E Palaka

A Matching-Adjusted Indirect Comparison of Sonidegib and Vismodegib in Advanced Basal Cell Carcinoma

Objectives Based on single-arm trial data (BOLT), sonidegib was approved in the US and EU to treat locally advanced basal cell carcinomas (BCCs) ineligible for curative surgery or radiotherapy. Vismodegib, the other approved targeted therapy, also was assessed in a single-arm trial (ERIVANCE). We examined the comparative effectiveness of the two drugs using a matching-adjusted indirect comparison (MAIC) versus an unadjusted indirect comparison. Methods After comparing trials and identifying potential prognostic factors, an MAIC was conducted to adjust for differences in key patient baseline characteristics. Due to BOLTs small sample size, the number of matching variables was restricted to two. Efficacy results for sonidegib were generated so that selected baseline characteristics matched those from ERIVANCE and were compared with published ERIVANCE results. Results Matching variables were baseline percentages of patients receiving prior radiotherapy and surgery. After weighting, sonidegib objective response rate (ORR) and median progression-free survival (PFS) were effectively unchanged (prematched versus postmatched ORR and PFS, 56.1% versus 56.7% and 22.1 versus 22.1 months, resp.). Vismodegibs ORR and PFS were 47.6% and 9.5 months. Conclusions Comparative effectiveness of sonidegib versus vismodegib remains unchanged after adjusting BOLT patient-level data to match published ERIVANCE baseline percentages of patients receiving prior surgery and radiotherapy.

THU0437 Secukinumab for The Treatment of Psoriatic Arthritis: Comparative Effectiveness Results versus Licensed Biologics and Apremilast from A Network Meta-Analysis

Background Secukinumab (SEC) is approved for the treatment of active PsA in adults who have responded inadequately to DMARD therapy. The FUTURE 1 and 2 RCTs which included biologic-naïve and biologic-experienced patients, demonstrated superiority of SEC 150 mg and 300 mg over placebo. As no direct trial comparisons are yet available there is a need for comparative effectiveness assessment. Objectives Comparative assessment of SEC via network meta-analysis (NMA) vs. licensed biologics and apremilast in adults with active PsA who had failed conventional DMARD therapy. Methods A systematic review of the literature (November 2015) identified 20 relevant RCTs. NMAs were conducted following health technology assessment guidance using Bayesian fixed-effects models. PASI and ACR responses and their credible intervals (CrIs), which can be interpreted similarly to CIs, were modelled using a conditional binomial likelihood NMA with probit link function. The results of pairwise comparisons are presented for SEC using relative risks (RRs) [95%CrI]. Non-responder imputation data were used for all comparators except golimumab QM (GOL) and infliximab 5 mg/kg Q2M (INF) for which only last observation carried forward data were available. Analyses were performed in biologic-naïve, biologic-experienced, and mixed populations at week 16 for ACR and at weeks 12–16 for PASI. Results At week 16 in the biologic-naïve population, ACR20 responses were statistically significantly higher for SEC 150 mg (61%) and 300 mg (58%) than for ustekinumab QM (UST) 45 mg (RR 1.95 [1.29–2.86] and RR 1.84 [1.21–2.74], respectively), and for SEC 150 mg vs UST 90 mg (RR 1.52 [1.03–2.16]). ACR20 responses were statistically significantly higher for SEC 150 and 300 mg vs. apremilast BID (APR) 20 mg (RR 2.51 [1.52–4.29] and RR 2.37 [1.39–4.12] respectively), and for SEC 150 mg vs. APR 30 mg (RR 1.72 [1.09–2.71]). Comparisons between SEC and anti-TNFs did not show statisticall significance. For ACR50 and 70, both SEC doses showed the same pattern of significance as for ACR20. Sensitivity analyses using the mixed population were in general agreement with these observations. For PASI50, 75, and 90 at weeks 12–16 in the biologic-naïve population, only a small evidence network with SEC, GOL 50/100mg, adalimumab 40 mg (ADA) and INF was available and there were no statistically significant differences between SEC and these comparators. In the mixed population, SEC was statistically significantly superior to ADA, APR 20/30 mg, certolizumab pegol (CZP) 200/400 mg, etanercept (ETN) 25/50 mg BIW and 50 mg QW, and (SEC 300 mg only) GOL 50 mg. Conclusions SEC shows statistically significantly higher results vs. UST and APR in ACR20, 50 and 70, with at least comparable response rates across all ACR and PASI endpoints vs. all therapies included in this NMA. For PASI50, 75, and 90 responses, SEC had high response rates with statistically significant results vs. ADA, APR, CZP, ETN, and (SEC 300 mg only) GOL 50 mg. Disclosure of Interest I. McInnes Consultant for: Novartis, Janssen, Abbvie, Pfizer and UCB, P. Nash Grant/research support from: Novartis, Consultant for: Novartis, C. Ritchlin Grant/research support from: Abbvie, Amgen, UCB, Consultant for: Amgen, Abbvie, Jannsen, Novartis, Sun Pharma, Sanofi, UCB, Boeringer Ingelheim, H. Thom Consultant for: Novartis Pharma AG and for a short time in 2015 for Eli Lilly, S. Kanters Consultant for: Novartis, E. Palaka Employee of: Novartis employee, K. Gandhi Shareholder of: Novartis, Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis

THU0448 Secukinumab for The Treatment of Psoriatic Arthritis: Comparative Effectiveness Results versus Adalimumab Up To 48 Weeks Using A Matching-Adjusted Indirect Comparison

Background Secukinumab (SEC) is approved for the treatment of active PsA in adults with inadequate response to DMARDs. The FUTURE 2 (F2) trial showed superiority of SEC 150 mg and 300 mg over placebo for the primary outcome of ACR20 response at week 24 and for multiple secondary outcomes, with efficacy sustained to week 52. The ADEPT trial compared adalimumab 40 mg (ADA) with placebo in biologic-naïve patients. In F2, patients could switch from placebo (from week 16); for both trials all had switched after week 24. In the absence of direct comparison or a continuous common placebo arm, matching-adjusted indirect comparison (MAIC) can assess relative efficacy. MAIC adjusts for differences in patient characteristics at baseline, reducing the effective sample size (ESS) for the therapy arm in one trial, but matching this with the population of the therapy arm from another trial, thus simulating head-to-head comparison. Objectives To assess the relative efficacy of SEC 150 mg and 300 mg vs. ADA using F2 and the published ADEPT trial. Methods Patient-level data from the SEC arms of the F2 trial (n=200 across SEC doses) were weighted to match patient baseline characteristics for the ADA arm of ADEPT (n=151). Logistic regression was used to determine weights for age, body weight, sex, race, methotrexate use, presence of psoriasis (≥3% body surface area), mean PASI score, dactylitis, enthesitis, mean HAQ-DI and previous biologic therapy. Weighted outcomes from F2 (ESS: n=36 for SEC 150 mg; n=38 for SEC 300 mg) were compared with data from ADEPT (both trials used non-responder imputation). Pairwise comparisons using relative risks (RRs) were performed and results are presented as RR (95% CI) and probability of response (95% CI) for ACR20, 50 and 70 at week 48. For PASI75 and 90, ADA week 48 results are compared with SEC week 52 data (the nearest data point). Results In the MAIC, both SEC doses had higher mean ACR20, 50 and 70 responses than ADA, with statistical significance for SEC 150 mg (RR: 1.41 [1.14–1.76], p=0.002) and SEC 300 mg (RR: 1.31 [1.03–1.66], p=0.027) at ACR20 and for SEC 300 mg (RR: 1.41 [1.03–1.92], p=0.032) at ACR50. The ACR20, 50 and 70 response rates were 79.6% (72–88), 57.1% (47–67) and 32.4% (23–42) respectively for SEC 150 mg; 73.5% (64–83), 61.4% (51–71) and 42.9% (33–53) for SEC 300 mg; and 56.3% (48–64), 43.7% (36–52) and 29.8% (23–37) for ADA. Findings were consistent across sensitivity analyses which also showed significance for SEC 300 mg at ACR70. PASI 75 and 90 response rates were numerically better for SEC 300 mg: 71.1% (57–86) and 52.2% (36–68) than ADA: 58.0% (46–70) and 46.4% (35–58). SEC 150 mg rates were 51.2% (38–64) and 40.8% (28–54) respectively. Conclusions When adjusted for patient baseline characteristics, SEC was associated with numerically higher response rates for joint and skin outcomes with statistically significantly higher responses vs. ADA for ACR endpoints at week 48. The next level of evidence will be a head-to-head to substantiate these findings. Disclosure of Interest P. Nash Grant/research support from: Novartis, Consultant for: Novartis, I. McInnes Consultant for: Novartis, Janssen, Abbvie, Pfizer and UCB, P. Mease Grant/research support from: Corrona, Speakers bureau: Corrona, Merck and Novartis, H. Thom Consultant for: Novartis Pharma AG and for a short time in 2015 for Eli Lilly, S. Cure: None declared, E. Palaka Employee of: Novartis, K. Gandhi Shareholder of: Novartis, Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis