Rheumatology and Therapy最新文献

Introduction: This post hoc analysis of VOLTAIRE-RA compared patient-reported outcomes, including health-related quality of life (HRQoL), in patients with rheumatoid arthritis (RA) before and after treatment with biosimilar adalimumab-adbm or adalimumab reference product.

Methods: HRQoL was assessed by 36-Item Short Form Survey (SF-36) Physical and Mental Component Summary (PCS and MCS, respectively) and domain scores at baseline and weeks 12/24. Results were considered clinically meaningful if improvements were greater than or equal to minimum clinically important differences (MCIDs) of 2.5 for PCS and MCS and 5.0 for domain scores. Comparisons with age- and sex-matched norms and treatment-associated changes in domain scores from baseline were quantified using spydergrams and the health utility SF-6D measure. All comparisons between treatment groups were descriptive in nature.

Results: No differences in PCS scores were reported between treatment groups at baseline or weeks 12/24. MCS scores slightly favored the reference product group at baseline, and differences in scores at weeks 12/24 generally reflected those differences. Improvements in PCS scores greater than or equal to MCID at weeks 12/24 were reported by over 65% of patients in both treatment groups, while over 56% experienced improvements in MCS scores greater than or equal to MCID at weeks 12/24. Similar proportions receiving reference product and adalimumab-adbm reported scores greater than or equal to US age- and sex-matched normative values at week 24: 14-39% versus 15-36%, respectively, compared with baseline (1-17%).

Conclusion: In patients with moderate to severely active RA, adalimumab-adbm and adalimumab reference product were both associated with clinically meaningful improvements in SF-36 PCS, MCS, and domain scores that were highly similar at weeks 12/24. The high proportion of patients reporting scores greater than or equal to normative values in both treatment groups is notable, as this represents a treatment goal that was difficult to achieve in earlier RA trials. Video abstract available for this article.

Trial registration: VOLTAIRE-RA (ClinicalTrials.gov number, NCT02137226; EudraCT number, 2012-002945-40). Video abstract (MP4 29755 KB).

Introduction: Some retrospective data sources, such as electronic health records in the USA, report composite outcome measures not fully validated in psoriatic arthritis (PsA). However, they often contain global assessments, such as a Physician Global Assessment (PhGA) and Patient Global Assessment (PatGA), along with patient-reported pain scores, which individually are considered validated in PsA. This research described the performance characteristics of a 3-item global assessment and pain (GAP) composite endpoint using data from the ixekizumab phase 3 PsA clinical trial program.

Methods: Discrimination of GAP was assessed by comparing placebo to active treatment arms. The magnitude of treatment effect and responsiveness were compared to Disease Activity Index for PsA (DAPSA), clinical DAPSA, DAPSA28, and Psoriatic Arthritis Disease Activity Score (PASDAS) using effect size (ES) and standardized response mean (SRM), respectively. Construct validity was evaluated through correlation among the composite endpoints, and with other physician- and patient-reported outcomes. Change in GAP was compared in patients who reached low disease activity (LDA) levels based on DAPSA, cDAPSA, and PASDAS vs those who did not.

Results: GAP discriminated between active treatment and placebo with statistically significant separation as early as week 1. The largest ES/SRM was seen with GAP (2.29/1.74) and PASDAS (2.47/1.68). GAP had the strongest correlation with PASDAS (0.81-0.92) and showed moderate correlations with patient-assessed physical function, low correlations with physician-assessed skin and nail psoriasis, and low to moderate correlation with physician-assessed enthesitis. A significantly greater improvement in GAP was seen in the groups achieving LDA states compared to those not (p < 0.001).

Conclusion: The GAP composite, an abbreviated endpoint comprising measures common in electronic health records, has promising performance characteristics and could be used to address important clinical questions regarding outcomes and impact of PsA in existing datasets. CLINTRIALS.

Gov identifier: NCT01695239; NCT02349295.

Introduction: Racial disparities in disease activity, clinical outcomes, and treatment survival persist despite advancements in rheumatoid arthritis (RA) therapies and clinical management. In this post hoc analysis of pooled data from the tofacitinib global clinical program, we evaluated the impact of race on the efficacy and safety of tofacitinib in patients with RA.

Methods: Data were pooled from 15 phase 2-3b/4 studies of patients with RA treated with tofacitinib 5 or 10 mg twice daily, adalimumab, or placebo. Outcomes were stratified by self-reported patient race (White/Black/Asian/Other). Efficacy outcomes to month 12 included: American College of Rheumatology (ACR)20/50/70 responses, Clinical Disease Activity Index (CDAI)/Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] low disease activity (LDA) rates, least squares (LS) mean change from baseline (∆) in CDAI, DAS28-4 (ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), and Pain [Visual Analog Scale (VAS)]. Odds ratios (ORs; 95% CI) versus placebo, and placebo-adjusted ∆LS means were calculated for active treatments using logistic regression model and mixed-effect model of repeated measurements, respectively. Safety outcomes were assessed throughout.

Results: A total of 6355 patients were included (White, 4145; Black, 213; Asian, 1348; Other, 649). For tofacitinib-treated patients, ORs for ACR20/50/70 responses and CDAI/DAS28-4(ESR) LDA rates through month 3 were generally numerically higher for White/Asian/Other versus Black patients. Across active treatments, trends toward higher placebo-adjusted improvements from baseline in CDAI, DAS28-4 (ESR), HAQ-DI, and Pain (VAS) were observed in Asian/Other versus White/Black patients. Numerically higher placebo responses in Black versus White/Asian/Other patients were generally observed across outcomes through month 12. Safety outcomes were mostly similar across treatment/racial groups.

Conclusions: In patients with RA, tofacitinib was efficacious across racial groups with similar safety outcomes; observed racial differences potentially reflect patient demographics or regional practice disparities.

Trial registration numbers: ClinicalTrials.gov identifiers: NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01359150; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055.

Introduction: The Patient Acceptable Symptoms State (PASS) is a validated instrument that is used to assess whether a patient with psoriatic arthritis (PsA) accepts her/his disease status by asking them a simple question: "Think about all the ways your PsA has affected you during the last 48 h. If you were to remain in the next few months as you were during the last 48 h, would this be acceptable to you?" The aim of the present study was to explore any PASS differences in patients with PsA based on sex by looking at the corresponding thresholds of Disease Activity for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Impact of the Disease-12 (PsAID-12) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) in female and male patients.

Methods: This was a cross-sectional study that included two PsA cohorts. To identify the DAPSA, PsAID and HAQ-DI thresholds that differentiated patients who reported "yes" in response to the PASS question from those who reported "no," we used the receiver operating characteristic curves both for the female and male sexes. Moreover, Cohen's kappa test was used to determine the agreement of a PASS "yes" with DAPSA ≤ 14, PsAID ≤ 4 and HAQ-DI ≤ 0.5.

Results: Three-hundred ten patients were considered for the study. The DAPSA, PsAID-12 and HAQ-DI thresholds that differentiated PASS "yes" patients from PASS "no" patients were 11.7, 1.85 and 0.625 in male patients and 13.3, 3.85 and 0.750 in female patients, respectively. A PASS "yes" and DAPSA ≤ 14 showed moderate agreement in males (kappa = 0.56) and good agreement in females (kappa = 0.80); the agreement between a PASS "yes" and PsAID ≤ 4 and between a PASS "yes" and HAQ-DI ≤ 0.5 was higher in female patients (moderate).

Conclusion: Female patients accept their disease at higher DAPSA, PsAID and HAQ-DI values than male patients do. The clinical meaning of this could be that a female patient generally has a greater global disease acceptance inclination. Therefore, this study further supports the concept that sex differences are present in patients with PsA.

Introduction: In ORAL Surveillance, incidence rates (IRs) of major adverse cardiovascular events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) in cardiovascular (CV)-risk-enriched patients with rheumatoid arthritis (RA) were numerically greater with tofacitinib in North America versus the rest of the world, due to underlying risk factors. Here, we evaluated the safety and efficacy of tofacitinib versus tumor necrosis factor inhibitors (TNFi) among patients with RA across geographical regions.

Methods: Patients with RA in ORAL Surveillance (NCT02092467), who were aged ≥ 50 years with ≥ 1 additional CV risk factor, received tofacitinib 5 or 10 mg twice daily or TNFi; 45.9% were from either Poland or North America. This post hoc analysis stratified patients by region (Poland, North America, Other countries). Efficacy endpoints included Clinical Disease Activity Index, Disease Activity Score in 28 joints, with C-reactive protein (DAS28-4[CRP]), and Health Assessment Questionnaire-Disability Index (HAQ-DI). IRs and hazard ratios for adverse events were reported.

Results: Of 4362 patients (Poland, N = 759; North America, N = 1243; Other countries, N = 2360), more patients from North America versus Poland/Other countries had CV risk factors such as body mass index ≥ 30 kg/m² and history of diabetes/hypertension; however, more patients from Poland versus other regions were ever smokers and more patients from Poland/North America versus Other countries had history of coronary artery disease. MACE IRs were similar in North America and Poland, and numerically higher versus Other countries. IRs for malignancies (excluding NMSC) were numerically higher in North America versus Poland/Other countries with tofacitinib. Serious infections IRs were numerically higher in North America versus Poland across treatments. Venous thromboembolism/all-cause mortality IRs were generally comparable across regions. DAS28-4(CRP)/HAQ-DI improvements were generally lowest in North America.

Conclusions: Differences in safety outcomes were driven by the presence of baseline risk factors; North America and Poland demonstrated a higher proportion of patients with some baseline CV risk factors/comorbidities versus Other countries.

Trial registration: NCT02092467 (ClinicalTrials.gov).

Introduction: The therapeutic arsenal for psoriatic arthritis (PsA) is gradually being expanded, but the use of these targeted treatments must be optimal. Our objective was to guide the choice of targeted therapy to use as first-line treatment in a patient with PsA in whom methotrexate (MTX) has failed.

Methods: We searched for literature data in PubMed with the appropriate keywords for the six points of our argument: (1) the tolerance of MTX; (2) the efficacy of targeted therapies combined with MTX vs monotherapy; (3) immunogenicity of anti-tumor necrosis alpha (TNFα) monoclonal antibodies (mAbs); (4) immunogenicity of anti-interleukin (IL)-17, anti-IL-12/23, and anti-IL-23 mAbs; (5) the therapeutic maintenance of anti-TNFα mAbs when combined or not with MTX; (6) the therapeutic maintenance of anti-IL-17 vs anti-TNFα mAbs as first-line targeted therapy.

Results: The proposed rational strategy is as follows: in case of initiation of an anti-TNFα agent, maintaining treatment with MTX seems preferable, even in the absence of evidence of the superior efficacy of the combination, to avoid immunization and reduced therapeutic maintenance; in case of initiation of anti-IL-17, anti-IL-12/23, anti-IL-23 agents, or Janus kinase (JAK) inhibitors, again in the absence of evidence of the superior efficacy of the combination, discontinuing MTX therapy may be possible, at least in two steps, after verifying the efficacy of the targeted therapy initiated on the joints and skin.

Conclusion: We have data from the literature to guide the choice of targeted therapy to use as first-line treatment in a patient with PsA in whom MTX has failed.

Introduction: Rheumatoid arthritis (RA) guidelines recommend methotrexate (MTX)-anchored therapy with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); however, tolerability issues often lead to non-adherence. Canadian data on MTX tapering and/or withdrawal following b/tsDMARD initiation are minimal. This chart review assessed frequency of MTX tapering or withdrawal following b/tsDMARD initiation and the impact on disease status in Canadian adults with RA.

Methods: Eligible patients had received MTX for ≥ 3 months before b/tsDMARD initiation. The b/tsDMARD was prescribed continuously for ≥ 18 months. Patients taking > 10 mg/day oral prednisone or equivalent were excluded.

Results: Eight hundred eighty-nine patients (mean baseline MTX dose 19.0 mg/week) prescribed b/tsDMARDs (tumor necrosis factor inhibitor 52.1%, Janus kinase inhibitor 18.3%, interleukin-6 inhibitor [IL-6i] 11.9%, other 17.7%) were evaluated at 22 Canadian centers. Within 2 years of b/tsDMARD initiation, MTX was tapered in 123 (13.8%) patients and discontinued in 147 (16.5%), most commonly due to planned tapering (36.6%) and patient decision (27.2%), respectively, and most commonly with IL-6i use (34.9%). The MTX dose was unchanged for 582 (65.5%) patients and increased for 37 (4.2%). Missing data limit interpretations of MTX dose effects on some secondary endpoints and challenge the assertion that a disease activity measure-based treat-to-target approach is routinely used in Canadian rheumatology practice.

Conclusions: Methotrexate tapering or withdrawal occurred in 30.4% of Canadians with RA within 2 years following b/tsDMARD initiation. Baseline disease activity measures were missing from many medical records. However, for patients with baseline assessments, MTX tapering or discontinuation did not worsen disease activity.

Introduction

The 1-year PROspective sarilumab (preFILled syringe/pen) multinational, obsErvational (PROFILE) study evaluated the real-world effectiveness and safety of sarilumab in patients with moderate-to-severe rheumatoid arthritis (RA).

Methods

Safety endpoints included adverse events (AEs) and lab abnormalities. Effectiveness endpoints included the ACR core set. The primary endpoint was the change from baseline in Clinical Disease Activity Index (CDAI). All statistics are descriptive and p values were nominal.

Results

In total, 595 patients were treated, of whom 223 (37.5%) received sarilumab monotherapy and 372 (62.5%) received combination therapy. Upon initiation of sarilumab, an improvement in the mean (SD) CDAI score was observed at week 24 [11.4 (10.3)] and was maintained through week 52 [10.0 (10.5)], resulting in a mean [SD] reduction of −14.9 (12.7) and −14.4 (12.9), respectively. There were consistent improvements in disease activity that were similar for patients on monotherapy vs. combination therapy. An increase in the proportion of patients achieving remission and low disease activity was reported. By week 52, both groups had improved physical function and quality of life. There were no new safety signals. The proportions of any patients reporting a treatment-emergent adverse event (TEAE) or serious treatment-emergent AE (SAE) was 66.2% and 5.9%, respectively, and were similar between both treatment groups. Overall, 15.6% of patients discontinued sarilumab treatment due to TEAEs. The most commonly reported TEAE of interest was neutropenia (14.1%).

Conclusions

In this 1-year, observational real-world study, sarilumab therapy resulted in improved clinical outcomes. The safety profile was consistent with that observed in sarilumab randomized clinical trials.

This study was entered on the German website (Paul Ehrlich Institute) on January 11, 2018, with NIS No.: 423.

This is a summary of the original article ‘Ten-year safety and clinical benefit from open label etanercept treatment in children and young adults with juvenile idiopathic arthritis’. Juvenile idiopathic arthritis (JIA) usually appears before the age of 16. JIA causes pain, swelling, and stiffness in the joints. People with JIA receive treatment for several years until the disease goes into prolonged remission. Therefore, the long-term safety of these treatments is an important topic. Etanercept is a treatment for JIA, which acts on the body’s immune system to reduce arthritis. This summary of research article describes safety and how well etanercept works in children with JIA taking it for up to 10 years.

Introduction

Adhesive capsulitis, also known as “frozen shoulder,” is a debilitating shoulder condition increasingly linked to fibroadhesive bursitis, particularly after COVID-19 and related vaccinations. There is no definitive gold standard for its treatment, the primary therapeutic objectives of which are the reduction of pain and the restoration of shoulder range of motion. The aim of our study was to analyze treatment outcomes based on quantitative measures of shoulder function and symptom relief.

Method

Conducted between January 2022 and April 2023, the research involved 45 patients initially diagnosed with adhesive capsulitis and associated fibroadhesive bursitis. After excluding nine patients for other concomitant pathologies (five for calcific tendinopathy and four for rotator cuff injury), 36 patients were randomized into two groups: one group was treated with glenohumeral hydrodistension, the other with glenohumeral hydrodistension combined with bursal injection. Assessments were conducted at baseline and then 2, 4, and 6 months after treatment, focusing on changes in pain levels, functional scores, and range of motion in all planes. Each group followed a home-based rehabilitation protocol.

Results

Significant improvements were observed in both treatment groups, with the combined hydrodistension and bursal injection group showing notably superior outcomes. Specifically, the range of motion in flexion improved from an initial median of 80° to 155° in the combined treatment group, compared to an increase from 75.5° to 129° in the group treated with hydrodistension alone. This enhancement was statistically significant (p < 0.001).

Regarding pain reduction, the combined treatment group demonstrated a dramatic decrease in visual analogue scale (VAS) scores, from a baseline median of 7 to 1 at the 6-month follow-up. In contrast, the hydrodistension-only group showed a reduction from 7 to 3, with these differences also proving statistically significant (p < 0.001).

Conclusions

Ultrasound-guided hydrodistension of the glenohumeral joint, if combined with bursal injection and specific exercises, effectively reduces pain, decreases disability, and improves range of motion in patients with second-stage adhesive capsulitis. This study highlights the importance of a combined approach in the management of this complex condition, especially after the histological changes that occurred after COVID-19 and related vaccinations.

Trial Registration

ClinicalTrials.gov identifier NCT06062654.