Search

Background: Psoriatic arthritis (PsA) is a chronic inflammatory disease that causes pain and fatigue, reduces physical function, and negatively impacts health-related quality of life (HRQoL). In the phase III BE OPTIMAL and BE COMPLETE studies, bimekizumab demonstrated clinical efficacy and meaningful improvements in patient-reported outcome (PRO) measures in biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients, and those who had prior inadequate response/intolerance to tumor necrosis factor inhibitors (TNFi-IR). Objectives: To examine the association between achieving increasingly stringent clinical disease control criteria and improvements in PRO measures in patients with active PsA receiving bimekizumab. Design: Post hoc analysis of two phase III studies. Methods: BE OPTIMAL and BE COMPLETE assessed subcutaneous bimekizumab 160 mg every 4 weeks in bDMARD-naïve and TNFi-IR patients with active PsA. Disease control was assessed using American College of Rheumatology (ACR) response criteria, Minimal Disease Activity, Disease Activity Index for Psoriatic Arthritis, and the composite outcome of ACR50 and 100% improvement in Psoriasis Area and Severity Index. Associations between clinical disease control criteria and PRO measures of pain, fatigue, physical function, and HRQoL were assessed at week 16 and week 52/40 (BE OPTIMAL/BE COMPLETE). Results: Achievement of increasingly stringent clinical disease control criteria was generally associated with sequentially greater improvements in all PRO measures, including pain. At week 52/40, 94.7% of bDMARD-naïve and 97.6% of TNFi-IR patients achieving ACR70 reported ⩾50% improvements in pain from baseline, and the greatest numerical improvements (−48.5 bDMARD-naïve; −54.7 TNFi-IR). This pattern was evident as early as week 16 and sustained when assessed at week 52/40 across the majority of clinical disease control criteria and PRO measures reported. Conclusion: The achievement of increasingly stringent thresholds of disease control was associated with corresponding greater improvements in PROs, for patients receiving bimekizumab treatment, irrespective of prior TNFi use. Trial registration ClinicalTrials.gov: NCT03895203, NCT03896581, and NCT04009499. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess 52‐week efficacy and safety of bimekizumab in patients with active psoriatic arthritis (PsA) with or without concomitant methotrexate (+/−MTX) treatment at baseline. Methods: We conducted a post hoc analysis of patients in BE OPTIMAL (NCT03895203; biologic disease‐modifying antirheumatic drug [bDMARD]‐naïve), BE COMPLETE (NCT03896581; prior inadequate response or intolerance to tumor necrosis factor inhibitors [TNFi‐IR]), and the BE VITAL open‐label extension (NCT04009499) study. Patients were randomized to one of the following treatment groups: bimekizumab 160 mg every four weeks, placebo, or a reference drug (adalimumab 40 mg every two weeks; BE OPTIMAL only). From Week 16, placebo‐randomized patients received bimekizumab. Missing data were imputed using non‐responder imputation, multiple imputation, or worst‐category imputation. Results: Through Week 52, similar proportions of bimekizumab‐treated patients achieved American College of Rheumatology 50% (ACR50) response criteria for both +MTX and −MTX (BE OPTIMAL: 54.4% +MTX, 54.7% −MTX; BE COMPLETE: 56.3% +MTX, 48.0% −MTX). Similar proportions of bimekizumab‐treated patients achieved complete skin clearance (Psoriasis Area and Severity Index 100% [PASI100] response) and minimal disease activity in both +MTX and −MTX groups. Similar trends were seen in placebo/bimekizumab‐treated patients. Through Week 52, the proportion of bimekizumab‐treated patients with ≥1 treatment‐emergent adverse event were similar between the +MTX and −MTX groups (BE OPTIMAL 325 of 410 [79.3%] vs 230 of 292 [78.8%], BE COMPLETE 105 of 168 [62.5%] vs 138 of 220 [62.7%]). The safety profile was comparable between subgroups and consistent with the prior safety profile of bimekizumab. Conclusion: Treatment with bimekizumab demonstrated consistent, sustained efficacy to 52 weeks in bDMARD‐naïve and TNFi‐IR patients with PsA and was well tolerated, irrespective of concomitant MTX. [ABSTRACT FROM AUTHOR]

Objectives To evaluate 1-year bimekizumab efficacy in PsA from the patient perspective using the 12-item PsA Impact of Disease (PsAID-12) questionnaire. Methods BE OPTIMAL (NCT03895203; biologic DMARD [bDMARD]-naïve), BE COMPLETE (NCT03896581; inadequate response/intolerance to TNF inhibitors [TNFi-IR]) and BE VITAL (NCT04009499; open-label extension) assessed bimekizumab 160 mg every 4 weeks in patients with PsA. Post hoc analyses of patient-reported disease impact, assessed by the PsAID-12 questionnaire, are reported to 1 year (collected to Week 40 in BE COMPLETE). Results Overall, 1,112 total patients were included (698 bimekizumab, 414 placebo). Rapid improvements observed with bimekizumab treatment at Week 4 continued to Week 16 and were sustained to 1 year. At 1 year, mean (SE) change from baseline in PsAID-12 total score was comparable between bimekizumab-randomized patients and patients who switched to bimekizumab at Week 16 (bDMARD-naïve bimekizumab –2.3 [0.1], placebo/bimekizumab –2.2 [0.1]; TNFi-IR bimekizumab –2.5 [0.1], placebo/bimekizumab –2.2 [0.2]). Proportions of bimekizumab-randomized patients achieving clinically meaningful within-patient improvement (≥3-point decrease from baseline) at Week 16 were sustained to 1 year (bDMARD-naïve 49.0%; TNFi-IR 48.5%) and were similar for placebo/bimekizumab patients (bDMARD-naïve 44.4%; TNFi-IR 40.6%). Across studies and arms, 35.3% to 47.8% of patients had minimal or no symptom impact at 1 year. Improvements were observed to 1 year across all single-item domains, including pain, fatigue and skin problems. Conclusion Bimekizumab treatment resulted in rapid and sustained clinically meaningful improvements in disease impact up to 1 year in bDMARD-naïve and TNFi-IR patients with PsA. Trial registration BE OPTIMAL: NCT03895203; BE COMPLETE: NCT03896581; BE VITAL: NCT04009499 (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]

Objectives Evaluate effects of long-term bimekizumab treatment on patient-reported outcome (PRO) measures, symptoms and the impact of PsA on patients. Methods Patients with active PsA were enrolled into BE ACTIVE, a 48-week randomised controlled trial (NCT02969525). After Week 48, patients could enter a 104-week open-label extension (NCT03347110), receiving bimekizumab 160 mg every four weeks. PRO measures assessed included arthritis pain visual analogue scale (VAS), PsA Impact of Disease (PsAID)-9, 36-Item Short Form Survey (SF-36) and HAQ-Disability Index (HAQ-DI). Results were analysed as mean (S.E.M.) changes from baseline (CfB) from Week 0 to the end of the open-label extension (3 years) and as percentage of patients reaching patient-acceptable symptom state (PASS) for global impact (PsAID-9 total score ≤4) and normal function (HAQ-DI total score <0.5). Non-responder imputation was applied to missing binary outcomes. Results In 206 patients (mean age 49.3 years, 51.0% male), completion rate was high; 161 (78.2%) patients completed Week 152. Bimekizumab treatment was associated with long-term sustained improvements in pain [arthritis pain VAS CfB; Week 48: −29.9 (1.9); Week 152: −32.0 (1.9)] and fatigue [PsAID-9 fatigue CfB; −2.4 (0.2); −2.7 (0.2)]. High percentages of patients achieved acceptable symptom state (PsAID-9 PASS: 75.2%; 65.0%) and normalised function (HAQ-DI <0.5: 49.0%; 46.1%). Improvements in patient global assessment and SF-36 Physical Component Summary were also sustained. Conclusions Bimekizumab treatment was associated with long-term sustained improvements in pain and fatigue, reducing overall impact of PsA on patients. Physical function and quality of life improved up to 3 years. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT02969525, NCT03347110. [ABSTRACT FROM AUTHOR]

Mammalian cells have been used for reproduction of combinations prevalent in neurons and susceptible to alpha-dendrotoxin by means of Semliki Forest virus. Production of recombinant Kv1 alpha and beta subunits determined their oligomeric size.

Objective: To assess the longer-term impact of bimekizumab to 1 year on patient-reported symptoms, health-related quality of life (HRQoL), and work productivity in patients with active PsA who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve or had inadequate response/intolerance to tumor necrosis factor inhibitors (TNFi-IR) up to 1 year., Methods: BE OPTIMAL (NCT03895203; bDMARD-naïve) and BE COMPLETE (NCT03896581; TNFi-IR) are phase 3 studies of subcutaneous bimekizumab 160 mg every 4 weeks; both were double-blind and placebo-controlled to 16 weeks. Patients who completed Week 52 of BE OPTIMAL or Week 16 of BE COMPLETE were eligible for the open-label extension, BE VITAL (NCT04009499), during which all patients received bimekizumab. Patient-reported pain, fatigue, physical function, HRQoL, and work productivity are reported to Week 52/40 using individual study data for bimekizumab and placebo treatment arms., Results: Bimekizumab-randomized patients demonstrated sustained mean improvements from baseline in patient-reported outcomes to Week 52/40, including pain (Pain VAS [0-100]: bDMARD-naïve -30.5; TNFi-IR -31.8), fatigue (FACIT-Fatigue [0-52]: bDMARD-naïve 5.3; TNFi-IR 6.0), physical function (HAQ-DI [0-3]: bDMARD-naïve -0.34; TNFi-IR -0.39), and HRQoL (SF-36 PCS: bDMARD-naïve 8.1; TNFi-IR 8.4); placebo patients who switched to bimekizumab at Week 16 demonstrated comparable levels of improvement from Week 16 to 52/40. Improvements in overall work impairment were sustained among bimekizumab-randomized patients to Week 52. Similar trends were observed for absenteeism, presenteeism, and activity impairment., Conclusion: Bimekizumab treatment resulted in sustained improvements in patient-reported symptoms, HRQoL, and work productivity up to 1 year in bDMARD-naïve and TNFi-IR patients with active PsA.

Objective: To study the expression of small ubiquitin-like modifier 1 (SUMO-1) in aseptic loosening of prosthesis implants and to investigate its role in regulating the susceptibility of prosthesis-loosening fibroblast-like synoviocytes (FLS) to Fas-induced apoptosis., Methods: Specimens of aseptically loosened tissue were obtained at revision surgery, and the expression of SUMO-1 was analyzed by in situ hybridization. SUMO-1 levels in FLS were determined by quantitative polymerase chain reaction and Western blot analysis. Immunohistochemistry and confocal microscopy were used to study the subcellular localization of SUMO-1. The functional role of SUMO-1 in Fas-induced apoptosis of prosthesis-loosening FLS was investigated by small interfering RNA-mediated knockdown of SUMO-1 and by gene transfer of the nuclear SUMO-specific protease SENP1., Results: SUMO-1 was expressed strongly in aseptically loosened tissue and was found prominently at sites adjacent to bone. Prosthesis-loosening FLS expressed levels of SUMO-1 similar to the levels expressed by rheumatoid arthritis (RA) FLS, with SUMO-1 being found mainly in promyelocytic leukemia protein nuclear bodies. Knockdown of SUMO-1 had no effect on spontaneous apoptosis but significantly increased the susceptibility of prosthesis-loosening FLS to Fas-induced apoptosis. Gene transfer of the nuclear SUMO-specific protease SENP1 reverted the apoptosis-inhibiting effects of SUMO-1., Conclusion: These data suggest that SUMO-1 is involved in the activation of both RA FLS and prosthesis-loosening FLS by preventing these cells from undergoing apoptosis. Modification of nuclear proteins by SUMO-1 contributes to the antiapoptotic effects of SUMO-1 in prosthesis-loosening FLS, providing evidence for the specific activation of sumoylation during their differentiation. Therefore, SUMO-1 may be an interesting target for novel strategies to prevent aseptic prosthesis loosening.