Matching-adjusted Indirect Comparison Research Articles

Comparative efficacy and safety of osilodrostat vs metyrapone for the treatment of Cushing's syndrome - a matching-adjusted indirect comparison using LINC-3 and LINC-4

Comparative efficacy and safety of osilodrostat vs metyrapone for the treatment of Cushing's syndrome - a matching-adjusted indirect comparison using LINC-3 and LINC-4

Long-Term Comparative Efficacy and Safety of Risdiplam and Nusinersen in Children with Type1 Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disease characterized by a loss of motor neurons and progressive muscle weakness. Children with untreated type1 SMA never sit independently and require increasing levels of ventilatory support as the disease progresses. Without intervention, and lacking ventilatory support, death typically occurs before the age of 2years. There are currently no head-to-head trials comparing available treatments in SMA. Indirect treatment comparisons are therefore needed to provide information on the relative efficacy and safety of SMA treatments for healthcare decision-making. The long-term efficacy and safety of risdiplam versus nusinersen in children with type1 SMA was evaluated using indirect treatment comparison methodology to adjust for differences between population baseline characteristics, to reduce any potential bias in the comparative analysis. An unanchored matching-adjusted indirect comparison was conducted using risdiplam data from 58 children in FIREFISH (NCT02913482) and published aggregate nusinersen data from 81 children obtained from the ENDEAR (NCT02193074) and SHINE (NCT02594124) clinical trials with at least 36months of follow-up. Children with type1 SMA treated with risdiplam had a 78% reduction in the rate of death, an 81% reduction in the rate of death or permanent ventilation, and a 57% reduction in the rate of serious adverse events compared with children treated with nusinersen. Children treated with risdiplam also had a 45% higher rate of achieving a Hammersmith Infant Neurological Examination, Module2 motor milestone response and a 186% higher rate of achieving a ≥ 4-point improvement in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders compared with children treated with nusinersen. Long-term data supported risdiplam as a superior alternative to nusinersen in children with type1 SMA. Video abstract available for this article. Video abstract (MP4 184542 KB).

Comparing survival in trial- versus routine-care advanced urothelial cancer patients on immune checkpoint blockade.

Although recent trials involving first-line immune checkpoint inhibitors have expanded treatment options for patients with advanced urothelial carcinoma (aUC) who are ineligible for standard cisplatin-based chemotherapy, there exists limited evidence for whether trial efficacy translates into real-world effectiveness for patients seen in routine care. This retrospective cohort study compares differences in overall survival (OS) between KEYNOTE-052 trial participants and routine-care patients receiving first-line pembrolizumab monotherapy. A routine-care patient cohort was constructed from the Flatiron Health database using trial eligibility criteria and was weighted to balance EHR and trial patient characteristics using matching-adjusted indirect comparisons. The routine-care cohort was older, more likely to be female, and more often cisplatin-ineligible due to renal dysfunction. ECOG performance status was comparable between the cohorts. Median OS was 9 months (95% CI 7-16) in the weighted routine-care cohort and 11.3 months (9.7-13.1) in the trial cohort. No significant differences between the Kaplan-Meier OS curves were detected (p = 0.76). Survival probabilities were similar between the weighted routine-care and trial cohorts at 12-, 24-, and 36- months (0.45 vs. 0.47, 0.31 vs. 0.31, 0.26 vs. 0.23, respectively). Notably, routine care patients had modestly lower survival at 3 months compared to trial participants (0.69 vs. 0.83, respectively). Our results provide reassurance that cisplatin-ineligible aUC patients receiving first-line immunotherapy in routine care experience similar benefits to those observed in trial patients.

Efgartigimod and Ravulizumab for Treating Acetylcholine Receptor Auto-antibody-Positive (AChR-Ab+) Generalized Myasthenia Gravis: Indirect Treatment Comparison.

Efgartigimod and ravulizumab, both approved for treating acetylcholine receptor auto-antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG), have not been directly compared. This paper assessed comparative effects of efgartigimod vs. ravulizumab for treating adults with AChR-Ab+gMG using indirect treatment comparison methods. The matching-adjusted indirect comparison used data from two randomized trials of adult men and women. The ADAPT (efgartigimod vs. placebo; individual patient data available) population was reweighted to match the CHAMPION (ravulizumab vs. placebo; index study; aggregate data available) population. The relative effect of efgartigimod versus placebo was estimated in this reweighted population and compared with the observed ravulizumab versus placebo effect to estimate the efgartigimod versus ravulizumab effect. The outcomes were Myasthenia Gravis Activities of Daily Living (MG-ADL), QuantitativeMyasthenia Gravis (QMG), and Myasthenia Gravis Quality of Life 15-item-revised scale (MG-QoL15r) assessed as cumulative effect (area under the curve; AUC) over 26 weeks (primary) and change from baseline at 4 weeks and time of best response (week 4 for efgartigimod; week 26 for ravulizumab). For MG-QoL15r, efgartigimod had a statistically significant improvement compared with ravulizumab over 26 weeks [mean difference (95% confidence interval): -52.6 (-103.0, -2.3)], at week 4 [-4.0 (-6.6, -1.4)], and at time of best response [-3.9 (-6.5, -1.3)]. Efgartigimod had a statistically significant improvement over ravulizumab in MG-ADL at week 4 [-1.9 (-3.3, -0.5)] and at time of best response [-1.4 (-2.8, 0.0)] and in QMG at week 4 [-3.2 (-5.2, -1.2)] and at time of best response [-3.0 (-5.0, -1.0)]. For AUC over 26 weeks, improvements were not significantly different between efgartigimod and ravulizumab for MG-ADL [-8.7 (-36.1, 18.8)] and QMG [-13.7 (-50.3, 22.9)]. Efgartigimod may provide a faster and greater improvement over 26 weeks in quality of life than ravulizumab in adults with AChR-Ab+gMG. Efgartigimod showed faster improvements in MG-ADL and QMG than ravulizumab.

Comparative analysis of the efficacy of seniprutug (BCD-180) and adalimumab in the treatment of active radiographic axial spondyloarthritis: results of a systematic review and matching-adjusted indirect comparison

Objective: to compare the clinical efficacy of seniprutug (BCD-180) and adalimumab (ADA) in the treatment of adults with active radiographic axial spondyloarthritis (r-axSpA).Materials and methods. Based on the results of a previously conducted systematic review, an unanchored matching-adjusted indirect comparison (MAIC) was performed, adjusting for confounding factors. The analysis was based on the results of randomized placebo-controlled clinical trials of seniprutug (BCD-180-2/ELEFTA, NCT05445076) and ADA (ATLAS, NCT00085644) that met the selection criteria. We chose ASAS40 and ASAS20 measurements at week 24 as efficacy outcomes. Initial BASDAI and BASFI indices, proportion of women in the study population, time from disease onset, and baseline C-reactive protein (CRP) levels were considered as confounders.Results and discussion. The MAIC showed a statistically significant advantage in the clinical efficacy of seniprutug (BCD-180) over ADA. When adjusted, the odds ratios (OR) with 95% confidence intervals (CI) for seniprutug (BCD-180)/ADA were 1.86 (1.15; 3.02) and 2.21 (1.34; 3.72) for ASAS40 and ASAS20, respectively, at week 24.Conclusion. The MAIC demonstrated statistically significant superiority of seniprutug (BCD-180) over ADA on the key efficacy endpoints ASAS40 and ASAS20 at week 24 in adults with active r-axSpA. The inclusion of the innovative domestic drug seniprutug into treatment paradigm of active r-axSpA will potentially reduce the socio-economic burden of this disease by providing an affordable, effective and safe therapy while optimizing healthcare costs

Methods for Indirect Treatment Comparison: Results from a Systematic Literature Review.

Health technology assessment (HTA) agencies express a clear preference for randomized controlled trials when assessing the comparative efficacy of two or more treatments. However, an indirect treatment comparison (ITC) is often necessary where a direct comparison is unavailable or, in some cases, not possible. Numerous ITC techniques are described in the literature. A systematic literature review (SLR) was conducted to identify all the relevant literature on existing ITC techniques, provide a comprehensive description of each technique and evaluate their strengths and limitations from an HTA perspective in order to develop guidance on the most appropriate method to use in different scenarios. Electronic database searches of Embase and PubMed, as well as grey literature searches, were conducted on 15 November 2021. Eligible articles were peer-reviewed papers that specifically described the methods used for different ITC techniques and were written in English. The review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 73 articles were included in the SLR, reporting on seven different ITC techniques. All reported techniques were forms of adjusted ITC. Network meta-analysis (NMA) was the most frequently described technique (in 79.5% of the included articles), followed by matching-adjusted indirect comparison (MAIC) (30.1%), network meta-regression (24.7%), the Bucher method (23.3%), simulated treatment comparison (STC) (21.9%), propensity score matching (4.1%) and inverse probability of treatment weighting (4.1%). The appropriate choice of ITC technique is critical and should be based on the feasibility of a connected network, the evidence of heterogeneity between and within studies, the overall number of relevant studies and the availability of individual patient-level data (IPD). MAIC and STC were found to be common techniques in the case of single-arm studies, which are increasingly being conducted in oncology and rare diseases, whilst the Bucher method and NMA provide suitable options where no IPD is available. ITCs can provide alternative evidence where direct comparative evidence may be missing. ITCs are currently considered by HTA agencies on a case-by-case basis; however, their acceptability remains low. Clearer international consensus and guidance on the methods to use for different ITC techniques is needed to improve the quality of ITCs submitted to HTA agencies. ITC techniques continue to evolve quickly, and more efficient techniques may become available in the future.

The cost-effectiveness of iruplinalkib versus alectinib in anaplastic lymphoma kinase-positive crizotinib-resistant advanced non-small-cell lung cancer patients in China.

Iruplinalkib is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) with efficacy in patients with ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC), which is independently developed by a Chinese pharmaceutical company. This study examined the cost-effectiveness of iruplinalkib versus alectinib in the Chinese healthcare setting. A partitioned survival model was developed to project the economic and health outcomes. Efficacy was derived using unanchored matching-adjusted indirect comparison (MAIC). Cost and utility values were obtained from the literature and experts' opinions. Deterministic and probabilistic sensitivity analyses (PSA) were carried out to evaluate the model's robustness. Treatment with iruplinalkib versus alectinib resulted in a gain of 0.843 quality-adjusted life years (QALYs) with incremental costs of $20,493.27, resulting in an incremental cost-effectiveness ratio (ICER) of $24,313.95/QALY. Parameters related to relative efficacy and drug costs were the main drivers of the model outcomes. From the PSA, iruplinalkib had a 90% probability of being cost-effective at a willingness-to-pay threshold of $37,863.56/QALY. Compared to alectinib, iruplinalkib is a cost-effective therapy for patients with ALK-positive crizotinib-resistant advanced NSCLC.

Matching-Adjusted Indirect Comparison of the Efficacy at Week32 of Tralokinumab and Dupilumab in the Treatment of Moderate-to-Severe Atopic Dermatitis.

Tralokinumab and dupilumab are biological agents licensed for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients who are candidates for systemic treatment. However, no head-to-head studies of their efficacy have been conducted. This study indirectly compared the efficacy of tralokinumab and dupilumab, both in combination with topical corticosteroids (TCS), at week32. An unanchored matching-adjusted indirect comparison was conducted using individual patient data (IPD) from the ECZTRA3 tralokinumab trial and aggregate data from the LIBERTY AD CHRONOS dupilumab trial. IPD were selected by applying inclusion criteria from LIBERTY AD CHRONOS and weighting to match summary baseline characteristics-age, sex, race, body mass index, disease duration, Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Dermatology Life Quality Index (DLQI) and SCORing Atopic Dermatitis index-of patients treated with dupilumab. Week32 outcomes of interest were 50%, 75% or 90% improvements in EASI (EASI-50, EASI-75 and EASI-90), IGA scores of 0 or 1 (IGA0/1), ≥ 4-point improvement in worst daily pruritus numerical rating scale (NRS) score, and mean improvements in DLQI and the Patient Oriented Eczema Measure (POEM). After matching, tralokinumab and dupilumab, both in combination with TCS, showed similar efficacy across clinical response endpoints at week32 (IGA0/1, tralokinumab 49.9% vs dupilumab 39.3%; EASI-50, 78.9% vs 77.5%; EASI-75, 71.5% vs 71.9%; EASI-90, 53.3% vs 56.2%). The mean change from baseline in DLQI was statistically significantly larger in the matched tralokinumab plus TCS population than in the dupilumab plus TCS arm (- 12.1 vs - 10.4, p = 0.005). Changes in POEM and worst daily pruritus NRS were similar in the two groups. The results of this analysis demonstrate that, in combination with TCS, tralokinumab and dupilumab have similar efficacy in the treatment of moderate-to-severe AD at 32weeks of therapy.

An indirect comparison of acalabrutinib with and without obinutuzumab vs zanubrutinib in treatment-naive CLL

AbstractThe efficacy and safety of acalabrutinib plus obinutuzumab and acalabrutinib monotherapy vs zanubrutinib in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma without del(17p) were compared using an unanchored matching-adjusted indirect comparison. Individual patient-level data from ELEVATE-TN (acalabrutinib plus obinutuzumab, n = 162; acalabrutinib monotherapy, n = 163) were weighted to match published aggregate baseline data from SEQUOIA cohort 1, which excluded patients with del(17p) (zanubrutinib, n = 241), using variables that were prognostic/predictive of investigator-assessed progression-free survival (INV-PFS) in an exploratory Cox regression analysis of ELEVATE-TN. After matching, INV-PFS was longer with acalabrutinib plus obinutuzumab (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.23-0.74) and comparable with acalabrutinib monotherapy (HR, 0.91; 95% CI, 0.53-1.56) vs zanubrutinib. Acalabrutinib monotherapy had significantly lower odds of any grade hypertension vs zanubrutinib (odds ratio [OR], 0.44; 95% CI, 0.20-0.99), whereas acalabrutinib plus obinutuzumab had significantly higher odds of neutropenia (OR, 2.19; 95% CI, 1.33-3.60) and arthralgia (OR, 2.33; 95% CI, 1.37-3.96) vs zanubrutinib. No other significant differences in safety were observed. In summary, acalabrutinib plus obinutuzumab had longer INV-PFS with increased odds of neutropenia and arthralgia than zanubrutinib, whereas acalabrutinib monotherapy had similar INV-PFS with lower odds of any grade hypertension. These trials were registered at www.ClinicalTrials.gov as #NCT02475681 and #NCT03734016.

Cost-effectiveness analysis 3L of axicabtagene ciloleucel vs tisagenlecleucel and lisocabtagene maraleucel in Japan.

Aim: Cost-effectiveness analysis (CEA) was performed to compare axicabtagene ciloleucel (axi-cel) with tisagenlecleucel (tisa-cel) and lisocabtagene (liso-cel) for treatment of relapsed or refractory large B-cell lymphoma in adult patients after ≥2 lines of therapy in Japan. Materials & methods: Cost-effectiveness analysis was conducted using the partition survival mixture cure model based on the ZUMA-1 trial and adjusted to the JULIET and TRANSCEND trials using matching-adjusted indirect comparisons. Results & conclusion: Axi-cel was associated with greater incremental life years (3.13 and 2.85) and incremental quality-adjusted life-years (2.65 and 2.24), thus generated lower incremental direct medical costs (-$976.29 [-¥137,657] and -$242.00 [-¥34,122]), compared with tisa-cel and liso-cel. Axi-cel was cost-effective option compared with tisa-cel and liso-cel from a Japanese payer's perspective.

Matching-adjusted Indirect Comparison of Troriluzole Versus Untreated Natural History Cohort in Spinocerebellar Ataxia (S35.009)

Matching-adjusted Indirect Comparison of Troriluzole Versus Untreated Natural History Cohort in Spinocerebellar Ataxia (S35.009)

Matching-adjusted Indirect Comparison of Current Treatments for NMOSD and Evaluation of Long-term Effectiveness (P10-14.006)

Matching-adjusted Indirect Comparison of Current Treatments for NMOSD and Evaluation of Long-term Effectiveness (P10-14.006)

Advancing unanchored simulated treatment comparisons: A novel implementation and simulation study.

Population-adjusted indirect comparisons, developed in the 2010s, enable comparisons between two treatments in different studies by balancing patient characteristics in the case where individual patient-level data (IPD) are available for only one study. Health technology assessment (HTA) bodies increasingly rely on these methods to inform funding decisions, typically using unanchored indirect comparisons (i.e., without a common comparator), due to the need to evaluate comparative efficacy and safety for single-arm trials. Unanchored matching-adjusted indirect comparison (MAIC) and unanchored simulated treatment comparison (STC) are currently the only two approaches available for population-adjusted indirect comparisons based on single-arm trials. However, there is a notable underutilisation of unanchored STC in HTA, largely due to a lack of understanding of its implementation. We therefore develop a novel way to implement unanchored STC by incorporating standardisation/marginalisation and the NORmal To Anything (NORTA) algorithm for sampling covariates. This methodology aims to derive a suitable marginal treatment effect without aggregation bias for HTA evaluations. We use a non-parametric bootstrap and propose separately calculating the standard error for the IPD study and the comparator study to ensure the appropriate quantification of the uncertainty associated with the estimated treatment effect. The performance of our proposed unanchored STC approach is evaluated through a comprehensive simulation study focused on binary outcomes. Our findings demonstrate that the proposed approach is asymptotically unbiased. We argue that unanchored STC should be considered when conducting unanchored indirect comparisons with single-arm studies, presenting a robust approach for HTA decision-making.

Efficacy and Safety of PEGylated Interferons for Relapsing-Remitting Multiple Sclerosis in Adult Patients: Results of Matching-Adjusted Indirect Comparison

Introduction. Beta interferons are effective and safe agents for the treatment of relapsing-remitting multiple sclerosis (RRMS). PEGylated interferons have been developed in order to increase patient adherence. Direct comparisons of the efficacy and safety of PEGylated interferons have not yet been conducted.
 Our objective was to evaluate the efficacy and safety of SamPEG-IFN-β1a versus PEG-IFN-β1a in adult patients with RRMS.
 Materials and methods. We conducted a systematic search of randomized clinical trials (RCTs) using the PubMed, Embase and eLIBRARY.RU databases. Efficacy was assessed based on the proportion of patients with disease relapses and the annualized relapse rate (ARR) during the 1st and the 2nd years of treatment. Safety was assessed by the number of patients with adverse events (AEs), serious AEs (SAEs), and any AEs that led to the treatment discontinuation. We conducted pairwise matching-adjusted indirect comparison (MAIC) to assess comparative efficacy of PEGylated IFNs. To evaluate the efficacy, hypotheses of non-inferiority of SamPEG-IFN-β1a to PEG-IFN-β1a and superiority of SamPEG-IFN-β1a over PEG-IFN-β1a were tested.
 Results. Based on results of the systematic review, four articles were selected wherein the results of phase 3 clinical trial of PEG-IFN-β1a and phase 2–3 clinical trial of SamPEG-IFN-β1a were described. In PEG-IFN-β1a group (n = 512) the agent was administered once every 2 weeks, in SamPEGIFN-β1a group (n = 114) the agent was administered at a dose of 240 μg. The analysis results confirmed the hypothesis of SamPEG-IFN-β1a non-inferiority to PEG-IFN-β1a in efficacy, while SamPEG-IFN-β1a superiority over PEG-IFN-β1a in efficacy was not confirmed. The hypothesis of SamPEG-IFN-β1a superiority over PEG-IFN-β1a in safety was also confirmed based on a significantly lower incidence of SAEs and any AEs that led to treatment discontinuation.
 Conclusions. The proportion of patients with relapses and the ARR in 1 year and in 2 years of therapy indicates that SamPEG-IFN-β1a is non-inferior to PEG-IFN-β1a in efficacy. SamPEG-IFN-B1a demonstrated a more favourable safety profile than PEG-IFN-B1a as showing less odds of SAEs and AEs leading to treatment discontinuation.

Indirect comparisons of relative efficacy estimates of zuranolone and selective serotonin reuptake inhibitors for postpartum depression

Aims: Estimate relative efficacy of zuranolone, a novel oral, Food and Drug Administration-approved treatment for postpartum depression (PPD) in adults vs. selective serotonin reuptake inhibitors (SSRIs) and combination therapies used for PPD in the United States. Materials and methods: Randomized controlled trials (RCTs) for zuranolone and SSRIs, identified from systematic review, were used to construct evidence networks, linking via common comparator arms. Due to heterogeneity in placebo responses, matching-adjusted indirect comparison (MAIC) was applied, statistically weighting the zuranolone treatment arm of Phase 3 SKYLARK Study (NCT04442503) to the placebo arm of RCTs investigating SSRIs for PPD. MAIC outputs were applied in Bucher indirect treatment comparisons (ITCs) and network meta-analysis (NMA), using Edinburgh Postnatal Depression Scale (EPDS) and 17-item Hamilton Rating Scale for Depression (HAMD-17) change from baseline (CFB) on Days 3, 15, 28 (Month 1), 45, and last observation (Day 45, Week 12/18). Results: Larger EPDS CFB was observed among zuranolone-treated vs. SSRI-treated patients from Day 15 onward. Zuranolone-treated (vs. SSRI-treated) patients exhibited 4.22-point larger reduction in EPDS by Day 15 (95% confidence interval: -6.16, -2.28) and 7.43-point larger reduction at Day 45 (-9.84, -5.02) with Bucher ITC. NMA showed EPDS reduction for zuranolone was 4.52 (-6.40, -2.65) points larger than SSRIs by Day 15 and 7.16 (-9.47, -4.85) larger at Day 45. Lack of overlap between study populations substantially reduced effective sample size post-matching, making HAMD-17 CFB analysis infeasible. Limitations: Limited population overlap between SKYLARK Study and RCTs reduced feasibility of undertaking HAMD-17 CFB ITCs and may introduce uncertainty to EPDS CFB ITC results. Conclusions: Analysis showed zuranolone-treated patients with PPD experienced greater symptom improvement than SSRI-treated patients from Day 15 onward, with largest mean difference at Day 45. Adjusting for differences between placebo arms, zuranolone may be associated with greater PPD symptom improvement (measured by EPDS) vs. SSRIs.

Matching-Adjusted Indirect Comparison of Brexucabtagene Autoleucel (ZUMA-2) and Pirtobrutinib (BRUIN) in Patients with Relapsed/Refractory Mantle Cell Lymphoma Previously Treated with a Covalent Bruton Tyrosine KinaseInhibitor.

Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) often require multiple lines of treatment and have a poor prognosis, particularly after failing covalent Bruton tyrosine kinase inhibitor (cBTKi) therapy. Newer treatments such as brexucabtagene autoleucel (brexu-cel, chimeric antigen receptor Tcell therapy) and pirtobrutinib (non-covalent BTKi) show promise in improving outcomes. Without direct comparative evidence, an unanchored matching-adjusted indirect comparison was conducted to estimate the relative treatment effects of brexu-cel and pirtobrutinib for post-cBTKi R/R MCL. Using logistic propensity score models, individual patient-level data from ZUMA-2 brexu-cel-infused population (N = 68) were weighted to match pre-specified clinically relevant prognostic factors based on study-level data from the BRUIN cBTKi pre-treated cohort (N = 90). The base-case model incorporated the five most pertinent factors reported in ≥ 50% of both trial populations: morphology, MCL International Prognostic Index, number of prior lines of therapy, disease stage, and prior autologous stem cell transplant. A sensitivity analysis additionally incorporated TP53 mutation and Ki-67 proliferation. Relative treatment effects were expressed as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). In the base-case model, brexu-cel was associated with higher rates of objective response (OR 10.39 [95%CI 2.81-38.46]) and complete response (OR 10.11 [95%CI 4.26-24.00]), and improved progression-free survival (HR0.44 [95%CI 0.25-0.75]), compared to pirtobrutinib. Overall survival and duration of response favored brexu-cel over pirtobrutinib but the differences crossed the bounds for statistical significance. Findings were consistent across the adjusted and unadjusted analyses. Findings suggest that brexu-cel may offer clinically and statistically significant benefits regarding objective response, complete response, and progression-free survival compared to pirtobrutinib among patients with R/R MCL after prior cBTKi therapy. Given the short follow-up and high degree of censoring in BRUIN, an analysis incorporating updated BRUIN data may provide more definitive overall survival results.

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

Matching-adjusted indirect comparisons (MAIC) were used to assess the relative efficacy of bimekizumab 160mg every 4weeks (Q4W) compared to guselkumab 100mg Q4W or every 8weeks (Q8W) at 48/52weeks 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). Relevant trials were identified as part of a systematic literature review. For patients who were bDMARD-naïve, individual patient data (IPD) from BEOPTIMAL (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. 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 week52. 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 week52. In patients who were TNFi-IR, bimekizumab had a greater likelihood in achieving all evaluated outcomes compared to guselkumab Q8W at week48/52 (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). 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 week48/52. Bimekizumab had a more favorable likelihood than guselkumab in achieving more stringent treatment outcomes. NCT03895203, NCT03896581, NCT04009499, NCT03158285, NCT03796858.

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

Matching-adjusted indirect comparisons (MAICs) were used to compare the efficacy of bimekizumab and secukinumab 150mg and 300mg at 52weeks 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). 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 FUTURE2 using secukinumab 150mg and 300mg 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. In patients who were bDMARD-naïve, bimekizumab had a greater likelihood of ACR70 response than secukinumab 150mg (odds ratio [95% confidence interval] 2.39 [1.26, 4.53]; p = 0.008) and secukinumab 300mg (2.03 [1.11, 3.72]; p = 0.021) at 52weeks. In patients who were TNFi-IR, bimekizumab had a greater likelihood of response compared to secukinumab 150mg 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 300mg for ACR50 (2.44 [1.06, 5.65]; p = 0.037) and MDA (2.92 [1.20, 7.09]; p = 0.018) at 52weeks. In this MAIC analysis, the efficacy of bimekizumab, as demonstrated by the likelihood of ACR20/50/70 and MDA response at 52weeks, was greater or comparable to secukinumab 150mg and 300mg for patients with PsA who were bDMARD-naïve and TNFi-IR. NCT03895203, NCT03896581, NCT04009499, NCT01752634, NCT01989468, NCT02294227, NCT02404350.

A matching-adjusted indirect comparison of results from REDUCE and RESPECT—two randomized trials on patent foramen ovale closure devices to prevent recurrent cryptogenic stroke

Aims Two randomized clinical trials, REDUCE and RESPECT, demonstrated that patent foramen ovale (PFO) closure in combination with antithrombotic therapy was more effective for the prevention of recurrent ischemic stroke compared with antithrombotic therapy alone. The aim of this study was to determine the relative efficacy and safety of the PFO closure devices used in REDUCE (HELEX and CARDIOFORM Septal Occluders) compared with the device used in RESPECT (Amplatzer PFO Occluder). Methods An unanchored matching-adjusted indirect comparison (MAIC) of the PFO closure arms of the REDUCE and RESPECT trials was performed using patient-level data from REDUCE weighted to match baseline characteristics from RESPECT. Comparisons of the following outcomes were made between the devices assessed in the trials: risk of recurrent ischemic stroke; recurrent ischemic stroke one year after randomization; any serious adverse event (SAE) related to the procedure or device; and atrial fibrillation or atrial flutter as an SAE related to the procedure or device. Results After conducting the MAIC, baseline characteristics were well-matched between the two trials. Compared to RESPECT, PFO closure using the devices from REDUCE resulted in a hazard ratio of 0.46 (95% confidence interval [CI] 0.15–1.43; p = 0.17) for the risk of recurrent stroke. For the recurrence of stroke after one year, SAE related to the procedure or device, and atrial fibrillation or atrial flutter as SAE related to the procedure or device, the MAIC resulted in a rate difference of −0.68 (95%CI −2.06 to 0.70; p = .34), −1.29 (95%CI −3.82 to 1.25; p = .32), and −0.19 (95%CI −1.16 to 0.78; p = .71), respectively. These findings were consistent across scenario analyses. Conclusions This MAIC analysis found no statistically significant differences in efficacy and safety outcomes between PFO closure with the HELEX and CARDIOFORM Septal Occluders versus the Amplatzer PFO Occluder, as used in the REDUCE and RESPECT trials.

A comprehensive review and shiny application on the matching-adjusted indirect comparison.

Population-adjusted indirect comparison (PAIC) is an increasingly used technique for estimating the comparative effectiveness of different treatments for the health technology assessments when head-to-head trials are unavailable. Three commonly used PAIC methods include matching-adjusted indirect comparison (MAIC), simulated treatment comparison (STC), and multilevel network meta-regression (ML-NMR). MAIC enables researchers to achieve balanced covariate distribution across two independent trials when individual participant data are only available in one trial. In this article, we provide a comprehensive review of the MAIC methods, including their theoretical derivation, implicit assumptions, and connection to calibration estimation in survey sampling. We discuss the nuances between anchored and unanchored MAIC, as well as their required assumptions. Furthermore, we implement various MAIC methods in a user-friendly R Shiny application Shiny-MAIC. To our knowledge, it is the first Shiny application that implements various MAIC methods. The Shiny-MAIC application offers choice between anchored or unanchored MAIC, choice among different types of covariates and outcomes, and two variance estimators including bootstrap and robust standard errors. An example with simulated data is provided to demonstrate the utility of the Shiny-MAIC application, enabling a user-friendly approach conducting MAIC for healthcare decision-making. The Shiny-MAIC is freely available through the link: https://ziren.shinyapps.io/Shiny_MAIC/.