Rheumatology and Therapy最新文献

Introduction: This work aims to describe the risk of major adverse cardiovascular events (MACE), malignancy, and mortality in real-world patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) treated with subcutaneous (SC) golimumab.

Methods: This post hoc analysis included patients treated with SC golimumab from the BioTRAC registry. Incidence rates (IR) per 100 patient-years (PYs) and time to onset of adverse events of special interest (AEoSI), including MACE, malignancies, mortality, serious AEs (SAEs), and serious infections (SIs), were assessed in subgroups based on age, sex, prior tumor necrosis factor inhibitor experience, smoking status, and baseline methotrexate and oral steroid use. All analyses were stratified by indication.

Results: Of 1231 patients included, 529 had RA, 281 had PsA, and 421 had axSpA. At baseline, mean patient age was 57.7, 52.8, and 45.7 years in the RA, PsA, and axSpA groups, respectively. Most patients with RA (76.2%) and PsA (53.7%); 40.9% of patients with axSpA were female. The IR (95% confidence interval) for MACE was 1.1 (0.6, 2.0) events/100 PYs in the RA group with no events in the PsA and axSpA groups. Malignancy IRs were 1.4 (0.8, 2.3), 0.4 (0.0, 1.3), and 1.0 (0.4, 2.1)/100 PYs. SAE incidence ranged from 7.6 (5.5, 10.3)/100 PYs in the PsA group to 11.4 (9.4, 13.6) in the RA group, and that of SIs from 1.3 (0.5, 2.7)/100 PYs in patients with PsA to 2.3 (1.4, 3.4) in patients with RA. IRs for mortality were 0.7 (0.3, 1.4; n = 7), 0.2 (0.0, 1.0; n = 1), and 0.3 (0.0, 1.1; n = 2)/100 PYs in RA, PsA, and axSpA, respectively. Older patients with RA had a significantly shorter time to MACE (p = 0.007).

Conclusions: Patients with RA, PsA, and axSpA treated with SC golimumab in the real world had a low incidence of MACE, malignancy, and all-cause mortality, further confirming the safety of golimumab for the treatment of rheumatic diseases.

Trial registration number and date: ClinicalTrials.gov identifier, NCT00741793, August 22, 2008.

Introduction: Sjögren's disease (SjD) is often characterized by the presence of anti-SSA/Ro and anti-SSB/La autoantibodies. The Clinical European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ClinESSDAI) and Patient-Reported Index (ESSPRI) assess disease activity and patient-reported symptomatology; however, their association with patient-reported outcome measures (PROMs) remains unclear. We aimed to describe systemic disease activity in seropositive and seronegative SjD patients and evaluate the association between proxy ClinESSDAI and ESSPRI scores with PROMs.

Methods: Data were drawn from the Adelphi Real World SjD Disease Specific Programme™, a cross-sectional survey conducted in France, Germany, Italy, Spain and the United States between June and October 2018. Physicians reported patient demographics and clinical characteristics. Patients completed the EQ-5D-3L and Visual Analogue Scale (EQ-VAS), and the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F). Proxy ClinESSDAI and ESSPRI scores were calculated using physician-reported organ activity and averaged patient ratings of dryness, pain, and fatigue, respectively. Associations between ClinESSDAI, ESSPRI, physician-reported disease severity, and PROMs were determined using linear and logistic regression modeling. Statistical significance was p < 0.05 for all tests.

Results: Overall, 319 rheumatologists provided data on 1879 patients with SjD. Mean (standard deviation) patient age was 53.2 (12.2) years, 89% were female, and 89% were White. Of patients who received serum antibody testing for both anti-SSA/Ro and anti-SSB/La antibodies (n = 1344), 69% were double seropositive and 6% were double seronegative. The most common symptoms experienced by double seropositive and double seronegative SjD patients, respectively, included dry eyes (94% and 74%), and physical fatigue (82% and 60%). ClinESSDAI and ESSPRI were significantly associated with EQ-5D-3L, EQ-VAS, and FACIT-F (all p < 0.001).

Conclusions: Systemic disease activity and patient-reported symptomatology were significantly associated with health-related quality of life measures, highlighting the need for disease management that considers both clinical outcomes and the patient experience.

Introduction: This is an interim analysis of the long-term effectiveness and safety of canakinumab in the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) cohort of the RELIANCE non-interventional study.

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

Results: A total of 21 patients with TRAPS were enrolled by the analysis cut-off date of December 2022, of which 61.9% (13/21) were paediatric patients (< 18 years) and 66.7% (14/21) were female. All patients were pre-treated with canakinumab prior to enrolment (median duration of canakinumab treatment prior to study inclusion: 1.2 years). Disease activity, evaluated by physician-reported (physician's global assessment, disease remission, C-reactive protein, serum amyloid A) and patient-reported (disease activity, fatigue, impact on social life, autoinflammatory disease activity index diary) measures, was generally well controlled throughout the study. At baseline, the majority of patients (71.4%) were receiving the recommended starting dose (SD) of canakinumab, with a more even distribution between the < SD, SD, and > SD dosing schedules observed from month 6. No serious adverse drug reactions were reported. Patients continued to receive vaccinations during long-term treatment with canakinumab. In total, 85.7% (18/21) of patients met the Eurofever/PRINTO classification criteria for TRAPS, 42.9% (9/21) with the presence of a confirmative TNFRSF1A genotype and 42.9% (9/21) without. In total, 14.3% (3/21) of patients did not meet the classification criteria.

Conclusions: Data from this interim analysis support the long-term effectiveness and safety of canakinumab for the treatment of TRAPS.

Introduction: This study aimed to evaluate a subsequent treatment response among patients with rheumatoid arthritis (RA) who initiated and remained on a first-line tumor necrosis factor inhibitor (TNFi) after achieving or not achieving an initial response.

Methods: This real-world, retrospective cohort study included patients with RA in moderate/high disease activity (MDA/HDA), defined by Clinical Disease Activity Index (CDAI) score > 10, who initiated a first-line TNFi and remained on therapy for ≥ 12 months. Data were analyzed according to the time of initial evaluation: 3 months (N = 1215) or 6 months (N = 1318).

Primary outcome: proportion of patients achieving low disease activity (LDA)/remission in CDAI (≤ 10) at the initial evaluation; secondary outcome: proportion of patients achieving minimal clinically important difference (MCID) in CDAI. Patients were categorized as responders or nonresponders according to outcome achievement, then analyzed for subsequent response at 12 months and maintenance of initial response through 12 months.

Results: After 3 months, 65.9% of patients were in MDA/HDA. Among these nonresponders, 73.5% remained in MDA/HDA at 12 months and 64.2% failed to improve through 12 months. Of patients in LDA/remission at 3 months, 27.0% lost their response at 12 months. Among the 59.2% of nonresponders at 6 months, 80.1% were in MDA/HDA at 12 months and 74.5% never improved through 12 months. For patients in LDA/remission at 6 months (40.8%), 23.4% subsequently lost their response at 12 months. Similar trends were observed for achievement of MCID in CDAI.

Conclusions: In patients with RA treated with a first-line TNFi, most patients who did not achieve a treatment target at an initial evaluation also failed to achieve the treatment target at 12 months. Therefore, evaluating treatment as early as 3 months after initiation may help indicate future clinical improvements and could serve as a reasonable timepoint to consider changing therapy for patients with an inadequate response.

Introduction: There is limited prior literature comparing long-term treatment persistence between guselkumab and subcutaneous (SC) tumor necrosis factor inhibitors (TNFi) in biologic-naïve and biologic-experienced patients with active psoriatic arthritis (PsA). This study compared on-label persistence through 24 months between patients with active PsA newly initiating guselkumab or SC TNFi.

Methods: IQVIA PharMetrics^® Plus database was used to identify adults with active PsA initiating guselkumab or an SC TNFi (adalimumab or biosimilar, certolizumab pegol, etanercept or biosimilar, SC golimumab) between 07/14/2020 and 12/31/2022 (index date: first treatment claim for one of these medications). Patients were further stratified as biologic-naïve (no pre-index biologic disease-modifying antirheumatic drug [bDMARD] claim) or biologic-experienced (≥ 1 pre-index bDMARD claim). The guselkumab and SC TNFi cohorts were balanced using overlap propensity score weighting. Treatment persistence with on-label therapy (absence of dose modification or therapy exposure gap of twice the duration between consecutive administrations, i.e., 112 days for guselkumab or 56 days for SC TNFi) was estimated using weighted Kaplan-Meier analysis through 24 months. On-label persistence rates were compared between cohorts using weighted Cox proportional hazards models.

Results: In the guselkumab cohort (N = 804), 361 (44.9%) were biologic-naïve and 443 (55.1%) were biologic-experienced; in the SC TNFi cohort (N = 2490), 2171 (87.2%) were biologic-naïve and 319 (12.8%) were biologic-experienced. At 24 months post index, on-label persistence rates were 45.5% (guselkumab) versus 28.5% (SC TNFi; P < 0.001). Patients initiating guselkumab were 2.24 times more likely to be persistent with on-label therapy through 24 months than patients initiating an SC TNFi (hazard ratio [95% confidence interval] 2.24 [1.90, 2.64]; P < 0.001). Results were consistent among biologic-naïve (2.36 [1.88, 2.98]; P < 0.001) and biologic-experienced patients (1.86 [1.46, 2.37]; P < 0.001).

Conclusion: Patients with active PsA initiating guselkumab were significantly (approximately two times) more likely to remain persistent with on-label therapy through 24 months versus SC TNFi, overall and among biologic-naïve and biologic-experienced subgroups.

Introduction: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A and was approved to treat patients with active psoriatic arthritis (PsA) in the European Union in 2023. This study compares the cost per responder (CPR) of bimekizumab against IL-17A (secukinumab), IL-12/23 (ustekinumab) and IL-23 (guselkumab and risankizumab) targeted therapies to treat patients with PsA in Spain.

Methods: The CPR was calculated by dividing the average annual drug cost per patient by the response rates for minimal disease activity (MDA) and American College of Rheumatology (ACR) 50 and ACR70 at week 52 in patients who were biological disease-modifying antirheumatic drug (bDMARD) naïve or who had experienced inadequate response or intolerance to tumour necrosis factor inhibitors (TNFi-IR). Response rates from four published matching-adjusted indirect comparisons (MAIC) were used. Spanish list prices and Royal Decree Law 8/2010 discounts were considered.

Results: In bDMARD-naïve patients, bimekizumab had a lower CPR for MDA and ACR70 versus all comparators except for secukinumab 150 mg, where the CPR for bimekizumab was higher for all three efficacy measures. The incremental CPR ranged between 17.2% (95% confidence interval [CI] - 26.1%, 50.6%) for ACR70 and 92.7% (95% CI 60.0%, 119.4%) for ACR50. The incremental CPR for ACR50 for bimekizumab compared to secukinumab 300 mg was also slightly higher (2.3% [95% CI - 12.5%, 14.3%]). In patients with TNFi-IR, bimekizumab was more cost-efficient than all comparators for the three response rate measures at week 52.

Conclusion: CPR analyses based on MAIC response rates at week 52 suggest that bimekizumab is more cost-efficient than IL-12/23 and IL-23 therapies, including ustekinumab, guselkumab and risankizumab, for treating PsA in Spain across both bDMARD-naïve patients and patients with TNFi-IR for all outcomes (MDA, ACR50/70). Compared to IL-17A (secukinumab), bimekizumab is consistently cost-efficient in patients with TNFi-IR for all outcomes and is cost-efficient in bDMARD-naïve patients versus those taking 300 mg regarding MDA and ACR70.

Introduction: Osteoarthritis (OA) is associated with joint pain and disability, with increasing prevalence and economic burden. This study explored non-steroidal anti-inflammatory drugs (NSAID) treatment patterns, gastrointestinal (GI) complications and burden of disease in patients with OA based on Nordic registry data, with emphasis on individuals aged 60 or younger.

Methods: This non-interventional observational study analysed registry data from Norway, Finland, and Sweden. Adults with primary OA diagnosis in specialty care were matched 1:1 by age and sex with individuals of the general population. The primary outcome was NSAID treatment patterns, assessed by dispensations and daily defined doses (DDD) 1 year before and after diagnosis. Secondary outcomes included prevalence of comorbidities, the incidence of GI complications, sick leave, and joint replacements.

Results: The study included 189,553 patients with OA from Norway, 341,548 from Sweden, and 218,253 from Finland, 34.1% to 40.4% aged ≤ 60. About half of patients had NSAIDs dispensed before and after diagnosis, (Norway 56.6% and 48.6%; Sweden 50.1% and 44.0%; Finland 58.8% and 58.2%), compared to about one-fifth of the matches (Norway 19.1% and 18.5%; Sweden 12.7% and 12.2%; Finland 22.5% and 21.7%). NSAID use increased with age until approximately 55 years, then declined. After diagnosis, fewer patients had NSAID dispensations, but mean DDDs per prescription were generally higher. Secondary analyses showed a higher comorbidity burden, higher rates of GI complications, more sick leave days, and more joint replacements in patients with OA than in matched individuals.

Conclusion: Across Nordic countries, patients with OA had more NSAID dispensations, and GI complications were more prevalent compared to matched individuals. Notably, this was already evident in younger patients under the age of 60, underscoring the need for comprehensive GI risk assessment for every patient with OA. The substantial burden of OA was also evidenced by considerable numbers of sick leave days and joint replacements.

Introduction: This study aimed to investigate the effectiveness and safety of upadacitinib in patients with either oligo- or polyarticular active psoriatic arthritis (oPsA/pPsA) in routine clinical practice.

Methods: UPJOINT is a post-marketing, multicenter observational study in patients with active psoriatic arthritis (PsA), treated with upadacitinib according to local label over a period of 48 weeks. The decision for treatment initiation with upadacitinib was independent of the study participation. The study's denominated primary endpoint was the proportion of patients achieving minimal disease activity (MDA) at week 24 under continuous treatment with upadacitinib. Furthermore, maintenance of MDA response at week 48 among those who achieved response at week 24 was evaluated. Also, very low disease activity (VLDA), and improvement of the Disease Activity Index for Psoriatic Arthritis (DAPSA) in oPsA/pPsA were further composite outcomes of interest evaluated at baseline and weeks 4, 12, 24, 36, and 48 after treatment initiation. Safety data were collected in a separate dataset using standardized operating procedures regarding the documentation of adverse events, followed by MedDRA hierarchy categorization using system organ classes.

Results: A total of 364 patients were included in the effectiveness dataset for an as-observed analysis. The proportion of patients achieving MDA increased from 3.6% (overall) at baseline, 7.1% (oPsA), and 1.3% (pPsA) to 41.5% (overall), 55.8% (oPsA), and 32.0% (pPsA) at week 24, respectively. At week 48, 47.5% of the patients with oPsA and 35.1% of the patients with pPsA achieved MDA. The proportion of MDA responders increased noticeably as early as week 4 in both subgroups (oPsA 38.4%, pPsA 16.3%). The proportion of patients achieving VLDA and DAPSA remission increased from 0% for both outcomes at baseline in patients with oPsA and pPsA to 22.2% and 14.3% and 24.2% and 14.9%, respectively, at week 48. Altogether 127 (33.3%) patients experienced 213 adverse events (AEs) with a reasonable possibility of being related to the study drug. Forty-one serious AEs were reported in 26 patients (6.8%). From the categorized AEs of particular interest, infections were most common. However, in line with previous clinical studies, no new safety signals were identified.

Conclusion: Our data confirm that the effectiveness of upadacitinib in routine clinical practice is consistent with previous phase 3 trials for the treatment of active PsA, independent of the disease phenotype. Fast treatment effects reflected MDA achievement after 4 weeks of treatment in both PsA subgroups, similar to what is known from clinical studies.

Trial registration: NCT04758117 (ClinicalTrials.gov).

Introduction: The aim of this study was to evaluate guselkumab efficacy through week 100 in participants with psoriatic arthritis (PsA) and severe disease activity or patient global assessment (PtGA).

Methods: This post hoc analysis utilized DISCOVER-2 (NCT03158285) data from 739 biologic-naïve adults with active PsA (≥ 5 swollen/tender joints, C-reactive protein  ≥ 0.6 mg/dL) randomized to guselkumab every 4 weeks (Q4W) or at weeks 0 and 4, then every 8 weeks (Q8W); or placebo with crossover to guselkumab Q4W at week 24. Severe disease activity was defined as clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) > 27, Psoriatic Arthritis Disease Activity Score (PASDAS) ≥ 5.4, and PtGA Arthritis + Psoriasis ≥ 80 mm. Least squares mean (LSM) changes in cDAPSA, PASDAS, and PtGA were estimated with mixed models for repeated measures adjusted for baseline factors.

Results: Baseline characteristics among 648 (88%), 639 (86%), and 218 (29%) participants meeting the cDAPSA, PASDAS, and PtGA criteria for severe disease activity, respectively, were generally balanced across cohorts. LSM improvements from baseline with guselkumab Q4W/Q8W vs. placebo were -5.9 (p = 0.3905)/-7.2 (p = 0.0379) for cDAPSA at week 2; -1.5/-1.5 for PASDAS (both p < 0.0001); and -30.0/-32.1 for PtGA at week 8 (both p < 0.01). Differences vs. placebo increased through week 24 in the respective cohorts with guselkumab Q4W/Q8W: -9.8/-9.0, -1.1/-1.1, -24.0/-20.2 (all p < 0.0001). Through week 100 of guselkumab Q4W/Q8W treatment, LSM improvements of 69/74%, 52/54%, and 64/63% from baseline in cDAPSA (-35.9/-35.6), PASDAS (-3.6/-3.7), and PtGA (-56.8, -55.5), respectively, were observed. Regardless of severe disease activity definition, approximately 80% of guselkumab-randomized participants who achieved low disease activity at week 24 maintained this response at week 100.

Conclusion: In biologic-naïve participants with PsA and severe disease activity, guselkumab demonstrated early and durable clinically meaningful improvements in key PsA domains through 2 years.

Trial registration: ClinicalTrials.gov, NCT03158285.