Network Meta-Analysis To Evaluate The Efficacy of Ixekizumab In The Treatment of Moderate-To-Severe Psoriasis

Abstract

Objectives: Graft-versus-host disease (GVHD) is a severe complication of allogenic stem cell transplantation. Preliminary data suggest the potential role of ruxolitinib as a new treatment option in patients with corticosteroid-refractory GVHD. The aim of the present study was to explore the effectiveness and safety of ruxolitinib as a salvage therapy in this population. MethOds: A single-center, retrospective, observational study was carried out. Inclusion criteria: all patients with corticosteroidrefractory GVHD treated with ruxolitinib until June 2016. Collected variables: age, sex, underlying disease, GVHD location, type (acute or chronic) and grade, previous therapies, Eastern Cooperative Oncology Group (ECOG) performance status at baseline, daily dose of ruxolitinib, treatment response and grade ≥ 3 adverse events (AE). Data sources: pharmacy information system and clinical charts review. Results: 13 patients met the inclusion criteria. 46% were male, with a median age of 46 years (range:32-51). The majority of patients (77%) had an ECOG performance status = 1. The most frequent underlying condition was myeloid acute leukemia. Most of the patients (77%) had more than one part of the body affected, being the most affected the cutaneous and gastrointestinal locations. GVHD was chronic in 62% of patients, and 54% had grade ≥ 3 GVHD. The median number of previous GVHD-therapies was 3 (range: 3-5). The most frequency therapies were corticosteroids, inmmunosuppression therapies with tacrolimus and rapamycin, and photopheresis. The median daily dose of ruxolitib was 20 (range: 5-25) mg. The overall response rate was 77% (complete response: 23%, partial response: 54%). Esophageal affectation in one patient was the only AE ≥ 3 recorded. cOnclusiOns: Ruxolitinib appears to be an effective and safe treatment option for patients with GVHD who are refractory to corticosteroids and other available therapies. Randomized control trials are needed to confirm these promising results.

Matching-adjusted indirect comparison of efficacy in patients with moderate-to-severe plaque psoriasis treated with ixekizumab vs. secukinumab

“…For the previously reported SLR (data collected from January 1990 to November 2015, with an update from November 2015 to November 2016) the following databases were searched in Ovid: Embase, Ovid MEDLINE, Ovid MEDLINE Daily Update, Ovid MEDLINE In‐Process & Other Non‐Indexed Citations, PsycINFO, Econlit, ACP Journal Club, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Cochrane Methodology Register, Database of Abstracts of Reviews of Effects, Health Technology Assessment, NHS Economic Evaluation Database and Database of Abstracts of Reviews of Effects. This analysis was carried out for previously reported NMAs; of the seven secukinumab studies identified, five met the criteria for selection in this MAIC.…”

“…The systematic literature review (SLR) was performed in line with recommended guidelines from the Cochrane Handbook of Systematic Reviews of Interventions. 15 For the previously reported SLR (data collected from January 1990 to November 2015, with an update from November 2015 to November 2016) 10…”

“…Although an indirect comparison is not a replacement for a head‐to‐head trial, accuracy is improved when a common active comparator is used with a method such as the previously described matching‐adjusted indirect comparison (MAIC), which combines published and patient‐level data that are matched for baseline characteristics . Because the MAIC uses individual patient data (IPD), this approach is complementary to and can reduce biases found in network meta‐analyses (NMAs), which have limitations that have been described elsewhere . Matching on baseline characteristics helps to reduce imbalances from different trials that might impact the outcome (treatment effect modifiers) .…”

“…9 Because the MAIC uses individual patient data (IPD), this approach is complementary to and can reduce biases found in network meta-analyses (NMAs), which have limitations that have been described elsewhere. [10][11][12][13] Matching on baseline characteristics helps to reduce imbalances from different trials that might impact the outcome (treatment effect modifiers). 9 Thus, if IPD is available and there is an imbalance regarding known effect modifiers that may impact the results across trials (especially across IPD and published trials), MAICs might be preferred over adjusted indirect comparisons (AICs) or NMAs.…”

Long‐term efficacy of novel therapies in moderate‐to‐severe plaque psoriasis: a systematic review and network meta‐analysis of PASI response

“…8 The technique borrows strength from indirect evidence to enable the simultaneous evaluation of relative effects that have not been investigated directly in RCTs 9 and has been used extensively to evaluate short-term effects of psoriasis treatments. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] The objective of this study was to compare novel systemic therapies, both biologic and non-biologic, approved for the treatment of moderate-to-severe psoriasis by conducting a SLR and NMA of Psoriasis Area and Severity Index (PASI) outcomes measured at or around 1 year.…”