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Objective: To assess the effect of bimekizumab on pain, morning stiffness, and fatigue in patients with nonradiographic and radiographic axial spondyloarthritis (axSpA) in the phase III BE MOBILE studies (ClinicalTrials.gov: NCT03928704 and NCT03928743)., Methods: Patients were randomized to bimekizumab 160 mg or placebo every 4 weeks; and all patients received bimekizumab from week 16. Patients reported spinal pain, peripheral pain, morning stiffness, and fatigue to week 52. Total and nocturnal spinal pain were each assessed on a 0-10 numerical rating scale (NRS). Individual Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) items (0-10-point NRS) assessed peripheral arthritis pain (question [Q] 3), enthesitis pain/discomfort (Q4), morning stiffness (mean of Q5 and Q6), and fatigue (Q1). Functional Assessment of Chronic Illness Therapy Fatigue subscale score (FACIT-Fatigue) is also reported., Results: At week 16, bimekizumab-treated patients reported lower mean nocturnal spinal pain, total spinal pain, and BASDAI scores (nominal except for nocturnal spinal pain; all P ≤ 0.001), as well as higher FACIT-Fatigue scores (nominal P < 0.05) vs placebo, indicating improved symptom levels. Improvements continued to week 52 in continuous bimekizumab-treated patients and in placebo-bimekizumab switchers. A higher proportion of bimekizumab- vs placebo-randomized patients achieved increasingly stringent thresholds for low spinal and peripheral pain at week 16; this was sustained or improved at week 52. Results were similar for morning stiffness and fatigue. At week 52, over half of patients were considered FACIT-Fatigue responders (≥ 8-point increase in score)., Conclusion: Bimekizumab treatment led to rapid improvements in levels of pain and morning stiffness. Substantial improvements were seen in all domains across the full disease spectrum of axSpA and continued to week 52.

Introduction: A matching-adjusted indirect comparison (MAIC) was conducted to assess the relative efficacy at 52 weeks (Wk52) of bimekizumab 160 mg every 4 weeks (Q4W) and ustekinumab 45 or 90 mg every 12 weeks (Q12W) in patients with psoriatic arthritis (PsA) who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or who had a previous inadequate response or an intolerance to tumor necrosis factor inhibitors (TNFi-IR)., Methods: Relevant trials were systematically identified. Individual patient data from the bimekizumab trials BE OPTIMAL (NCT03895203; N = 431) and BE COMPLETE (NCT03896581; N = 267) were matched with summary data on patients receiving ustekinumab in the PSUMMIT 1 trial (NCT01009086; 45 mg, N = 205; 90 mg; N = 204) and a subgroup of TNFi-IR patients receiving ustekinumab in the PSUMMIT 2 trial (NCT01077362; 45 mg, N = 60; 90 mg, N = 58), respectively. Patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of the ustekinumab trial patients. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Non-placebo-adjusted comparisons of recalculated bimekizumab and ustekinumab outcomes for the American College of Rheumatology (ACR) 20/50/70 response criteria (non-responder imputation) were analyzed., Results: In patients who were bDMARD naïve, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (odds ratio [95% confidence interval] 45 mg: 2.14 [1.35, 3.40]; 90 mg: 1.98 [1.24, 3.16]), ACR50 (45 mg: 2.74 [1.75, 4.29]; 90 mg: 2.29 [1.48, 3.55]), and ACR70 (45 mg: 3.33 [2.04, 5.46]; 90 mg: 3.05 [1.89, 4.91]). In patients who were TNFi-IR, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (45 mg: 4.17 [2.13, 8.16]; 90 mg: 4.19 [2.07, 8.49]), ACR50 (45 mg: 5.00 [2.26, 11.05]; 90 mg: 3.86 [1.70, 8.79]), and ACR70 (45 mg: 9.85 [2.79, 34.79]; 90 mg: 6.29 [1.98, 20.04])., Conclusions: Using MAIC, bimekizumab showed greater efficacy than ustekinumab in achieving all ACR responses in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52., Trial Registration: NCT03895203, NCT03896581, NCT01009086, NCT01077362., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Objectives: To assess impact of bimekizumab treatment on patient-reported outcomes and health-related quality of life (HRQoL) in patients with active psoriatic arthritis (PsA), using 16-week data from two phase 3 studies., Methods: BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug (bDMARD)-naïve) and BE COMPLETE (NCT03896581; tumour necrosis factor inhibitor inadequate response/intolerance (TNFi-IR)) are phase 3 studies of subcutaneous bimekizumab 160 mg Q4W; both were double-blind and placebo-controlled to 16 weeks. Patients were randomised 3:2:1 to bimekizumab, placebo or reference (subcutaneous adalimumab 40 mg Q2W) in BE OPTIMAL; 2:1 to bimekizumab or placebo in BE COMPLETE. Patient-reported outcomes for pain, fatigue, physical function and HRQoL are reported to week 16 using pooled and individual study data for bimekizumab and placebo patients., Results: 1073/1112 (96.5%) patients completed week 16 (bimekizumab:‍ 677/698 [97.0%]; placebo: 396/414 [95.7%]). Bimekizumab-treated patients achieved rapid improvements vs placebo in pain, fatigue, physical function and HRQoL by week 4, after a single dose. Improvements continued to week 16 for all patient-reported outcomes, including Pain Visual Analogue Scale (VAS; mean (95% CI) change from baseline: bimekizumab: -‍25.2 [-27.2, -23.1]; placebo:‍ -‍5.7 [-8.2, -3.3]) and FACIT-Fatigue (bimekizumab: 4.5 [3.9, 5.1]; placebo: 1.1 [0.3, 2.0]); both nominal p<0.001. Greater proportions of bimekizumab-treated patients achieved minimal clinically important differences for patient-reported symptoms vs placebo, including FACIT-Fatigue (bimekizumab: 53.1%; placebo: 36.3%) and HAQ-DI (bimekizumab:‍ 53.0%; placebo: 28.7%); both nominal p<0.001., Conclusion: Bimekizumab treatment demonstrated rapid and greater improvements in patient-reported pain, fatigue, physical function and HRQoL to week 16 vs placebo in bDMARD-naïve and TNFi-IR patients., Trial Registration Number: ClinicalTrials.gov: NCT03895203; NCT03896581., Competing Interests: Competing interests: MEH: Advisory board member and consultant for AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer and UCB. PJM: Research grants from AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB; consultancy fees from AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma and UCB; speakers’ bureau for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB. JFM: Affiliated with Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA at time of analysis; currently affiliated with UT Southwestern Medical Center, Dallas, TX, USA; consultant and/or investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma and UCB. WT: Research grants, consulting fees, speaking fees, and/or honoraria from AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer and UCB. NG, JC, JL: Employees and shareholders of UCB. BI: Employee of UCB; shareholder of AbbVie, GSK and UCB. VT: Employee of UCB. DDG: Consultant and/or received grant support from Abbvie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

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., (© 2024. The Author(s).)

Objectives: To understand the relative efficacy and safety of bimekizumab, a selective inhibitor of IL-17F in addition to IL-17A, vs other biologic and targeted synthetic DMARDs (b/tsDMARDs) for PsA using network meta-analysis (NMA)., Methods: A systematic literature review (most recent update conducted on 1 January 2023) identified randomized controlled trials (RCTs) of b/tsDMARDs in PsA. Bayesian NMAs were conducted for efficacy outcomes at Weeks 12-24 for b/tsDMARD-naïve and TNF inhibitor (TNFi)-experienced patients. Safety at Weeks 12-24 was analysed in a mixed population. Odds ratios (ORs) and differences of mean change with the associated 95% credible interval (CrI) were calculated for the best-fitting models, and the surface under the cumulative ranking curve (SUCRA) values were calculated to determine relative rank., Results: The NMA included 41 RCTs for 22 b/tsDMARDs. For minimal disease activity (MDA), bimekizumab ranked 1st in b/tsDMARD-naïve patients and 2nd in TNFi-experienced patients. In b/tsDMARD-naïve patients, bimekizumab ranked 6th, 5th and 3rd for ACR response ACR20/50/70, respectively. In TNFi-experienced patients, bimekizumab ranked 1st, 2nd and 1st for ACR20/50/70, respectively. For Psoriasis Area and Severity Index 90/100, bimekizumab ranked 2nd and 1st in b/tsDMARD-naïve patients, respectively, and 1st and 2nd in TNFi-experienced patients, respectively. Bimekizumab was comparable to b/tsDMARDs for serious adverse events., Conclusion: Bimekizumab ranked favourably among b/tsDMARDs for efficacy on joint, skin and MDA outcomes, and showed comparable safety, suggesting it may be a beneficial treatment option for patients with PsA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To assess the impact of bimekizumab on physical functioning, sleep, work productivity and overall health-related quality of life (HRQoL) in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) in the phase 3 studies BE MOBILE 1 and 2., Methods: Patients were randomised to subcutaneous bimekizumab 160 mg or placebo every 4 weeks; from Week 16, all patients received bimekizumab 160 mg every 4 weeks. We report the following outcomes to Week 52: Bath Ankylosing Spondylitis Functional Index (BASFI), Medical Outcomes Study Sleep Scale Revised (MOS-Sleep-R) Index II, Work Productivity and Activity Impairment: axSpA (WPAI:axSpA), Short Form-36 Physical and Mental Component Summary (SF-36 PCS/MCS) and Ankylosing Spondylitis Quality of Life (ASQoL)., Results: At Week 16, bimekizumab-randomised patients demonstrated significantly greater improvement from baseline versus placebo in BASFI, SF-36 PCS and ASQoL (p<0.001), and numerically greater improvements in MOS-Sleep-R Index II and WPAI:axSpA scores. Higher proportions of bimekizumab-randomised versus placebo-randomised patients at Week 16 achieved increasingly stringent thresholds for improvements in BASFI (0 to ≤4), and thresholds for meaningful improvements in SF-36 PCS (≥5-point increase from baseline) and ASQoL (≥4-point decrease from baseline). Responses were sustained or further improved to Week 52, where 60%-70% of bimekizumab-treated patients achieved BASFI ≤4 and meaningful improvements in SF-36 PCS and ASQoL, regardless of whether originally randomised to bimekizumab or placebo., Conclusion: Bimekizumab treatment led to early improvements in physical function, sleep, work productivity and overall HRQoL at Week 16 in patients across the full axSpA disease spectrum. Improvements were sustained to Week 52., Trial Registration Numbers: NCT03928704; NCT03928743., Competing Interests: Competing interests: MD: Educational grant from Pfizer paid to institution; consulting fees (eg, advisory boards) from Amgen and UCB Pharma; VN-C: Speakers bureau for AbbVie, Eli Lilly, Fresenius Kabi, Janssen, MSD, Novartis, Pfizer and UCB Pharma; consultant for AbbVie, Eli Lilly, Galapagos, MoonLake, MSD, Novartis, Pfizer and UCB Pharma; grant/research support from AbbVie and Novartis; AB: Research grants from AbbVie; speakers honoraria and consultation fees from AbbVie, Galapagos, Pfizer, Novartis and UCB Pharma; KG: Speakers bureau for AbbVie, Eli Lilly, Novartis and UCB Pharma; consultant for AbbVie, Eli Lilly, Novartis and UCB Pharma; grant/research support from AbbVie, Gilead, Eli Lilly, Novartis and UCB Pharma; LSG: Grants from Novartis and UCB Pharma paid to institution; consulting fees from AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer and UCB Pharma; CdlL: Consultant to UCB Pharma; TV, UM and MFM: Employees of UCB Pharma; CF and VT: Employees and shareholders of UCB Pharma; AD: Speakers bureau for Janssen, Novartis, and Pfizer; consultant for AbbVie, BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma; grant/research support from AbbVie, BMS, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer and UCB Pharma; MR: Speakers bureau for AbbVie, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; consultant of AbbVie, Eli Lilly, Novartis and UCB Pharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Matching-adjusted indirect comparisons (MAIC) were used to assess the relative efficacy of bimekizumab 160 mg every 4 weeks (Q4W) compared to guselkumab 100 mg Q4W or every 8 weeks (Q8W) at 48/52 weeks in patients with psoriatic arthritis (PsA) who were biologic disease-modifying antirheumatic drug-naïve (bDMARD-naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR)., Methods: Relevant trials were identified as part of a systematic literature review. For patients who were bDMARD-naïve, individual patient data (IPD) from BE OPTIMAL (N = 431) was matched to summary data from DISCOVER-2 (Q4W, n = 245; Q8W, n = 248). For patients who were TNFi-IR, IPD from BE COMPLETE (n = 267) and summary data from COSMOS (Q8W, N = 189). Trial populations were re-weighted using propensity scores. Unanchored comparisons of recalculated bimekizumab and guselkumab 48- or 52-week non-responder imputation outcomes for 20/50/70% improvement in American College of Rheumatology score (ACR20/50/70) and minimal disease activity (MDA) index were analyzed., Results: In patients who were bDMARD-naïve, bimekizumab was associated with a greater likelihood of ACR50 (odds ratio [95% confidence interval] 1.62 [1.07, 2.44]; p = 0.021), ACR70 (2.20 [1.43, 3.38]; p < 0.001), and MDA (1.82 [1.20, 2.76]; p = 0.005) compared to guselkumab Q4W at week 52. Bimekizumab also had a greater likelihood of ACR70 response (2.08 [1.34, 3.22]; p = 0.001) and MDA (2.07 [1.35, 3.17]; p < 0.001) compared to guselkumab Q8W at week 52. In patients who were TNFi-IR, bimekizumab had a greater likelihood in achieving all evaluated outcomes compared to guselkumab Q8W at week 48/52 (ACR20, 1.77 [1.15, 2.72]; p = 0.010; ACR50, 1.56 [1.03, 2.36]; p = 0.037; ACR70, 1.66 [1.05, 2.61]; p = 0.028; and MDA, 1.95 [1.27, 3.02]; p = 0.003)., Conclusions: According to MAICs, bimekizumab demonstrated greater or comparable efficacy on ACR50/70 and MDA outcomes than guselkumab in patients with PsA who were bDMARD-naïve and TNFi-IR at week 48/52. Bimekizumab had a more favorable likelihood than guselkumab in achieving more stringent treatment outcomes., Trial Registrations: NCT03895203, NCT03896581, NCT04009499, NCT03158285, NCT03796858., (© 2024. The Author(s).)

Introduction: Matching-adjusted indirect comparisons (MAICs) were used to compare the efficacy of bimekizumab and secukinumab 150 mg and 300 mg at 52 weeks for the treatment of psoriatic arthritis (PsA) in patients 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)., Methods: Relevant trials were systematically identified. Individual patient data from bimekizumab randomized controlled trials, BE OPTIMAL (N = 431) and BE COMPLETE (N = 267), were matched to aggregate data from bDMARD-naïve and TNFi-IR patient subgroups from FUTURE 2 using secukinumab 150 mg and 300 mg doses (bDMARD-naïve: N = 63/37; TNFi-IR: N = 67/33). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of patients in the secukinumab trials. Unanchored comparisons of recalculated bimekizumab and secukinumab 52-week non-responder imputation outcomes for 20/50/70% improvement in American College of Rheumatology score (ACR20/50/70) and minimal disease activity (MDA) index were analyzed., Results: In patients who were bDMARD-naïve, bimekizumab had a greater likelihood of ACR70 response than secukinumab 150 mg (odds ratio [95% confidence interval] 2.39 [1.26, 4.53]; p = 0.008) and secukinumab 300 mg (2.03 [1.11, 3.72]; p = 0.021) at 52 weeks. In patients who were TNFi-IR, bimekizumab had a greater likelihood of response compared to secukinumab 150 mg for ACR20 (3.50 [1.64-7.49]; p = 0.001), ACR50 (3.32 [1.41, 7.80]; p = 0.006), ACR70 (2.95 [1.08, 8.07]; p = 0.035) and MDA (3.52 [1.38, 8.99]; p = 0.009), and a greater likelihood of response compared to secukinumab 300 mg for ACR50 (2.44 [1.06, 5.65]; p = 0.037) and MDA (2.92 [1.20, 7.09]; p = 0.018) at 52 weeks., Conclusion: In this MAIC analysis, the efficacy of bimekizumab, as demonstrated by the likelihood of ACR20/50/70 and MDA response at 52 weeks, was greater or comparable to secukinumab 150 mg and 300 mg for patients with PsA who were bDMARD-naïve and TNFi-IR., Trial Registration Numbers: NCT03895203, NCT03896581, NCT04009499, NCT01752634, NCT01989468, NCT02294227, NCT02404350., (© 2024. The Author(s).)

Objectives: To compare the efficacy and safety of bimekizumab 160 mg every 4 weeks, a selective inhibitor of IL-17F and IL-17A, with those of biologic/targeted synthetic DMARDs (b/tsDMARDs) in non-radiographic axial SpA (nr-axSpA) and AS., Methods: A systematic literature review identified randomized controlled trials until January 2023 for inclusion in Bayesian network meta-analyses (NMAs), including three b/tsDMARDs exposure networks: predominantly-naïve, naïve, and experienced. Outcomes were Assessment of SpondyloArthritis international Society (ASAS)20, ASAS40 and ASAS partial remission (PR) response rates at 12-16 weeks. A safety NMA investigated discontinuations due to any reason and serious adverse events at 12-16 weeks., Results: The NMA included 36 trials. The predominantly-naïve network provided the most comprehensive results. In the predominantly-naïve nr-axSpA analysis, bimekizumab had significantly higher ASAS20 response rates vs secukinumab 150 mg [with loading dose (LD)/without LD], and comparable response rates vs other active comparators. In the predominantly-naïve AS analysis, bimekizumab had significantly higher ASAS40 response rates vs secukinumab 150 mg (without LD), significantly higher ASAS-PR response rates vs secukinumab 150 mg (with LD) and comparable response rates vs other active comparators. Bimekizumab demonstrated similar safety to that of other b/tsDMARDs., Conclusion: Across ASAS outcomes, bimekizumab was comparable with most b/tsDMARDs, including ixekizumab, TNF inhibitors and upadacitinib, and achieved higher response rates vs secukinumab for some ASAS outcomes in predominantly b/tsDMARD-naïve nr-axSpA and AS patients at 12-16 weeks. In a pooled axSpA network, bimekizumab demonstrated comparable safety vs other b/tsDMARDs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To assess how achievement of increasingly stringent clinical response criteria and disease activity states at week 52 translate into changes in core domains in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA)., Methods: Patients in BE MOBILE 1 and 2 achieving different levels of response or disease activity (Assessment of SpondyloArthritis International Society (ASAS) and Ankylosing Spondylitis Disease Activity Score (ASDAS) response criteria, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50)) at week 52 were pooled, regardless of treatment arm. Associations between achievement of these endpoints and change from baseline (CfB) in patient-reported outcomes (PROs) measuring core axSpA domains, including pain, fatigue, physical function, overall functioning and health, and work and employment, were assessed., Results: Achievement of increasingly stringent clinical efficacy endpoints at week 52 was generally associated with sequentially greater improvements from baseline in all PROs. Patients with nr-axSpA achieving ASAS40 demonstrated greater improvements (CfB) than patients who did not achieve ASAS40 but did achieve ASAS20, in total spinal pain (-5.3 vs -2.8, respectively), Functional Assessment of Chronic Illness-Fatigue subscale (12.7 vs 6.7), Bath Ankylosing Spondylitis Function Index (-3.9 vs -1.8), European Quality of Life 5-Dimension 3-Level Version (0.30 vs 0.16), Work Productivity and Activity Impairment-axSpA presenteeism (-35.4 vs -15.9), overall work impairment (-36.5 vs -12.9), activity impairment (-39.0 vs -21.0) and sleep (9.0 vs 3.9). Results were similar for ASDAS and BASDAI50. Similar amplitudes of improvement were observed between patients with nr-axSpA and r-axSpA., Conclusions: Patients treated with bimekizumab across the full axSpA disease spectrum, who achieved increasingly stringent clinical response criteria and lower disease activity at week 52, reported larger improvements in core axSpA domains., Competing Interests: Competing interests: VN-C: Speakers’ bureau for AbbVie, Eli Lilly, Fresenius Kabi, Janssen, MSD, Novartis, Pfizer and UCB Pharma; consultant for AbbVie, Eli Lilly, Galapagos, MoonLake, MSD, Novartis, Pfizer and UCB Pharma; grant/research support from AbbVie and Novartis; SR: Grants from AbbVie, Galapagos, MSD, Novartis, Pfizer and UCB Pharma; consultancy from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi and UCB Pharma; AD: Speakers’ bureau for Janssen, Novartis and Pfizer; consultant for AbbVie, BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB Pharma; grant/research support from AbbVie, BMS, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer, and UCB Pharma; PJM: Research grants from AbbVie, Acelyrin, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma; consultancy fees from AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma, Takeda, UCB Pharma, and Ventyx; speakers’ bureau for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; MR: Speakers’ bureau for AbbVie, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; consultant of AbbVie, Eli Lilly, Novartis and UCB Pharma; CdlL: Consultant to UCB Pharma; CF, VT: Employees and shareholders of UCB Pharma; MFM, UM: Employees of UCB Pharma; JK: Consulting fees from Alvotech Swiss AG, Boehringer Ingelheim GmbH, Organon, Ridgeline Discovery, Scipher Medicine, Samsung Bioepis, Sandoz and UCB Pharma; grant/research support paid to institution from Gilead and Novartis; MM: Consultancy fees from AbbVie, BMS, Eli Lilly, Novartis, Pfizer and UCB Pharma; research grants from AbbVie, BMS and UCB Pharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Capacity to work is impacted by psoriatic arthritis (PsA). Our objective was to describe the course of work productivity and leisure activity in patients with PsA treated with biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs)., Methods: A systematic literature review identified all trials and observational studies published January 1, 2010-October 22, 2021, reporting work productivity using the Work Productivity and Activity Impairment Questionnaire (WPAI) in patients with PsA treated with b/tsDMARDs. Outcomes for WPAI domains (absenteeism, presenteeism, total work productivity, and activity impairment) were collected at baseline and time point closest to 24 weeks of treatment. A random effects meta-analysis of single means was conducted to calculate an overall absolute mean change from baseline for each WPAI domain., Results: Twelve studies (ten randomized controlled and two observational) assessing patients treated with adalimumab, bimekizumab, guselkumab, ixekizumab, risankizumab, secukinumab, or upadacitinib were analysed. Among 3741 employed patients, overall mean baseline scores were 11.4%, 38.7%, 42.7%, and 48.9% for absenteeism, presenteeism, total work productivity impairment, and activity impairment, respectively. Estimated absolute mean improvements (95% confidence interval) to week 24 were 2.4 percentage points (%p) (0.6, 4.1), 17.8%p (16.2,19.3), 17.6%p (15.9,19.4), and 19.3%p (17.6, 21.0) respectively, leading to a mean relative improvement of 41% for total work productivity. The change in work outcomes in the b/tsDMARDs appeared similar., Conclusions: This systematic literature review and meta-analysis confirmed that patients with active PsA have a substantially reduced capacity to work and participate in leisure activities. Substantial improvements across various WPAI domains were noted after 24 weeks of b/tsDMARD treatment, especially in presenteeism, total work productivity, and activity impairment. These findings may be useful for reimbursement purposes and in the context of shared decision-making. This systematic literature review (SLR) of randomized clinical trials and observational studies of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs b/tsDMARDs in patients with PsA found that at treatment introduction, patients presented with a 42.7% mean productivity loss per week as assessed by the Work Productivity and Activity Impairment (WPAI) Questionnaire. Through a meta-analysis comparing before/after values without adjustment for placebo response, we found that after 24 weeks of treatment with b/tsDMARDs, there was a mean absolute improvement of 17.6 percentage points and a mean relative improvement of 41% in total work productivity, with similar magnitudes of improvement in time spent at work and regular activities outside of work. These results provide clinical-, regulatory- and reimbursement decision-makers with data on the potential societal and socio-economic benefits of b/tsDMARDs in PsA., (© 2024. The Author(s).)

Objectives: To investigate psychometric performance of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) total and individual item scores in patients with psoriatic arthritis (PsA) and to estimate score change thresholds and scores corresponding to different levels of symptom/impact severity., Methods: Data up to week 16 from 1252 patients with active PsA enrolled in two randomised controlled trials of bimekizumab (BE OPTIMAL (NCT03895203) and BE COMPLETE (NCT03896581)) were used to assess construct validity (correlations with other patient-reported outcomes), known-groups validity (based on Minimal Disease Activity index, Disease Activity Index for Psoriatic Arthritis and Psoriatic Arthritis Disease Activity Score), reliability (Cronbach's alpha and intraclass correlation coefficients (ICCs)) and responsiveness (sensitivity to change). Clinically meaningful within-patient improvement thresholds were estimated by anchor-based and distribution-based analyses, and symptom/impact severity thresholds were estimated by receiver operating characteristic curve analyses., Results: The mean (SD) PsAID-12 total score at baseline was 4.19 (1.94). PsAID-12 scores demonstrated good convergent validity and good known-groups validity. Internal consistency reliability (Cronbach's alpha 0.95) and test-retest reliability (ICC ≥ 0.70) were also good. Responsiveness was acceptable (correlations ≥0.30 for most scores). Improvement thresholds were estimated at 1.5-2 points for the PsAID-12 total score and 2 or 3 points for item scores. Thresholds for different levels of symptom/impact severity could be derived for most PsAID-12 items., Conclusions: The PsAID-12 demonstrated robust psychometric properties in a large sample of patients with active PsA, supporting its use as a fit-for-purpose patient-reported outcome in this population. Furthermore, thresholds for score interpretation were derived., Competing Interests: Competing interests: LG: Grants from AbbVie, Biogen, Eli Lilly, Novartis, Sandoz and UCB Pharma; consulting fees from AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Sandoz and UCB Pharma. A-MO: Research grants to Johns Hopkins University from AbbVie, Amgen and Janssen; consulting fees from BMS, Janssen, Sanofi and UCB Pharma. LCC: Grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma; consultant for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake Pharma, Novartis, Pfizer, and UCB Pharma; speaking fees from AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, medac, Novartis, Pfizer, and UCB Pharma. DG: Consultant and/or received grant support from Abbvie, Amgen, BMS, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB Pharma. AO: Grant/research support from AbbVie, Amgen, Janssen, Novartis and Pfizer, consultant of AbbVie, Amgen, BMS, Celgene, CorEvitas, Eli Lilly, GSK, Gilead, Janssen, Novartis, Pfizer, Takeda and UCB Pharma. CGP: Employed by Evidera, a part of Thermo Fisher Scientific, which received funding for this research from UCB Pharma. VC, VT and JL: Employees and stockholders of UCB Pharma. BI: Employee of UCB Pharma; shareholder of AbbVie, GlaxoSmithKline and UCB Pharma. MdW: Over the last five years Stichting Tools has received fees for lectures or consultancy provided by MdW from Celgene, Eli Lilly, Janssen-Cilag, Pfizer and UCB Pharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To estimate the cost-effectiveness of a treatment-pathway initiated with bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with axial spondyloarthritis (axSpA) compared with IL-17Ai's, ixekizumab, and secukinumab, from the NHS Scotland perspective., Methods: The axSpA treatment-pathway was modeled using a decision tree followed by a lifetime Markov model. The pathway included first- and second-line biologic disease-modifying antirheumatic drugs (bDMARD), followed by best supportive care (bDMARD, nonbiologic). Bimekizumab followed by any bDMARD ("BKZ") was compared with IL-17Ai's: secukinumab 150 mg followed by a blend ("SEC") of dose up-titration to secukinumab 300 mg and any bDMARD, or ixekizumab followed by any bDMARD ("IXE"). Transition to the next therapy was triggered by Bath Ankylosing Spondylitis Disease Activity Index-50% (BASDAI50) non-response or any-cause discontinuation. A published network meta-analysis provided efficacy data. EuroQoL-5-dimensions utilities were derived by mapping from Ankylosing Spondylitis Disease Activity Score. Costs included disease management (linked to functional limitations), biologics acquisition (list prices), administration and monitoring (NHS 2021/22). Discounting was 3.5%/year. Probabilistic results from patients with non-radiographic axSpA and ankylosing spondylitis were averaged to reflect the axSpA disease spectrum. Scenario and sensitivity analyses were performed., Results: The incremental cost-effectiveness ratio (ICER) of BKZ was £24,801/quality-adjusted life-year (QALY) vs. SEC (95% credible interval £24,163-£25,895). BKZ had similar costs (Δ -£385 [-£15,239-£14,468]) and QALYs (Δ 0.039 [-0.748-0.825]) to IXE, with £1,523 (£862-£2,222) net monetary benefit. Conclusions remained unchanged in most scenarios. Results' drivers included BASDAI50 response rate and disease management cost., Limitations: Results were based on list prices. Data concerning up-titration to secukinumab 300 mg was scarce., Conclusions: The bimekizumab treatment-pathway represents a cost-effective option across the axSpA disease spectrum in Scotland. Bimekizumab is cost-effective compared to a secukinumab-pathway that includes dose up-titration, and has similar costs and QALYs to an ixekizumab-pathway.

Background: Axial spondyloarthritis (axSpA) can limit work participation. Our objective was to characterise productivity in patients with axSpA, including changes after 12-16 weeks of treatment with biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs)., Methods: A systematic literature review identified studies published from 1 January 2010 to 21 October 2021 reporting work productivity using the Work Productivity and Activity Impairment (WPAI) questionnaire in patients with axSpA initiating b/tsDMARDs. Baseline and Week 12-16 overall work productivity, absenteeism, presenteeism and activity impairment scores were used in a random-effects meta-analysis to calculate absolute mean change from baseline for each WPAI-domain., Results: Eleven studies in patients with axSpA who received either placebo (n=727) or treatment with adalimumab, bimekizumab, etanercept, ixekizumab, secukinumab or tofacitinib (n=994) were included. In working patients initiating a b/tsDMARD, mean baseline overall work productivity impairment, absenteeism and presenteeism scores were 52.1% (N=7 studies), 11.0% and 48.8% (N=6 studies), respectively. At Week 12-16, the pooled mean change from baseline in overall work impairment for b/tsDMARDs or placebo was -21.6% and -12.3%. When results were extrapolated to 1 year, the potential annual reductions in cost of paid and unpaid productivity loss per patient ranged from €11 962.88 to €14 293.54., Conclusions: Over 50% of employed patients with active axSpA experienced work impairment, primarily due to presenteeism. Overall work productivity improved at Weeks 12-16 to a greater extent for patients who received b/tsDMARDs than placebo. Work productivity loss was associated with a substantial cost burden, which was reduced with improvements in impairment., Competing Interests: Competing interests: MR: Consultant to UCB Pharma; Speakers bureau from AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; consultant of AbbVie, Eli Lilly, Novartis and UCB Pharma. MFM: Employee of UCB Pharma. DW and VT: Employees and stockholders of UCB Pharma. BH and N-EZ: Employees of Cytel, which served as a consultant on the project (at the time of research). AB: Received departmental research grants from AbbVie and consulting fees or honorarium from Galapagos, Hy2Care and Novartis., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with active axial spondyloarthritis (axSpA) exhibit more absences and lower levels of productivity in the workplace and household than the general population, which can improve upon treatment., Objectives: The objective of this study is to determine the long-term impact of achieving different levels of clinical response or disease activity on workplace and household productivity in patients with axSpA., Design: RAPID-axSpA (NCT01087762) was a 204-week phase III trial evaluating the safety and efficacy of certolizumab pegol (CZP) in adult patients with active axSpA., Methods: The impact of axSpA on workplace and household productivity was evaluated using the validated arthritis-specific Work Productivity Survey. Outcomes included the percentage of patients achieving Assessment of SpondyloArthritis International Society (ASAS) response and Ankylosing Spondylitis Disease Activity Score (ASDAS) thresholds. This post hoc study used a generalised estimating equations model to determine the association between the threshold of clinical response achieved and patient productivity., Results: Of 218 CZP-randomised patients, 65.1% completed week 204. At baseline, 72.0% were employed outside the home. Of the patients who were unemployed, 42.6% were unable to work due to arthritis. Achievement of higher treatment response thresholds, such as clinical remission, was associated with fewer days affected by workplace absenteeism (ASAS-partial remission: 4.0 days, ASAS40: 8.6 days, ASAS20 but not reaching ASAS40 response: 29.4 days, ASAS20 non-response: 69.2 days; ASDAS-inactive disease: 5.0 days, ASDAS-low disease activity: 15.6 days, ASDAS-high disease activity: 32.7 days, ASDAS-very high disease activity: 93.4 days). Similar associations were found for workplace presenteeism, and household absenteeism and presenteeism., Conclusions: Over 4 years, achievement of higher clinical response thresholds and lower levels of disease activity was associated with fewer cumulative days affected by absenteeism or presenteeism, with clinical remission associated with the greatest improvements in productivity. This highlights the importance of targeting these thresholds to limit the burden of axSpA on society and on patients' daily lives., Competing Interests: M.R. has received speaking fees from AbbVie, BMS, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; is a consultant for AbbVie, Eli Lilly, Novartis and UCB Pharma. P.M.M. has received personal fees from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB Pharma; is a consultant for AbbVie, Amgen, Eli Lilly, Janssen, Merck, Novartis and UCB Pharma. V.T. is an employee of UCB Pharma. N.d.P. is an employee of UCB Pharma. B.H. is an employee and stockholder of UCB Pharma. L.S.G. has received grants from Novartis and UCB Pharma, paid to institution; has received consulting fees from AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer and UCB Pharma., (© The Author(s), 2023.)

Background: Psoriatic arthritis (PsA) impacts the physical health and functional ability of patients, leading to reduced productivity. High unemployment rates and absence due to sickness have been reported in patients with PsA., Objectives: This post hoc study investigated certolizumab pegol treatment impact on workplace and household productivity in patients with PsA, and assessed whether achievement of more stringent disease control was associated with greater improvements in productivity., Design: RAPID-PsA was a 216-week phase III trial., Methods: This post hoc study used a generalised estimating equations (GEE) model to examine the disease activity association, measured using American College of Rheumatology (ACR) and Disease Activity in PSoriatic Arthritis (DAPSA), and workplace and household productivity, assessed using an arthritis-specific Work Productivity Survey (WPS). The GEE model estimated the mean cumulative number of days patients meeting different disease control criteria were affected by absenteeism or presenteeism in the workplace and household., Results: In all, 273 patients were randomised to certolizumab pegol and 183 (67.0%) completed Week 216. At baseline, 60.8% of patients were employed outside the home. Improved disease control, measured using ACR and DAPSA criteria, was associated with fewer cumulative days affected by workplace absenteeism through Week 216: ACR70: 4.1 days, ACR50 to <70: 7.7, ACR20 to <50: 20.9,

Objective: The impact of the COVID-19 pandemic on patients with inflammatory rheumatic diseases, such as ankylosing spondylitis (AS), has been variable. Here, we assess disease activity and health-related quality of life (HRQoL) through the pandemic in patients with AS., Methods: In the open-label extension (OLE) of the phase 2b BE AGILE study, patients with AS received 160 mg of subcutaneous bimekizumab every 4 weeks. We assessed Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Quality of Life (ASQoL) scores in the OLE immediately before and during the COVID-19 pandemic (September 2019 to April 2021)., Results: A total of 232 patients remained in the BE AGILE OLE and were included in this post hoc study at the start of the analysis period (September 1, 2019); 12 patients had a COVID-19 treatment-emergent adverse event, and no cases resulted in death. The number of missed bimekizumab doses due to COVID-19 (11 doses) was minimal, and missed assessments remained low (≤5%) compared with the prepandemic period. Mean ASDAS-CRP (1.8), BASDAI (2.4), and ASQoL scores (2.8) in the OLE were low at pre-pandemic baseline and remained stable at 1.7 to 1.8, 2.2 to 2.4, and 2.0 to 2.8, respectively, across successive 3-month periods immediately before and during the pandemic. ASDAS-CRP, BASDAI, and ASQoL stability was consistent across major study countries., Conclusion: Disease activity and HRQoL remained stable during the COVID-19 pandemic in patients with AS receiving bimekizumab in the BE AGILE OLE, with no indication of negative effects on these outcomes., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Introduction: Biologic treatments are increasingly being used in the management of moderate to severe plaque psoriasis (PSO). Bimekizumab is a selective inhibitor of both interleukin (IL)-17A and IL-17F approved for the treatment of moderate to severe PSO. Although bimekizumab trials provide comparisons to secukinumab, adalimumab and ustekinumab, there are no further head-to-head comparisons of bimekizumab to other biologics. This network meta-analysis (NMA) aimed to compare the short-term efficacy of bimekizumab versus other biologic systemic therapies for moderate to severe PSO., Methods: A systematic literature review was conducted to identify randomised controlled trials (RCTs) in patients with moderate to severe PSO. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Database of Systematic Reviews and PsycINFO were searched on July 1, 2020. An enhanced multinomial Bayesian NMA model was used to evaluate the comparative efficacy in 50%, 75%, 90% and 100% improvement from baseline Psoriasis Area and Severity Index (PASI 50/75/90/100) at 10-16 weeks. The model was also adjusted for baseline risk, given the variable placebo responses across the trials., Results: Eighty-six RCTs (including 34,476 patients) were included in the NMA. IL-17 and IL-23 inhibitors were the most effective treatments across all PASI levels. At 10-16 weeks, bimekizumab had the highest probability of achieving PASI 75 (92.3%), PASI 90 (84.0%) and PASI 100 (57.8%). Bimekizumab demonstrated statistical superiority over all biologics in achieving PASI 90 and PASI 100 thresholds. For PASI 75, the benefit of bimekizumab was statistically significant compared to all other treatments except risankizumab and ixekizumab., Conclusion: This analysis demonstrated that IL-17 and IL-23 inhibitors were highly effective in achieving short-term improvement among patients with moderate to severe PSO. Patients receiving bimekizumab were significantly more likely to achieve PASI 90 or PASI 100 within 10-16 weeks of the first injection than all other biologics., (© 2022. The Author(s).)

Background: Symptoms of neurogenic orthostatic hypotension (nOH), including lightheadedness/dizziness, presyncope, syncope, and falls, can lead to impaired functional ability and reduced quality of life. Because the severity and frequency of nOH symptoms fluctuate, it may be difficult for patients to accurately quantify the effect of symptoms on their daily lives using available outcome measures. A new single-item instrument, the 'Good Day Bad Day,' was developed, and its psychometric validity was assessed in patients with nOH., Methods: Data from a 6-month, prospective, observational cohort study of patients with nOH who were newly initiating droxidopa treatment were used. Patients were asked to quantify the number of good and bad days in the previous 7 days and responded to other validated patient-reported outcomes instruments. The concurrent and discriminant validities and the stability of the Good Day Bad Day instrument were assessed., Results: A total of 153 patients were included in the analysis (mean [SD] age, 62.3 [17] years). Change in the number of good days moderately correlated with improvements in other patient-reported outcomes (rho value range, -0.38 to -0.61). When data were examined categorically (low vs high symptom severity), the mean number of good days was higher in subgroups representing low symptom severity across measures at 1, 3, and 6 months (all P ≤ 0.01)., Conclusions: The Good Day Bad Day instrument provided good discrimination at baseline and over time and may aid in assessment of the effects of nOH symptoms on patients., Competing Interests: CF is an employee of Creativ-Ceutical, was formerly employed by Lundbeck, and is a shareholder of Lundbeck. RM is an employee of Creativ-Ceutical, and NG and VT were employees of Creativ-Ceutical at the time of the validation analyses. LAH and SK are employees of Lundbeck. This work was supported by Lundbeck; the data reported were derived from a study that was supported by Lundbeck. The sponsor participated in the design of this study, data analysis and interpretation, and in the preparation of the manuscript., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Over the past decade, several drugs have been approved for the treatment of relapsed or refractory multiple myeloma (RRMM). This retrospective study, using the French National Healthcare database (SNDS), describes the treatment patterns and outcomes of patients with RRMM treated in real-world clinical practice in France. Patients were adults, with a diagnosis of multiple myeloma, who initiated second-line (2L) treatment approved for use in France between 2014 and 2018; this included bortezomib, carfilzomib, daratumumab, ixazomib, lenalidomide, or pomalidomide. Data were analyzed overall, by first-line (1L) autologous stem cell transplant (ASCT) status and by lenalidomide treatment status at 2L. In total, 12987 patients with RRMM were included in the study (mean age 69.5 years); 27% received an ASCT at 1L, and 30% received a lenalidomide-sparing regimen at 2L. Overall, and among the ASCT and non-ASCT subgroups, most patients received a bortezomib-based regimen at 1L, whereas lenalidomide-based regimens were most common at 2L. Among patients who received a lenalidomide-sparing regimen at 2L, this was most often a proteasome inhibitor-based regimen. Mortality rate was 26.1/100 person-years, and median (95% confidence interval) survival from 2L initiation was 32.4 (31.2-33.6) months. Survival differed by various factors, shorter survival was reported in the non-ASCT group, those receiving a lenalidomide-sparing regimen at 2L, older patients (≥ 70 years), and those with multiple comorbidities. This analysis provides insight into the real-world use of approved novel MM treatments and highlights an ongoing unmet need to improve outcomes, particularly for selected patient groups.

Objectives: Previous network meta-analysis (NMA) demonstrated advantageous or similar efficacy of baloxavir marboxil (baloxavir) over neuraminidase inhibitors in otherwise healthy (OwH) influenza patients. This analysis assessed the efficacy and safety of baloxavir in the subgroup of high-risk (HR) patients and in the population of uncomplicated influenza consisting of OwH and HR patients with influenza., Methods: A systematic literature review (SLR) was performed in Medline, Embase, CENTRAL and ICHUSHI up to August 8th, 2018. A Bayesian NMA was conducted to compare baloxavir with oseltamivir, zanamivir, laninamivir and peramivir in HR patients and all uncomplicated patients., Results: Based on the SLR, a total of 32 studies were identified as pertinent for the analysis, including 7 studies on HR patients, 13 trials on OwH patients and 14 studies on OwH + HR population. NMA of 10 trials assessing HR patients demonstrated comparable time to alleviation of symptoms for all treatments. Mean decline in virus titer from baseline at 24 h after treatment was significantly greater for baloxavir compared with oseltamivir and peramivir. The risks of total complications and drug-related adverse events were comparable between baloxavir and zanamivir, oseltamivir and laninamivir. These findings were highly consistent with results of the NMA using pooled evidence on the uncomplicated population of OwH and HR patients., Conclusions: Baloxavir was significantly more effective than placebo regarding all outcomes except for the risk of pneumonia. Besides, baloxavir was associated with similar clinical efficacy and safety, and superior antiviral activity compared to other antivirals in HR patients, as well as in the entire population of uncomplicated patients with influenza.

Aim: Baloxavir marboxil (baloxavir) is the first cap-dependent endonuclease inhibitor being studied for the treatment of influenza in single oral dosing regimen. This network meta-analysis (NMA) evaluated the efficacy and safety of baloxavir compared to other antivirals for influenza in otherwise healthy patients., Methods: A systematic literature review was performed on 14 November 2016 in Medline, Embase, CENTRAL, and ICHUSHI to identify randomized controlled trials assessing antivirals for influenza. A NMA including 22 trials was performed to compare the efficacy and safety of baloxavir with other antivirals., Results: The time to alleviation of all symptoms was significantly shorter for baloxavir compared to zanamivir (difference in median time 19.96 h; 95% CrI [3.23, 39.07]). The time to cessation of viral shedding was significantly shorter for baloxavir than zanamivir and oseltamivir (47.00 h; 95% CrI [28.18, 73.86] and 56.03 h [33.74, 87.86], respectively). The mean decline in virus titer from baseline to 24 h was significantly greater for baloxavir than for the other drugs. Other differences in efficacy outcomes were not significant. No significant differences were found between baloxavir and the other antivirals for safety, except total drug-related adverse events where baloxavir demonstrated a decrease compared to oseltamivir and laninamivir., Conclusion: The NMA suggests that baloxavir demonstrated better or similar efficacy results compared to other antivirals with a comparable safety profile. Baloxavir led to a significant decrease in viral titer versus zanamivir, oseltamivir and peramivir and decreased viral shedding versus zanamivir and oseltamivir.

Aims: Acetylsalicylic acid (ASA) is widely used for the prevention of atherothrombotic events in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD), but the risk of vascular events remains high. We aimed at identifying randomised controlled trials (RCTs) on antithrombotic treatments in patients with chronic CAD or PAD., Methods: Searches were conducted on MEDLINE, EMBASE, and CENTRAL on March 1 st , 2018. This systematic review (SR) uses a narrative synthesis to summarize the evidence for the efficacy and safety of antiplatelet and anticoagulant therapies in the population of both chronic CAD or PAD patients., Results: Four RCTs from 27 publications were included. Study groups included 15,603 to 27,395 patients. ASA alone was the most extensively studied ( n = 3); other studies included rivaroxaban with or without ASA ( n = 1), vorapaxar alone ( n = 1), and clopidogrel with ( n = 1) or without ASA ( n = 1). Clopidogrel alone and clopidogrel plus ASA compared to ASA presented similar efficacy with comparable safety profile. Rivaroxaban plus ASA significantly reduced the risk of the composite of cardiovascular death, myocardial infarction, and stroke compared to ASA alone, although major bleeding with rivaroxaban plus ASA increased., Conclusion: There is limited and heterogeneous evidence on the prevention of atherothrombotic events in patients with chronic CAD or PAD. Clopidogrel alone and clopidogrel plus ASA did not demonstrate superiority over ASA alone. A combination of rivaroxaban plus ASA may offer significant additional benefit in reducing cardiovascular outcomes, yet it may increase the risk of bleeding, compared to ASA alone., Competing Interests: RB has served as Principal Investigator on studies conducted by Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, and Leo, and he has acted as a consultant and served on speakers' bureaus for Bayer, BMS, Boehringer Ingelheim, Daiichi-Sankyo, and Pfizer. KB is an employee of Bayer Plc; JBB and MH are employees of Bayer AG. KBO, AJ, and VT are employees of Creativ-Ceutical, who received funding from Bayer AG for the study conduction. MT is a consultant to Creativ-Ceutical. OW is a professor of Health Technology Assessment, University of Glasgow and has received payment for consultancy from Bayer. Bayer holds the trademark for acetylsalicylic acid in several countries, developed and markets rivaroxaban, and funded and oversaw the COMPASS trial; however, we are transparent in COIs; the purpose of this article was to review existing data. Study selection and extraction were carried out by Creativ-Ceutical, and Bayer employees had no effect on the results. All steps of the review were documented., (Copyright © 2020 Rupert Bauersachs et al.)

Purpose: To compare visual outcomes and treatment burden between intravitreally administered aflibercept (IVT-AFL) and ranibizumab (RBZ) treat-and-extend (T&E) regimens in patients with wet age-related macular degeneration (wAMD) at 2 years., Methods: A systematic literature review was carried out in Medline, EMBASE, and CENTRAL in October 2018. Matching-adjusted indirect comparison (MAIC) and/or individual patient data meta-regression was used to connect ALTAIR (assessing IVT-AFL T&E) with other studies, adjusting for between-trial differences in baseline visual acuity and age or baseline visual acuity, age, and polypoidal choroidal vasculopathy (PCV) status. Sensitivity analyses were conducted to test the robustness of the results, including direct MAIC between IVT-AFL T&E (ALTAIR) and RBZ T&E (CANTREAT and TREX-AMD trials)., Results: Six randomized controlled trials (RCTs) (ALTAIR, VIEW 1 and 2, CATT, CANTREAT, and TREX) were included in the analysis. IVT-AFL T&E was assessed in one study, ALTAIR (n = 255), while RBZ T&E was assessed in two trials (n = 327). At 2 years, the median difference (95% credibility interval) between IVT-AFL T&E and RBZ T&E regarding the numbers of Early Treatment Diabetic Retinopathy Study (ETDRS) letters gained was not significant (M1: - 2.29 [- 8.10, 3.58]; M2: - 0.55 [- 6.34, 5.29]). IVT-AFL T&E was associated with significantly fewer injections than RBZ-T&E (M1: - 6.12 [- 7.60, - 4.65]; M2: - 5.93 [- 7.42, - 4.45]). Results of the sensitivity analyses were consistent with the main scenarios., Conclusion: Patients with wAMD receiving an IVT-AFL T&E regimen achieved and maintained improvement in visual acuity with fewer injections over 2 years compared with RBZ T&E. IVT-AFL T&E may therefore serve as the optimal therapy for wAMD, as it was associated with clinical efficacy and minimized treatment burden.

We conducted a systematic review of the literature and network meta-analysis (NMA) to compare the relative effectiveness of antibiotic treatments for Clostridioides (Clostridium) difficile infection (CDI) including vancomycin (VCM), metronidazole (MTZ) and fidaxomicin (FDX). Eligible studies were randomised controlled trials (RCTs) including adults with any severity of CDI that was treated with VCM, MTZ or FDX. The NMA was performed using a Bayesian framework, using a fixed-effects model. The searches identified seven publications for inclusion, which provided five RCTs for VCM versus MTZ, and three RCTs for FDX versus VCM. The NMA showed that for clinical cure rate, there was no difference for FDX versus VCM, and there was a significant difference in favour of FDX versus MTZ (odds ratio [OR]: 1.77; 95% credible interval [CrI] 1.11, 2.83]). For recurrence rate, there was a significant difference in favour of FDX versus both VCM (OR: 0.50; 95% CrI: 0.37, 0.68) and MTZ (OR: 0.44; 95% CrI: 0.27, 0.72). For sustained cure (clinical cure without recurrence), there was a significant difference in favour of FDX versus VCM (OR: 1.61; 95% CrI: 1.27, 2.05) and MTZ (OR: 2.39; 95% CrI: 1.65, 3.47). These findings suggest that FDX and VCM are effective first-line treatments for mild or moderate CDI, whereas MTZ is not, and FDX may be more effective at preventing CDI recurrence than VCM., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: Investigate globally, current treatment patterns, benefit-risk assessments, humanistic, societal and economic burden of platelet transfusion (PT). Methods: Publications from 1998 to June 27, 2018 were identified, based on databases searches including MEDLINE®; Embase and Cochrane Database of Systematic Reviews. Data from studies meeting pre-specified criteria were extracted and validated by independent reviewers. Data were obtained for efficacy and safety from randomized controlled trials (RCTs); data for epidemiology, treatment patterns, effectiveness, safety, humanistic and societal burden from real-world evidence (RWE) studies; and economic data from both. Results: A total of 3425 abstracts, 194 publications (190 studies) were included. PT use varied widely, from 0%-100% of TCP patients; 1.7%-24.5% in large studies (>1000 patients). Most were used prophylactically rather than therapeutically. 5 of 43 RCTs compared prophylactic PT with no intervention, with mixed results. In RWE studies PT generally increased platelet count (PC). This increase varied by patient characteristics and hence did not always translate into a clinically significant reduction in bleeding risk. Safety concerns included infection risk, alloimmunization and refractoriness with associated cost burden. Discussion: In RCTs and RWE studies there was significant heterogeneity in study design and outcome measures. In RWE studies, patients receiving PT may have been at higher risk than those not receiving PT creating potential bias. There were limited data on humanistic and societal burden. Conclusion: Although PTs are used widely for increasing PC in TCP, it is important to understand the limitations of PTs, and to explore the use of alternative treatment options where available.

Objective: The aim of this study was to investigate the impact of methodological choices in a meta-analysis of real-world evidence (RWE) comparing three non-vitamin-K antagonist oral anticoagulants with vitamin K antagonists (VKAs) for the treatment of patients with non-valvular atrial fibrillation (NVAF). Methods: The meta-analysis was based on a systematic review of RWE studies enrolling incident and prevalent patients aged ≥18 years with NVAF and receiving either rivaroxaban, dabigatran, apixaban or a VKA. Five different scenarios were considered to explore the impact of the initial meta-analysis assumptions: (1) using studies that involved only incident patients; (2) excluding studies that only reported crude values and did not consider any adjustment; (3) including all studies independently of possible database overlap; (4) using studies with data on different dosages for rivaroxaban and dabigatran; and (5) assigning quality weights to studies to assess quality of reporting. These scenarios were run on three outcomes: ischemic stroke (IS), myocardial infarction (MI) and intracranial hemorrhage (ICH). Results: Across all scenarios, rivaroxaban was associated with significantly lower risks of IS and ICH than VKAs. In most scenarios, dabigatran was associated with significantly lower risks of IS and ICH. In all scenarios, apixaban was associated with a significantly lower risk of ICH. Conclusions: Sensitivity analyses showed the impact of similar assumptions was different depending on the outcome and the drug considered. The development of recommendations and guidelines for the inclusion of RWE in meta-analyses could prove useful in evaluating the effectiveness of health care interventions.

Objective: Baloxavir marboxil (baloxavir) is the first cap-dependent endonuclease inhibitor being studied for the treatment of influenza in single oral dosing regimen. This network meta-analysis (NMA) evaluated the efficacy and safety of baloxavir compared to other antivirals for influenza in otherwise healthy patients. Methods: A systematic literature review was performed on 14 November 2016 in Medline, Embase, CENTRAL, and ICHUSHI to identify randomized controlled trials assessing antivirals for influenza. A NMA including 22 trials was performed to compare the efficacy and safety of baloxavir with other antivirals. Results: The time to alleviation of all symptoms was significantly shorter for baloxavir compared to zanamivir (difference in median time 19.96 h; 95% CrI [3.23, 39.07]). The time to cessation of viral shedding was significantly shorter for baloxavir than zanamivir and oseltamivir (47.00 h; 95% CrI [28.18, 73.86] and 56.03 h [33.74, 87.86], respectively). The mean decline in virus titer from baseline to 24 h was significantly greater for baloxavir than for the other drugs. Other differences in efficacy outcomes were not significant. No significant differences were found between baloxavir and the other antivirals for safety, except total drug-related adverse events where baloxavir demonstrated a decrease compared to oseltamivir and laninamivir. Conclusions: The NMA suggests that baloxavir demonstrated better or similar efficacy results compared to other antivirals with a comparable safety profile. Baloxavir led to a significant decrease in viral titer versus zanamivir, oseltamivir and peramivir and decreased viral shedding versus zanamivir and oseltamivir.

Aims: Non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) are used to prevent stroke in patients with atrial fibrillation (AF). This paper aimed to evaluate the clinical efficacy and safety of NOACs when compared to VKAs by calculating the number needed to treat (NNT) at 2 years using incidence rates and hazard ratios (HRs) derived from a meta-analysis of studies conducted in real-world settings. Materials and methods: HRs were sourced from a published systematic literature review and a meta-analysis of real-world evidence on the use of NOACs vs VKAs. Rivaroxaban, dabigatran, and apixaban vs VKAs were investigated. The efficacy outcomes included: a composite of ischaemic stroke and systemic embolism (IS/SE), ischaemic stroke (IS), and all-cause mortality. The safety analysis assessed major bleeding and intracranial haemorrhage (ICH). Results: Superiority of NOACs vs VKAs was observed in 10/15 comparisons. Treating patients with rivaroxaban and dabigatran was associated with a reduced risk of IS and all-cause mortality compared to VKAs, with one death prevented every 22 and 32 patients, respectively, and one IS prevented every 206 and 166 patients, respectively. Rivaroxaban was significantly associated with a reduced risk of IS/SE compared to VKA (NNT: 107). No significant differences were observed between apixaban and VKAs. Dabigatran and apixaban were associated with a reduced risk of major bleeding compared to VKA (NNT: 59 and 38, respectively). No significant difference was observed between rivaroxaban and VKAs regarding major bleeding. Rivaroxaban, dabigatran, and apixaban were significantly associated with a reduced risk of ICH (NNT: 205, 115, and 108, respectively). Limitations: Heterogeneity in definitions of major bleeding across studies. Conclusions: The NNT calculation, when approached and interpreted properly, is a practical measure of the effectiveness of a treatment. The calculation based on HRs showed that NOACs are safe and effective alternatives to VKAs in real life.

Objective : Doctor-shopping has significant consequences for patients and payers and can indicate misuse of drugs, polypharmacy, less continuity of care, and increased medical expenses. This study reviewed the literature describing doctor-shoppers in the adult population. Methods : A systematic literature review was performed in PubMed and supplemented by a Google search of grey literature. Overall, 2885 records were identified; 43 papers served as a source of definition of a doctor-shopper, disease, treatment, patient characteristics, patient special needs, country. Results : Definitions of doctor-shopping were heterogeneous. Overall, 40% of studies examined the use of opioids, antidepressants, or psychoactive drugs, while the others focused on chronic or frequent diseases. Most studies were conducted in countries with easy access to healthcare resources (USA, France, Taiwan, Hong Kong). The prevalence of doctor-shopping ranged from 0.5% among opioid users in the USA to 25% of patients registered at general practices in Japan. Comorbidities, active substance abuse, greater distance from healthcare facility, younger age, longer disease and poor patient satisfaction increased doctor-shopping. Conclusions : Knowing the characteristics of doctor-shoppers may help identify such patients and reduce the associated waste of medical resources, but concerns about the misuse of drugs or healthcare resources should not prevent proper disease management.