First real‐world data provide evidence for a ‘window of opportunity’ in treatment of hidradenitis suppurativa/acne inversa
Authors: C.C. Zouboulis
Journal: British Journal of Dermatology (2020)

Linked Article: Marzano et al. Br J Dermatol 2021; 184:133–140. Drug registrations require a standardized sequence of randomized controlled trials (RCTs). In an effort to reduce certain sources of bias when testing the effectiveness of new treatments, RCTs may, to some extent, exclude patients who could jeopardize the efficacy and safety results. However, the excluded patients are often the exact 'difficult' patients for whom physicians expect results from new treatments. Furthermore, the inclusion criteria in studies of hidradenitis suppurativa/acne inversa (HS) may not consider clinically important patient groups that could benefit from the use of new treatments through prevention of progression to irreversible scarring disease. Finally, it is of great importance to use validated scoring systems to assess eligibility for inclusion in RCTs, in order to capture these patient groups as much as possible. The urgent need for information, which cannot be provided by RCTs through the restrictions mentioned above, has led to the collection of real-world data, which are provided by a number of sources that are associated with outcomes in heterogeneous patient populations in real-world settings, such as patient surveys, clinical trials and observational cohort studies.1 Real-world data are data that are collected outside of RCTs.2 They are gaining increasing attention for their use in regulatory decision making. Recently, investigators from the European Medicines Agency (EMA) recommended that in order to make the novel analytical methods currently introduced for evaluation of real-world data and patient-level data acceptable for regulators and other decision makers, testing and validation should be performed in broadly the same way as for RCTs.3 On the other hand, scientific journals still seem to be sceptical about the scientific value and suitability for publication of real-world data without a specialized expert review process.4 Interestingly, real-world data have already been used by the EMA to approve several medicines for rare or orphan indications.1 HS is exactly such a disease, for which RCTs may have excluded, up to now, a considerable number of patients such as those with very severe disease, patients with no scarring component at baseline, patients with considerable comorbid conditions, such as cardiovascular abnormalities,5 and patients previously treated with registered drugs of a similar pharmacochemical group. In an effort to close this gap, as reported in this issue of the BJD, Marzano et al. present their results of a retrospective and observational study with 389 patients with HS treated with adalimumab in 21 Italian centres in a real-world setting.6 Fulfilment of Hidradenitis Suppurativa Clinical Response (HiSCR) under adalimumab treatment was achieved by 170 patients (43.7%) at week 16, a result similar to that of the adalimumab registration studies PIONEER I (41.8% at week 12) and PIONEER II (58.9% at week 12).7 Moreover, the overall safety profile of adalimumab was excellent, with only mild reported adverse events, including transient asthenia, headache and nausea. Adalimumab discontinuation occurred in 14.9% of patients, mainly due to lack or loss of efficacy, a rate that is markedly higher than that in the PIONEER I and II studies (18 of 315, 5.7%).7 Interestingly, the 'therapeutic delay' correlated to lack of response to adalimumab at week 16 and was detected as a reliable parameter, predicting the clinical response to adalimumab in HS. Furthermore, inclusion criteria for RCTs up to now have included presence of a scarring component, so patients with Hurley stage I have been excluded. The use of validated outcomes for baseline severity, such as the International Hidradenitis Suppurativa Severity Score System (IHS4), which was used by Marzano et al., suggests that definition of moderate and severe disease does not require the presence of a scarring component, as Hurley staging suggests. The outcome of the study, together with the inverse correlation of achieved HiSCR with previous immunosuppressant treatment, provides evidence for a 'window of opportunity' suggesting that administration of adalimumab in early phases of HS should be highly encouraged. This also contradicts the registration of adalimumab as a second-line treatment after failure to respond to conventional systemic treatments (e.g. systemic antibiotics). Furthermore, this evidence provides a clear indication that the use of validates outcomes, such as IHS4, for defining the entry point to an RCT may be of substantial benefit. The proposed diversified procedure might reduce work loss, as well as direct and indirect costs of HS treatment.8 The Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany, are healthcare units of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin).