The Impact of Methodological Approaches for Presenting Long-Term Clinical Data on Estimates of Efficacy in Psoriasis Illustrated by Three-Year Treatment Data on Infliximab

Abstract

Background: Psoriasis affects about 2–3% of the Caucasian population. Biologics such as infliximab, etanercept, adalimumab and ustekinumab are efficacious treatments of plaque-type psoriasis. Critical to monitoring drug efficacy and safety is availability of long-term data. Despite the chronic nature of psoriasis, to date limited long-term clinical data have been available, as challenges are inherent in conducting a long-term analysis. With increasing time, it is more likely that the number of patients discontinuing treatment will also increase, due to loss of efficacy, adverse events or loss to follow-up. Interpretation of these data becomes confounded when one must consider missing data. Several approaches to analysing long-term data exist, and each accounts for missing data differently. Objective: To demonstrate that the choice of a particular analysis method to account for missing data has great impact on the assessed response rate. Methods: We used data from an open-label study over 3 years of continuous treatment with infliximab in patients with plaque-type psoriasis. These data were analysed by three methods – last observation carried forward, observed values and non-responder imputation – to account for missing data. Results: The 3-year PASI 75 responses varied from 41 to 75%, depending on the method of analysis; this shows that the response rate can almost double when a more liberal analytical approach is used. Conclusions: While it is clear that the need for long-term data on biologics in psoriasis is great, considering the analysis undertaken is important when designing long-term studies and interpreting the resulting data. When analysis methods such as observed values only or last observation carried forward are used, the results of the more conservative non-responder imputation should also be presented to give a fair overview of the long-term efficacy of a treatment for plaque-type psoriasis.

Prevalence and Management of Panic Attacks during Infliximab Infusion in Psoriatic Patients

“…In accordance with our clinical experience [30], in cases where panic attacks have occurred with previous infusions, we suggest a premedication with oral benzodiazepine, a slow rate of infusion and, if needed, psychological and psychiatric support.…”

Efficacy and safety of systemic treatments for moderate‐to‐severe psoriasis: meta‐analysis of randomized controlled trials

“…The use of different imputation models can have an important impact on the results. 65,67 When interpreting the results of this meta-analysis it should also be considered that the trials included in this review have been undertaken over a period of about two decades. The populations included in trials 20 years ago and today may differ in important characteristics such as body weight and previous exposures to systemic anti-inflammatory agents, which may add some heterogeneity and is one reason why we generally used random effects meta-analysis.…”

Results of three analytical approaches on long-term efficacy of etanercept for psoriasis in daily practice

“…4,5 The ITT analysis with (modified) nonresponder imputation approach may give a toonegative view of the efficacy of etanercept. On the other hand, the as-treated analysis introduces a bias towards a too-positive outcome.…”