Rheumatology and Therapy最新文献

Introduction: The relative efficacy of bimekizumab and risankizumab in patients with PsA who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR) was assessed at 52 weeks (Wk52) using matching-adjusted indirect comparisons (MAIC).

Methods: Relevant trials were systematically identified. For patients who were bDMARD naïve, individual patient data (IPD) from BE OPTIMAL (NCT03895203; N = 431) were matched with summary data from KEEPsAKE-1 (NCT03675308; N = 483). For patients who were TNFi-IR, IPD from BE COMPLETE (NCT03896581; N = 267) were matched with summary data from the TNFi-IR patient subgroup in KEEPsAKE-2 (NCT03671148; N = 106). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted to match the baseline characteristics of patients in the risankizumab trials. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Recalculated bimekizumab Wk52 outcomes for American College of Rheumatology (ACR) 20/50/70 response criteria and minimal disease activity (MDA) index (non-responder imputation) were compared with risankizumab outcomes via non-placebo-adjusted comparisons.

Results: In patients who were bDMARD naïve, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR50 (odds ratio [95% confidence interval]: 1.52 [1.11, 2.09]) and ACR70 (1.80 [1.29, 2.51]). In patients who were TNFi-IR, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR20 (1.78 [1.08, 2.96]), ACR50 (3.05 [1.74, 5.32]), ACR70 (3.69 [1.82, 7.46]), and MDA (2.43 [1.37, 4.32]).

Conclusions: Using MAIC, bimekizumab demonstrated a greater likelihood of efficacy in most ACR and MDA outcomes than risankizumab in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52.

Trial registration: NCT03895203, NCT03896581, NCT03675308, NCT03671148.

This Summary of Research overviews the results of a study that looked at patient-reported outcomes in the VOLTAIRE-RA trial (NCT02137226), originally published in Rheumatology and Therapy. A biosimilar is a biologic medicine made to be very similar to the original biologic medicine (also known as the reference product). The VOLTAIRE-RA trial compared the efficacy and safety of an adalimumab biosimilar (Cyltezo^®, adalimumab-admb) with the adalimumab reference product, Humira^®, in people with rheumatoid arthritis. As part of the VOLTAIRE-RA study, participants took either adalimumab-adbm or adalimumab reference product for 24 weeks. Patient-reported outcomes were captured after 12 weeks and after 24 weeks of treatment to assess the effects of treatment on each participant's health-related quality of life. People with rheumatoid arthritis who were given adalimumab-adbm or adalimumab reference product experienced similar clinically meaningful improvements in their health-related quality of life after 12 weeks of treatment. A high proportion of people in this trial who were given adalimumab-adbm or adalimumab reference product reported greater improvement versus a reference US population matched by age and sex. This is notable, as it represents a treatment goal that was difficult to achieve in earlier rheumatoid arthritis trials of non-biologic treatments.

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: Patients with chronic refractory gout face a considerable burden of disease due to unexpected flares characterized by severe and debilitating pain, which can lead to chronic pain and joint damage. This study aimed to understand the symptoms and impacts of chronic refractory gout on health-related quality of life (HRQoL).

Methods: A targeted literature review was conducted to identify and review key articles describing the symptoms and impacts of gout, and articles examining the psychometric performance of the Medical Outcomes Survey Short Form-36 (SF-36) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in gout. Qualitative interviews were conducted with 20 participants with chronic refractory gout. The results were used to develop the conceptual model and determine the appropriateness of the SF-36 and HAQ-DI in evaluating HRQoL in this population.

Results: Most frequently reported symptoms included bodily pain (n = 18, 90.0%), joint swelling (n = 18, 90.0%), joint tenderness (n = 18, 90.0%), and joint pain (n = 16, 80.0%). Most frequently reported impacts were difficulties climbing a flight (n = 20, 100.0%) or several flights of stairs (n = 20, 100.0%), climbing five steps (n = 19, 95.0%), completing chores (n = 19, 95.0%), and running errands and shopping (n = 19, 95.0%). All assessed items from SF-36 and HAQ-DI were reported by ≥ 25% (n = 5) of participants and mapped sufficiently to concepts elicited by participants.

Conclusions: Patients with chronic refractory gout report symptoms and impacts that are highly bothersome and burdensome to everyday life. Items included in the HAQ-DI and SF-36 mapped directly to these symptoms and impacts and are relevant to understand the burden of disease of chronic refractory gout.

Introduction

Patients with fibromyalgia (FM) have innumerable complaints due to the central amplification of somatic stimuli. The aim of this paper was to review the ear complaints in patients with FM.

Methods

A review of articles published in PubMed/MEDLINE, Embase, Web of Science, and Scopus from 1966 to June 2023 was performed.

Results

Seventeen papers were included in the review. They showed that patients with FM have a higher hearing loss rate, mostly at high frequencies, and hyperacusis. The prevalence of vestibular symptoms (tinnitus, dizziness) and hyperacusis was higher than in the general population, reaching 87.0% of the sample. Subjective findings did not always correspond to objective results. In some studies, the degree of FM severity was associated with ear symptoms; in others, it was not.

Conclusions

Ear complaints in patients with FM are linked to subjacent disease and may be related to stimuli central amplification.

Introduction: To assess differences in the diagnosis journey and access to care in a large sample of patients with axial spondyloarthritis (axSpA) from around the world, included in the International Map of Axial Spondyloarthritis (IMAS).

Methods: IMAS was a cross-sectional online survey (2017-2022) of 5557 unselected patients with axSpA from 27 countries. Across five worldwide geographic regions, the patient journey until diagnosis and healthcare utilization in the last 12 months prior to survey were evaluated. Univariable and multivariable linear regression was used to analyze factors associated with higher healthcare utilization.

Results: Of 5557 participants in IMAS, the diagnosis took an average of 7.4 years, requiring more than two visits to HCPs (77.7% general practitioner and 51.3% rheumatologist), and more than two diagnostic tests [67.5% performed human leukocyte antigen B27 (HLA-B27), 64.2% x-ray, and 59.1% magnetic resonance imaging (MRI) scans]. North America and Europe were the regions with the highest number of healthcare professional (HCP) visits for diagnosis, while the lowest number of visits was in the Asian region. In the previous 12 months, 94.9% (n = 5272) used at least one healthcare resource, with an average of 29 uses per year. The regions with the highest healthcare utilization were Latin America, Europe, and North America. In the multiple linear regression, factors associated with higher number of healthcare utilization were younger age (b =  - 0.311), female gender (b = 7.736), higher disease activity (b = 1.461), poorer mental health (b = 0.624), greater functional limitation (b = 0.300), greater spinal stiffness (b = 1.527), and longer diagnostic delay (b = 0.104).

Conclusion: The diagnosis of axSpA usually takes more than two visits to HCPs and at least 7 years. After diagnosis, axSpA is associated with frequent healthcare resource use. Younger age, female gender, higher disease activity, poorer mental health, greater functional limitation, greater spinal stiffness, and longer diagnostic delay are associated with higher healthcare utilization. Europe and North America use more HCP visits and diagnostic tests before and after diagnosis than the other regions.

Introduction: A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab.

Methods: Individual patient data from BE MOBILE 2 (bimekizumab 160 mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150 mg), MEASURE 3 (secukinumab 300 mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI).

Results: At week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150 mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300 mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80 mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure.

Conclusions: Patients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150 mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80 mg were mostly non-significant, depending on the populations considered.

Introduction: Glucocorticoids (GCs) play a crucial role in the treatment of many rheumatic diseases regarding their anti-inflammatory and immunosuppressive effects. Inappropriate use of GCs can exacerbate GC-related problems besides complex treatment regimens and miscellaneous well-established adverse events. Although several guidelines exist for managing these problems, there is lack of real-life studies evaluating the problems at the patient level. This study aims to identify GC-related problems among patients with rheumatic diseases and address how they have been solved.

Methods: This prospective follow-up study was conducted between January 2021 and June 2022 at a university rheumatology outpatient clinic and included patients using GCs. A clinical pharmacist assessed patients for possible GC-related problems at baseline, 3 months, and 6 months. Identified problems, their causes, interventions to address these problems, and their outcomes were categorized using the Pharmaceutical Care Network Europe (PCNE v9.1) classification system. The resolution of the problems was evaluated at the patient's next follow-up visit.

Results: A total of 156 patients were included, and 236 GC-related problems were identified in 66% of the patients. Adverse drug events (possible) accounted for the highest proportion of GC-related problems (94.1%), and the most common causes were lack of laboratory monitoring of GC-related adverse events (41.5%) and lack of drug treatment despite existing indications (39.8%). The median cumulative prednisolone dose was higher in patients with GC-related problems (3115 vs. 5455 mg, p = 0.007). The clinical pharmacist suggested 381 interventions: 47.7% (n = 182) at the 'prescriber level', 31.8% (n = 121) at the 'patient level', and 20.5% (n = 78) at the 'drug level'. Of those interventions, 98% were accepted, and 80.1% of the problems were solved.

Conclusions: This study showed that the prevalence of GC-related problems is high in patients with rheumatic diseases. Integrating clinical pharmacists into the multidisciplinary rheumatology team provides an advantage in effectively identifying and managing GC-related problems at an early stage.

Introduction: Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody treatments. QX002N injection, as a new monoclonal antibody targeting IL-17A, has shown potential in treating AS, offering a new treatment option for patients who do not respond well to existing therapies.

Methods: A randomized, open, parallel, single-center, phase I study was conducted to assess the pharmacokinetics, safety, and immunogenicity of single doses of QX002N injection administered intravenously (IV) or subcutaneously (SC) to healthy Chinese volunteers. Blood samples were collected at specified time intervals, and then serum concentrations of QX002N were analyzed by enzyme-linked immunosorbent assay.

Results: Pharmacokinetic analysis of the drug concentration-time data showed that the mean maximum observed serum QX002N concentration (C_max) was 110 and 33.9 µg/ml, respectively. The average area under the drug concentration-time curves from 0 to the time of the last quantifiable concentration (AUC_last) were 52,656 and 36,269 µg·h/ml, respectively and the average area under the drug concentration-time curves from 0 to infinity (AUC_inf) were 54,867 and 38,194 µg·h/ml, respectively. The absolute bioavailability of QX002N after SC injection was 69.6%.

Conclusions: Immunogenicity was assessed and all the subjects in this study were Anti-drug antibody (ADA)-negative, which means no subjects appeared to develop immunogenicity to QX002N. All the results testify to the safety of QX002N injection, which is satisfactory after IV or SC dosing in healthy subjects.

Trial registration: www.chinadrugtirals.org.cn , CTR20220430.

Introduction: With an increasing number of biologic/targeted synthetic disease-modifying antirheumatic drug options available for the treatment of active ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis, it is of clinical interest to determine the comparative efficacy of these advanced therapies among populations with differing prior advanced therapy exposure. This study aimed to assess the comparative efficacy of approved advanced therapies for AS in tumor necrosis factor inhibitor (TNFi)-naïve and, separately, in TNFi inadequate responder/intolerant (-IR) populations.

Methods: A systematic literature review was conducted to identify randomized clinical trials for TNFis, interleukin-17A inhibitors, and Janus kinase inhibitors used as advanced therapies for active AS. Clinical efficacy was considered by the Ankylosing Spondylitis Disease Activity Score low disease activity (ASDAS LDA) criteria, defined as ASDAS score less than 2.1, among approved therapies. Comparative efficacy in the TNFi-naïve population was assessed utilizing network meta-analysis, while comparative efficacy in the TNFi-IR population was assessed utilizing matching-adjusted indirect comparison. Odds ratios were calculated, from which absolute rates and numbers needed to treat were calculated. Safety in the form of trial-reported and placebo-adjusted rates of discontinuation due to adverse events (AEs) was reviewed.

Results: Among the TNFi-naïve population, the estimated ASDAS LDA rate between week 12 and 16 was highest for patients treated with upadacitinib (52.8%) and lowest for patients treated with placebo (11.6%). Among the TNFi-IR population, the estimated ASDAS LDA rate was 41.3% for patients treated with upadacitinib and 17.5% for patients treated with ixekizumab. The trial-reported and placebo-adjusted rates of discontinuation due to AEs were generally low across included advanced therapies.

Conclusions: Relative to other assessed therapies, upadacitinib demonstrated greater clinical efficacy per ASDAS LDA in the treatment of active AS in both TNFi-naïve and TNFi-IR populations. Head-to-head and real-world data comparisons are warranted to both validate these findings and aid medical decision makers.