activity, improve QOL, and work toward the long-term goals of remission and low disease activity.

Introduction: Pegloticase rapidly reduces serum urate (SU) in uncontrolled gout. This preliminary retrospective analysis of a large US rheumatology database examined post-pegloticase use and SU-lowering efficacy of oral urate-lowering therapy (ULT; allopurinol, febuxostat, probenecid).

Methods: Patients in the United Rheumatology (UR)-NICE data repository with first pegloticase code (J2507) in 2012-2022 and data for ≥ 60 days following last infusion were included. Post-pegloticase oral ULT efficacy was defined as SU < 6 mg/dL after oral ULT initiation and examined by shorter (< 12 infusions) and longer (≥ 12 infusions) pegloticase course and by time to post-pegloticase oral ULT start.

Results: A total of 211 patients (77.3% male; 62.7 ± 12.8 years, body mass index 32.9 ± 7.2 kg/m², estimated glomerular filtration rate 66.0 ± 24.7 ml/min/1.73 m²) with gout [74.4% tophaceous, SU 7.9 ± 2.5 mg/dL (n = 148)] were included; 66.8% received pre-pegloticase oral ULT (48.8% allopurinol, 32.2% febuxostat, and/or 12.3% probenecid). Patients received 12.3 ± 12.6 pegloticase infusions [median 9; 88 (42%) ≥ 12 infusions; 2.3 ± 2.0 weeks between infusions], with 115 patients (54.5%) beginning oral ULT after pegloticase discontinuation (67.0% allopurinol, 43.5% febuxostat, and/or 16.5% probenecid) most-often (66.1%) ≤ 30 days of last infusion. More patients who received ≥ 12 infusions than < 12 infusions had SU < 6 mg/dL with post-pegloticase oral ULT use [first post-ULT SU < 6 mg/dL, 78.4% vs. 36.2%; SU 4.7 ± 3.0 (n = 37) vs. 7.4 ± 2.9 (n = 47) mg/dL].

Conclusions: In this uncontrolled gout population, approximately two-thirds of patients began oral ULT within 30 days after their last pegloticase infusion. Those with longer pegloticase course more often had oral ULT efficacy, perhaps because of greater urate burden depletion, suggesting oral ULTs may be effective after successful pegloticase therapy. Further studies to understand any influence of urate burden on oral ULT efficacy are warranted.