Systemic antipsoriatic treatment: do women respond better than men and if so, why?
Authors: P. Wolf
Journal: British Journal of Dermatology (2021)

Linked Article: Maul et al. Br J Dermatol 2021; 185:1160–1168. Reports on antipsoriatic treatment responses specifically evaluating sex differences are scarce. Maul et al.1 undertook a major effort and now report from a two-country study on data of more than 5300 patients with moderate-to-severe psoriasis extracted from psoriasis registries of Germany (PsoBest) and Switzerland (SDNTT). These registries are fed by data from 880 office-based dermatology practices and academic or hospital-based outpatient clinics in Germany and eight academic dermatology departments in Switzerland. The investigators report slight but statistically significant better response rates throughout the 12-month observation period of the study in women compared with men, who started their treatments with slightly higher Psoriasis Area and Severity Index (PASI) score. After 12 months, 72·3% of women vs. 66·1 of men not only reached PASI75 reduction or an absolute PASI of ≤ 3 but also in parallel, a significantly higher proportion of women experienced a better quality of life during the observation period, measured by improvement of the Dermatological Quality of Life Index (DLQI) score of ≥ 4 in 70·7% of women vs. 64·4% men. Of importance to note, the range of percentages of women and men (40·4% vs. 59·6%) in this analysis were similar to that in other registry reports.2, 3 However, at treatment baseline, women not only had a lower PASI score than men (13·1 vs. 14·9), consistent with previous work,4 but also were slightly older (48·3 vs. 47·1 years) and had less body weight (77·5 vs. 90·9 kg), although their body mass index was nearly identical (28·2 vs. 28·5 kg m–2). With regard to treatment allocation, the majority of patients (71·6% of women and 69·4% of men) in this two-country analysis had received nonbiologic agents, i.e. mainly fumaric acid esters and methotrexate although the latter drug was administered less often in women than in men (4·4% vs. 15·8%). The biologics administered to the remaining smaller portion (around 30%) of patients included etanercept, infliximab, adalimumab, ustekinumab and secukinumab. Going beyond hormonal status, how could these differences in treatment response between women and men be explained, even if, as pointed out by the investigators, the lower weight of women compared with men, and based on sex- and weight-independent standard dosing, a relatively higher dosing of drugs in women could have contributed to improved effectiveness? Alternatively, or additionally, different patient needs5 and/or a better drug adherence might have contributed to a better outcome, comparing women and men. Intriguingly, however, previous studies have indicated that female sex was associated with an increased risk of stopping biologic treatment, including tumour necrosis factor antagonists, ustekinumab and anti-interleukin (IL)-17 antibodies,2, 3, 6-8 as revealed by drug-survival analysis, a concept coined for treatment outcome in psoriasis by Gniadecki and colleagues.6, 9, 10 However, drug survival does not only incorporate drug effectiveness but also safety, reimbursement, availability of alternative treatment options and expectations of physicians and patients. Moreover, previous work has revealed that drug survival correlated directly with clinical effectiveness for certain drugs such as adalimumab and etanercept.2 How this can be reconciled with the observed higher response rates in women compared with men needs to be addressed in future studies. Furthermore, as the two-country analysis by Maul et al.1 was predominated in terms of numbers by patients treated with fumaric acid esters and methotrexate, future studies with real-life data will have to address whether the observed better response rates in women also hold in general for biologics, and in particular for the latest generation, i.e. anti-IL-17 or IL-23p19 antibodies. Peter Wolf: Conceptualization (lead); Writing-original draft (lead).