Patient characteristics as effect modifiers for psoriasis biologic treatment response: an assessment using network meta-analysis subgroups

Background Network meta-analyses (NMAs) of psoriasis treatments, undertaken as part of the NICE Single Technology Appraisal (STA) process, have included heterogeneous studies. When there is inconsistency or heterogeneity across the different comparisons or trials within the network of studies, the results of the NMA may not be valid. We explored the impact of including studies with heterogeneous patient characteristics on the results of NMAs of psoriasis treatments. Methods All NMAs undertaken for psoriasis STAs were identified and the included studies tabulated, including patient characteristics that may influence relative treatment effects. In addition to the original network of all studies using licensed treatment doses, a range of smaller, less heterogeneous networks were mapped: 'no previous biologic use' (< 25% patients had prior biologic therapy exposure), 'Psoriasis Area and Severity Index score <= 25', 'weight <= 90 kg' and 'white ethnicity' (>= 90% patients were white). Results Sixty-nine studies were included in our synthesis (34,924 participants). A random effects model with a log-normal prior distribution was chosen for each of the subgroup NMAs. Heterogeneity was reduced for the four smaller networks. There were no significant differences in the relative treatment effect (PASI 75 response) for each treatment across the five NMAs, with all credible intervals overlapping, although there were noticeable differences. Treatment rankings based on the median relative risks were also generally consistent across the networks. However, the NMA that included only studies in which < 25% patients had prior biologic therapy exposure had slightly different treatment rankings; the anti-TNF therapies certolizumab pegol and infliximab ranked higher in this network than any other network, although credible intervals were large. Conclusions This work has highlighted potential differences in treatment response for biologic-naive patients. When conducting NMAs in any area, heterogeneity in patient characteristics of included trials should be carefully assessed and effect modification related to certain patient characteristics investigated through clinically relevant subgroup analyses.