Decision-Analytic Modeling for Time-Effectiveness of the Sequence of Induction Treatments for Moderate to Severe Plaque Psoriasis

Abstract

IMPORTANCE Systemic psoriasis treatments vary in efficacy and cost but also in time until onset of action. Patients with no response to a first induction treatment are typically switched to another, and some patients require several treatments before they see an improvement. OBJECTIVE To determine the most cost-effective sequence of induction treatment through a comparative time-effectiveness analysis of different systemic treatment sequences currently licensed in Germany for moderate to severe plaque psoriasis. DESIGN, SETTING, AND PARTICIPANTSThis time-effectiveness analysis used a decision-analytic model set in the German health care system. The population simulated to receive the treatment sequences consisted of adult men and women with psoriasis vulgaris or plaque type psoriasis eligible for systemic treatment. Systematic reviews were performed to generate model input values. Data were collected from November 1 through December 15, 2017, and analyzed from January through August 2018.INTERVENTIONS Five treatment sequences frequently used in Germany, identified through an online expert survey (response rate, 10 of 15 [66.7%]), and 4 theoretical sequences starting with a biological agent. Treatments included methotrexate sodium (MTX), cyclosporine (CSA), fumaric acid esters (FAE), adalimumab (ADA), ixekizumab (IXE), infliximab (INF), and secukinumab (SEC).MAIN OUTCOMES AND MEASURES Two health states were defined: responder (patients achieving a Psoriasis Area Severity Index [PASI] Ն75) and nonresponder (PASI <75). Probability values were defined as response rates of PASI-75. Treatment effects were determined by the mean change in Dermatology Life Quality Index (DLQI) score. Time until onset of action was assessed as weeks until 25% of patients reach PASI-75. Individual time-effectiveness ratios were calculated per treatment sequence as time until onset of action (in weeks) per minimally important difference (MID) in DLQI and were subsequently ranked. RESULTSTreatment sequences starting with a biological agent, including IXE-INF-SEC (1.4 weeks per DLQI-MID), INF-IXE-SEC (2.05 weeks per DLQI-MID), SEC-IXE-ADA (2.1 weeks per DLQI-MID), and ADA-IXE-SEC (2.8 weeks per DLQI-MID) were more time-effective than frequently used treatment sequences, including MTX-SEC-ADA (6.8 weeks per DLQI-MID), MTX-ADA-IXE (7.0 weeks per DLQI-MID), MTX-ADA-SEC (7.2 weeks per DLQI-MID), MTX-FAE-ADA (10.05 weeks per DLQI-MID), and FAE-MTX-CSA (11.5 weeks per DLQI-MID). The results were robust to deterministic sensitivity analyses.CONCLUSIONS AND RELEVANCE When allocating monetary resources, policy makers and regulators may want to consider time until patients experience an MID in their quality of life as an additional outcome measure.

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris – Part 1: treatment and monitoring recommendations

“…26 Sequential combination of slow acting drugs with low response rates carries a risk of long patient 'waiting times', until a noticeable, clinically meaningful improvement in their health-related quality of life. 27…”

“…Looking at the proportion of patients dropping out of clinical trials due to a lack of efficacy as a proxy, a strong increase in the rate of dropouts was seen after 10–12 weeks 26 . Sequential combination of slow acting drugs with low response rates carries a risk of long patient ‘waiting times’, until a noticeable, clinically meaningful improvement in their health‐related quality of life 27 …”

German S3‐Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm – Part 1: Treatment goals and treatment recommendations

“…This shows that the greatest increase in the rate of dropouts due to a lack of efficacy was seen after 10–12 weeks [10]. Sequential combination of slow acting drugs with low response rates carries a risk of long patient “waiting times”, until a noticeable, clinically meaningful improvement in their health‐related quality of life [11].…”

Choosing a biologic for psoriasis: is it a sprint or a marathon?

“…[5][6][7] Similarly, a study examining the time-effectiveness of simulated induction sequences revealed that initiating treatment with ixekizumab resulted in the shortest time to achieving a clinically significant reduction in dermatology life quality index (DLQI) for 25% of patients (1Á4 weeks). 8 However, to place these findings in context, a recent update of a Cochrane NMA of overall clinical effectiveness, rather than speed of action, in achieving ≥ 90% reduction in their Psoriasis Area and Severity Index score (PASI 90) in the induction phase (8-24 weeks), established that infliximab, all the IL-17 inhibitors (ixekizumab, secukinumab, bimekixumab and brodalumab) and IL-23 inhibitors (risankizumab and guselkumab, but not tildrakizumab) were similar in efficacy. 9 In this issue of the BJD, Blauvelt et al report on the 12-week results of a novel head-to-head 24-week trial comparing ixekizumab with guselkumab (IXORA-R).…”

“…Rapidity of clearance has been the focus of two recent network meta‐analyses (NMAs) and a systematic review, which conclude that ixekizumab and brodalumab, two agents that inhibit interleukin (IL)‐17A, are the fastest‐acting treatments when compared with other biologics and conventional systemic agents . Similarly, a study examining the time‐effectiveness of simulated induction sequences revealed that initiating treatment with ixekizumab resulted in the shortest time to achieving a clinically significant reduction in dermatology life quality index (DLQI) for 25% of patients (1·4 weeks) . However, to place these findings in context, a recent update of a Cochrane NMA of overall clinical effectiveness, rather than speed of action, in achieving ≥ 90% reduction in their Psoriasis Area and Severity Index score (PASI 90) in the induction phase (8–24 weeks), established that infliximab, all the IL‐17 inhibitors (ixekizumab, secukinumab, bimekixumab and brodalumab) and IL‐23 inhibitors (risankizumab and guselkumab, but not tildrakizumab) were similar in efficacy …”