Rheumatology and Therapy最新文献

Introduction: An intriguing aspect that emerged in recent years is the transition phase from psoriasis (PsO) to psoriatic arthritis (PsA). The PRESTO instrument allows estimating a patient's risk of developing PsA based on a few clinical items. The aim of this study was to apply and evaluate the performance of the PRESTO tool in a cohort of patients with PsO.

Methods: Consecutive patients with PsO were enrolled. Dermatological and rheumatological assessment was carried out in order to evaluate clinical features of PsO, to exclude the diagnosis of PsA, and to administer the PRESTO tool.

Results: Between January 1, 2024 and April 1, 2024, 100 patients were assessed. Eight-four patients found the questionnaire to be very useful and easy. The estimated risk (median/IQR) of 1-year progression to PsA found in our group was 2.45% at 1 year (1.1-4).

Conclusions: The PRESTO instrument was feasible and well accepted by patients. The 1-year risk assessed by PRESTO tools is consistent with other reports in the literature.

Introduction: We assessed tofacitinib efficacy and safety in ankylosing spondylitis (AS) by body mass index (BMI) category.

Methods: Data were pooled from phase 2/3 trials; analyses included patients with active AS randomized (1:1) to tofacitinib 5 mg twice daily or placebo, who were stratified by baseline BMI into < 25, ≥ 25 to < 30, and ≥ 30 kg/m² categories. Efficacy was assessed at week 12 and safety to week 16.

Results: Of 370 patients, 153, 131, and 86 had a baseline BMI  of < 25, ≥ 25 to < 30, and ≥ 30 kg/m², respectively. At baseline, patients with BMI < 25 kg/m² were younger and more likely to be current smokers/Asian, and patients with BMI ≥ 30 kg/m² had higher mean waist circumference/swollen joint count (SJC) and were more likely to have enthesitis, high-sensitivity C-reactive protein (hsCRP) > 5 mg/L, an inadequate response to tumor necrosis factor inhibitors (TNFi), and prior biologic disease-modifying anti-rheumatic drug (bDMARD) use versus other categories. Across categories, tofacitinib responses/improvements were greater than with placebo, except for ≥ 40% Assessment of SpondyloArthritis international Society improvement (ASAS40), ASAS partial remission, 50% improvement from baseline in the Bath Ankylosing Spondylitis Disease Activity Index score (BASDAI50), and Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) inactive disease rates, which were similar for tofacitinib and placebo in the BMI ≥ 30 kg/m² category. Treatment effects were similar across categories, except for BASDAI50, which was smaller in the BMI ≥ 30 category versus  the < 25 kg/m² category. More adverse events (AEs) and serious adverse events (SAEs) with tofacitinib were reported in the BMI < 25 kg/m² category, which had a higher proportion of current smokers versus other categories.

Conclusions: Regardless of baseline BMI category, efficacy was greater with tofacitinib versus placebo in patients with AS, and no treatment effect differences between categories were observed, with exceptions for BMI ≥ 30 kg/m² (more active/treatment-refractory disease and a smaller sample size). Overall, tofacitinib safety was generally comparable across categories; however, AE/SAE rates with tofacitinib were higher in the BMI < 25 kg/m² category (which had more current smokers). This post hoc analysis demonstrates that tofacitinib can be considered as a treatment option for AS, regardless of baseline BMI category; however, interpretation was limited by small sample sizes and differences in sample sizes and baseline characteristics across categories.

Trial registration: ClinicalTrials.gov identifiers, NCT01786668 and NCT03502616.

Introduction: Fatigue is a key symptom in patients with ankylosing spondylitis (AS). The objective of this analysis was to estimate the median time to initial and stable improvement events in fatigue in patients with AS receiving tofacitinib.

Methods: This post hoc analysis used data from a phase 3 trial (NCT03502616) in patients with active AS receiving tofacitinib 5 mg twice daily or placebo. Time to improvement in fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score, experience domain score, and impact domain score. The rapidity of improvement was assessed by time-to-event analyses (nonparametric Kaplan-Meier models); initial improvement events (i.e., time to first week of FACIT-F improvement) and stable improvement events (i.e., time to first week of FACIT-F improvement, sustained to 16 weeks) were examined.

Results: Overall, 269 patients were assessed (mean disease duration: 14.2 [standard deviation (SD): 9.8] years; mean baseline FACIT-F total score: 27.2 [SD: 9.3]). Median times to initial and stable improvement events in FACIT-F total and domain scores were significantly shorter and occurred in more patients receiving tofacitinib than placebo. Median time to initial and stable improvement events of 6 points in FACIT-F total score were 8 and 12 weeks with tofacitinib, respectively (placebo: not reached); 70.0% versus 48.5% of patients receiving tofacitinib versus placebo, respectively, experienced initial improvements of 6 points in FACIT-F total score within 16 weeks.

Conclusions: Improvements in fatigue occurred more rapidly with tofacitinib than with placebo. These results may be useful for healthcare providers when discussing tofacitinib treatment expectations with patients.

Trial registration: ClinicalTrials.gov: NCT03502616 (June 7, 2018).

Introduction: Rheumatoid factor (RF) plays an important role in rheumatoid arthritis (RA) pathophysiology, yet the differential effects of varying RF titers remain understudied. We evaluated associations between different RF titers and clinical outcomes in long-standing RA.

Methods: This multicenter, cross-sectional study included adults meeting ACR/EULAR (2010) criteria for RA. Circulating RF titers and clinical-epidemiological characteristics were evaluated. Bivariate (Student's t and chi-squared tests) tests and multiple logistic and linear regression analyses were conducted.

Results: We included 1097 participants; 78.7% had positive RF, with high titers (≥ 3 × the upper limit of normality) in 56.2%. Negative vs. low-positive RF groups performed similarly concerning all clinical outcomes, being subsequently aggregated as "non-high" RF group. High RF titers (compared to "non-high") were associated with tobacco use (odds ratio, OR [95% confidence interval, CI]: 2.04 [1.35, 3.08]; p < 0.001), multiraciality (OR [95% CI] 1.31 [1.03, 1.67]; p = 0.028, compared to White race), and higher body mass index (mean difference [95% CI] 0.69 [0.05, 1.33] kg/m²; p = 0.033). In multivariate analyses, high-titer RF was independently associated with higher disease activity (Clinical Disease Activity Index, CDAI: β = 2.44 [0.89, 3.99], p = 0.002), worse functional capacity (Health Assessment Questionnaire Disability Index, HAQ-DI: β = 0.112 [0.018, 0.205], p = 0.020); extra-articular manifestations (OR 1.48 [1.09, 2.00], p = 0.011); increased corticosteroid (OR 1.53 [1.19, 1.96], p = 0.001) and biological disease-modifying antirheumatic drugs (bDMARD) use (OR 1.41 [1.08, 1.84], p = 0.011).

Conclusions: High RF titers in long-standing RA were associated with worse disease activity, lower physical functionality, increased extra-articular manifestations, and higher usage of corticosteroids and bDMARDs. Comparing high vs. non-high RF titers (rather than positive vs. negative RF) seems more useful for evaluating the clinical effects of RF in RA. This approach should be considered in future studies of RF.

Introduction: Interim analysis of the long-term safety and effectiveness of canakinumab, at a patient level, in the mevalonate kinase deficiency/hyperimmunoglobulin-D syndrome (MKD/HIDS) cohort of the RELIANCE registry.

Methods: From June 2018, the RELIANCE registry enrolled paediatric (aged ≥ 2 years) and adult patients (aged ≥ 18 years) with MKD/HIDS who were receiving canakinumab as part of their routine medical care. Safety, physician- and patient-reported measures of disease activity and dosing patterns were evaluated at baseline and every 6 months until end-of-study visit.

Results: At the analysis cut-off date of December 2022, eight patients with MKD/HIDS were enrolled. Five (62.5%) were children (< 18 years) and five (62.5%) were female. The median patient age was 8.0 (range 2.0-39.0) years, and all patients were pre-treated with canakinumab prior to enrolment (median duration of canakinumab treatment: 3.8 years). Canakinumab was well tolerated, with seven (87.5%) patients reporting 48 adverse events (incidence rate/100 patient years: 218.1). No serious adverse drug reactions were reported. Patients continued to receive vaccinations during long-term treatment with canakinumab. Disease activity, evaluated by physician-reported (physician's global assessment, disease remission, C-reactive protein, serum amyloid A, erythrocyte sedimentation rate) and patient-reported (autoinflammatory disease activity index diary, disease activity, fatigue, impact on social life) measures, was generally well controlled throughout the study. Over 50.0% of patients maintained disease remission from baseline to month 24, and medians of all inflammatory markers remained within normal limits throughout the study. Most patients received higher than the recommended starting dose of canakinumab throughout the study.

Conclusion: Data from this interim analysis of a unique registry of patients with a rare disease support the long-term safety and effectiveness of the IL-1-blocking agent canakinumab for the treatment of MKD/HIDS.

Introduction: This study sought to describe treatment patterns, persistence, and effectiveness of upadacitinib (UPA) alone and compared to other Janus kinase inhibitors (JAKis) or tumor necrosis factor inhibitors (TNFis) in patients with rheumatoid arthritis (RA).

Methods: This retrospective, non-interventional study used the OPAL dataset, derived from electronic medical records. Patients initiated UPA (N = 2624), other JAKis (baricitinib and tofacitinib [N = 925]), or TNFis (adalimumab, etanercept, certolizumab, golimumab, infliximab [N = 3540]) between May 2020 and March 2023. Median persistence (Kaplan-Meier) and effectiveness (Disease Activity Score 28-joint C-reactive protein, three variables [DAS28CRP{3}]) were evaluated for UPA-treated patients and in three propensity score-matched cohorts: UPA monotherapy versus combination therapy, UPA versus other JAKis, and UPA versus TNFis.

Results: In patients prescribed UPA, 41.3% were ≥ 65 years old, 33.8% were prescribed as first-line advanced therapy, and 27.2% were prescribed monotherapy. Persistence on UPA was 26.6 months (95% confidence intervals: 24.4, 29.9) and longest in earlier lines of therapy. The DAS28CRP(3) remission rate was 73% at 3 months, with improvements observed across lines of therapy. UPA monotherapy and combination therapy had similar persistence (27.8 [23.5, 33.4] versus 30.4 months [22.1, 35.3], p = 0.84) and effectiveness. UPA showed longer persistence than other JAKis (28.8 [25.6, 32.4] versus 17.2 months [14.9, 19.8], p < 0.001) and TNFis (26.6 [24.9, 30.8] versus 13.3 months [11.5, 14.5], p < 0.001). DAS28CRP(3) remission rates were greater at 3 months for UPA than other JAKis (75.0% versus 61.5%) and TNFis (72.7% versus 59.5%). In unmatched subgroups, compared to cycling between TNFis, switching to UPA from other JAKis or TNFis resulted in longer persistence (JAKi-to-UPA: 25.3 [16.1, not reached]; TNFi-to-UPA: 27.8 [23.2, 35.4]; TNFi-to-TNFi: 9.6 [8.4, 10.7]) and greater DAS28CRP(3) remission rates over 9 months.

Conclusions: Overall, the breadth and depth of data from this large real-world dataset continue to support a favorable clinical profile of UPA for the treatment of RA and may inform treatment choices in everyday clinical practice.

Objective: Gout is a progressive form of arthritis that causes significant pain and disability. Patients with treatment-refractory (or uncontrolled) gout experience a higher prevalence and severity of comorbidities than those whose gout is controlled. Pegloticase is a recombinant PEGylated uricase indicated for the treatment of gout in patients refractory to conventional therapy. We evaluated the treatment journey of patients with chronic uncontrolled gout before initiation of pegloticase therapy.

Methods: Using IQVIA's PharMetrics^® Plus database, we conducted a retrospective observational analysis of adults with ≥ 1 pegloticase claim between April 1, 2011, and August 31, 2020. Demographics were assessed at baseline. Clinical outcomes, health care resource utilization (HCRU), and associated costs were compared over two 12-month periods (months 13-24 and 1-12) prior to the first pegloticase claim (index date).

Results: The study included 408 patients. Prevalence of all gout-associated conditions increased between months 1-12 and 13-24 (P < 0.05 for all). The percentage of patients with tophi increased from 15.4% to 61.5%, the percentage with ≥ 1 flare increased from 49% to 84%, and mean number of flares per patient increased from 1.0 to 2.1 (P < 0.0001 for all). The frequency of all categories of HCRU except emergency department visits also increased (P < 0.0001 for all), as did gout-related healthcare utilization (P£0.005).

Conclusions: Patients with uncontrolled gout experienced an increase in the clinical burden of disease and HCRU in the 2 years before the initiation of pegloticase. Earlier patient identification and initiation of potentially effective therapy may help alleviate these burdens.

Introduction: Inflammatory bowel disease (IBD) related arthritis is the most prevalent extraintestinal manifestation (EIM) of IBD, ranging between 10 and 39%. Magnetic resonance enterography (MRE) is used to assess small bowel disease involvement in Crohn's disease (CD) and can detect signs of sacroiliitis in up to 23.5% of patients. The predicting role of sacroiliitis detected on MRE is still unknown. The aim of this study is to evaluate the predictive role of sacroiliitis at MRE and other clinical features for IBD-related arthritis development in a cohort of adult patients with CD.

Methods: Between December 2012 and May 2020, consecutive patients with CD who performed MRE were enrolled in the study. Patients with a previous diagnosis of IBD-related arthritis were excluded. A baseline demographics and clinical characteristics of the patients were retrospectively collected. The identification of new-onset IBD-related arthritis events during the follow-up was based on rheumatological clinical diagnosis and fulfillment of the ASAS classification criteria.

Results: Ninety-five patients, mean age 43.9 years (standard deviation [SD] ± 16.6), 52.6% female were enrolled in the study with a median follow-up of 83 months (Q25:75 25:143). Six out 95 (6.3%) developed IBD-related arthritis with a mean time of 11 months (SD ± 16.8). Sacroiliitis detected on MRE was not associated with an increased risk of IBD-related arthritis (odds ratio [OR] = 2.12 [95% confidence interval (CI) 0.36, 12.53, p = 0.408]). In contrast, the presence of arthralgia and EIMs were found to be a predictor for IBD-related arthritis development (OR = 84.0 [95% CI 8.18, 862.39, p < 0.0001] and OR = 7.37 [95% CI 1.25, 43.32, p = 0.027], respectively).

Conclusions: This study highlights that sacroiliitis, as assessed by MRE, was not associated with the development of IBD-related arthritis, whereas extraintestinal manifestations and arthralgia were significantly associated with later IBD-related arthritis development in patients with CD.

Introduction: We aim to assess the association of patient-reported pain and remission or low disease activity (LDA) at 3 months (M) in patients receiving baricitinib or other treatments in RA-BE-REAL.

Methods: RA-BE-REAL reports on patients with rheumatoid arthritis (RA) who were prescribed, for the first time, baricitinib (cohort A) or a tumour necrosis factor inhibitor (TNFi) (cohort B-TNFi) or any other mode of action (OMA) (cohort B-OMA). Pain was measured using the visual analogue scale (VAS) (0-100 mm) and clinically meaningful pain improvement thresholds of ≥ 30%, ≥ 50% and ≥ 70% from baseline to 3, 6, 12 and 24 M.

Results: At 3 M, the mean change from baseline (CFB) pain VAS of patients in remission/LDA was - 32.6 mm (cohort A), - 27.3 mm (cohort B-TNFi) and - 28.0 mm (cohort B-OMA). Almost half the patients who were in remission/LDA receiving baricitinib achieved ≥ 70% pain relief. At 3 M, the proportion of patients in remission/LDA with pain VAS ≤ 20 mm was 62.1% (cohort A), 55.0% (cohort B-TNFi) and 55.6% (cohort B-OMA), while for those not in remission/LDA, it was 8.5% and 8.7% (cohort A and B-TNFi, respectively) and 5.3% (B-OMA). More patients on baricitinib achieved pain improvement in all analyzed thresholds than patients in cohort B-TNFi and B-OMA at 3 M. At 24 M, - 26.2 mm (cohort A), - 20.8 mm (cohort B-TNFi) and - 16.0 mm (cohort B-OMA) mean CFBs in pain measurement were observed. For baricitinib and the other treatments, residual pain decreased with achievement of remission/LDA and was sustained up to 24 M.

Conclusions: Patients in remission/LDA receiving baricitinib are more likely to achieve pain control than patients receiving TNFi/OMA.

Introduction: While modern treatments can prevent progressive bone destruction in patients with rheumatoid arthritis (RA) achieving clinical remission, it is unclear whether residual clinical activity may cause or be associated with progressive joint damage. This post hoc analysis evaluated the association between clinical disease activity and structural progression in patients with RA treated with filgotinib (FIL) in FINCH 1 (NCT02889796).

Methods: Patients with RA and inadequate response to methotrexate (MTX) use were randomized 3:3:2:3 to FIL 200 mg (FIL200) or FIL 100 mg (FIL100) once daily, adalimumab 40 mg biweekly, or placebo, all with background MTX. We evaluated the change from baseline (CFB) in modified total Sharp score (mTSS), erosion score, and joint space narrowing score among patients achieving Clinical Disease Activity Index (CDAI) remission (CDAI ≤ 2.8), low disease activity (LDA; 2.8 < CDAI ≤ 10), medium disease activity (MDA; 10 < CDAI ≤ 22), and high disease activity (HDA; CDAI > 22) at 24 weeks.

Results: At week 24, the least squares (LS) mean CFB in mTSS was similarly low across treatments among patients who achieved CDAI remission (range 0.00-0.11) or LDA (n = 285 and 575, respectively). In patients with MDA and HDA (n = 471 and 157, respectively), smaller LS mean CFB in mTSS was seen in the FIL200 group vs. the placebo group (P < 0.05 for both).

Conclusions: RA clinical remission and LDA achievement were associated with suppressed progression of joint destruction over 24 weeks in all treatment groups. Only FIL200 significantly inhibited joint damage compared with placebo in patients with MDA or HDA, indicating an uncoupling of clinical disease activity and structural progression in patients receiving FIL200.

Trial registration: NCT02889796.