Comparative Effectiveness of Bimekizumab and Risankizumab in Patients with Psoriatic Arthritis at 52 Weeks Assessed Using a Matching-Adjusted Indirect Comparison.

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.

Matching-Adjusted Indirect Comparison of the 52-Week Efficacy of Bimekizumab Versus Secukinumab and Ixekizumab for the Treatment of Radiographic Axial Spondyloarthritis.

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.

Cost-effectiveness of romosozumab for the treatment of postmenopausal women with osteoporosis at high risk of fracture in Belgium.

This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium. PURPOSE: This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021. METHODS: A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed. RESULTS: Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis. CONCLUSION: Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.

Comparative Effectiveness of Bimekizumab and Secukinumab in Patients with Psoriatic Arthritis at 52 Weeks Using a Matching-Adjusted Indirect Comparison.

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.

Comparative Effectiveness of Bimekizumab and Guselkumab in Patients with Psoriatic Arthritis at 52 Weeks Assessed Using a Matching-Adjusted Indirect Comparison.

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.

Improvement in work productivity among psoriatic arthritis patients treated with biologic or targeted synthetic drugs: a systematic literature review and meta-analysis.

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.

Psoriatic arthritis (PsA) has a major impact on patients' lives, including their ability to work by causing absence and reducing productivity. By pooling together published studies (12 studies, corresponding to 3741 patients) and comparing what patients reported before starting treatment to during treatment, we found that over the course of treatment with biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs), patients with PsA had an average of 18% higher total work productivity, translating to a 41% reduced impact of PsA at the group level (without looking at comparisons to a placebo response). It is important for health professionals and patients to know that work outcomes affected by PsA are improved when patients take b/tsDMARDS.

Comparative efficacy and safety of bimekizumab in psoriatic arthritis: a systematic literature review and network meta-analysis.

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.

Cost-effectiveness analysis of bimekizumab for the treatment of active psoriatic arthritis in Sweden.

AIMS: To evaluate the cost-effectiveness of bimekizumab, an inhibitor of IL-17F and IL-17A, against biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARD) for psoriatic arthritis (PsA) from the Swedish healthcare system perspective. MATERIALS AND METHODS: A Markov model was developed to simulate the clinical pathway of biologic [b] DMARD-naïve or tumor necrosis factor inhibitor experienced [TNFi-exp] PsA patients over a lifetime horizon. Treatment response was incorporated as achievement of the American College of Rheumatology 50% (ACR50) and Psoriasis Area and Severity Index 75% (PASI75) response, and changes in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score. The efficacy of bimekizumab was obtained from the BE OPTIMAL (bDMARD-naïve) and BE COMPLETE (TNFi-experienced) trials while a network meta-analysis (NMA) informed the efficacy of the comparators. Resource use and drug costs were obtained from published studies and databases of drug retail prices in Sweden. A willingness-to-pay threshold of €50,000 per quality-adjusted life year (QALY) was applied. RESULTS: In bDMARD-naïve patients, bimekizumab achieved greater QALYs (14.08) than with all comparators except infliximab (14.22), dominated guselkumab every 4 and 8 weeks, ixekizumab, secukinumab 300 mg, ustekinumab 45 mg and 90 mg, and was cost-effective against risankizumab, tofacitinib, upadacitinib and TNFis, except adalimumab biosimilar. In TNFi-experienced patients, bimekizumab led to greater QALYs (13.56) than all comparators except certolizumab pegol (13.84), and dominated ixekizumab and secukinumab 300 mg while being cost-effective against all other IL-17A-, IL-23- and JAK inhibitors. LIMITATIONS: An NMA informed the comparative effectiveness estimates. Given gaps in evidence of disease management and indirect costs specific to HAQ-DI scores, and sequential clinical trial evidence in PsA, non-PsA cost data from similar joint conditions were used, and one line of active treatment followed by best supportive care was assumed. CONCLUSIONS: Bimekizumab was cost-effective against most available treatments for PsA in Sweden, irrespective of prior TNFi exposure.

Achievement of more stringent disease control is associated with reduced burden on workplace and household productivity: results from long-term certolizumab pegol treatment in patients with psoriatic arthritis.

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,