Hidradenitis suppurativa (HS) presents a considerable treatment challenge, and many patients remain with inadequate disease control despite the currently available therapeutic options. Recent advances in the therapeutic approach to HS have emerged with the development of cytokine inhibitors and small molecule drugs. These advancements are largely due to a deeper understanding of the disease's pathophysiology, especially the role of the Th17 inflammatory pathway.1,2 Currently, 2 IL-17 inhibitors, secukinumab and bimekizumab, have been approved for the treatment of HS, following positive outcomes in phase III randomized clinical trials.3,4 Additionally, other IL-17 inhibitors, including sonelokimab, izokibep, and CJM112, are currently being investigated in both phase II and phase III clinical trials.5–8

While clinical trials are essential for evaluating the safety and efficacy profile of new treatments, they are conducted under controlled conditions with carefully selected patient populations. This controlled environment often does not fully represent the broader and more diverse patient populations encountered in everyday clinical practice. As a result, the findings from these trials may not always be generalizable to real-world settings. Real-world studies, on the other hand, include a broader range of patients and reflect the complexities and variability of actual clinical practice, potentially offering more relevant and applicable information for routine care. This evidence is crucial for bridging the gap between clinical trial results and the actual effectiveness and safety of treatments in diverse patient populations.9,10

Even before the official approval of secukinumab and bimekizumab, these drugs were used in real-world clinical practice as compassionate options for patients resistant to adalimumab, due to the limited therapeutic alternatives available.11–13 Following their approval, ongoing studies continue to evaluate their effectiveness and safety in real-world settings.

The aim of this study is to systematically review and analyze the available real-world evidence (RWE) on the safety and efficacy profile of secukinumab and bimekizumab in patients with HS through a comprehensive systematic review and meta-analysis of the current literature.

This systematic review compiles the available evidence on the use of the 2 IL-17 inhibitors approved for the treatment of HS, secukinumab and bimekizumab, in real-world clinical practice. A total of 13 studies were included, involving 292 HS patients on secukinumab and 55 patients on bimekizumab. Of those on secukinumab, the meta-analysis found that 50.31% achieved HiSCR at the longest follow-up available. Patients on bimekizumab showed significant reductions in IHS4 and pain VAS scores, among other measures.

Although bimekizumab and secukinumab are both IL-17 inhibitors, they differ in their mechanisms of action: bimekizumab inhibits both IL-17A and IL-17F, while secukinumab targets only IL-17A. Although IL-17F is a weaker inducer of proinflammatory cytokines, it is upregulated in early and chronic HS lesions, contributing to ongoing inflammation. Bimekizumab dual inhibition is theorized to provide better control of inflammation in HS compared to secukinumab.31 However, a direct comparison of the efficacy between bimekizumab and secukinumab is not currently possible, as no head-to-head studies have been conducted.

This review suggests that while both drugs may offer similar benefits, the significant imbalance in the number of studies and patients treated with each drug limits meaningful comparisons. Of the 13 studies reviewed, 11 focused on secukinumab, while only 2 examined bimekizumab, which reduces the generalizability of conclusions about bimekizumab. Consequently, the current evidence is insufficient to determine their comparative effectiveness. Future research should address this gap by conducting direct comparisons to identify specific patient populations or clinical scenarios where one drug may provide superior outcomes.

Overall, real-world data on IL-17 inhibitors for treating HS remains limited, particularly due to the small sample sizes of the included studies. This limitation is understandable given the low prevalence of HS and the relatively recent adoption of these therapies. Despite their small scale, these studies provide valuable insights into how IL-17 inhibitors are used in everyday clinical practice, offering a complementary perspective to that of RCTs.

Another important point that should be taken into consideration is that RCTs and RWE studies have several key distinctions. SUNNY and BE HEARD trials established both minimum and maximum thresholds for the number of inflammatory lesions, whereas most RWE studies did not impose such criteria. Another major difference lies in the severity of HS among patients: most participants in the RCTs had moderate HS, classified as Hurley II (59.04% in SUNNY and 55.72% in BE HEARD trials). In contrast, RWE studies predominantly included patients with severe HS, classified as Hurley III (52.85% in secukinumab studies and 70.9% in bimekizumab studies). The most notable difference, however, is the previous exposure to biologic therapies. In the RCTs, most patients were biologic-naive, with only 24% in the SUNNY and 19% in the BE HEARD trials having prior exposure to a biologic drug. On the other hand, about 90% of patients from the RWE studies had previously received at least one biologic agent for HS, with most experiencing treatment failure or, less frequently, adverse events. Patients included in RWE studies generally had more severe disease and had previously failed at least one biologic therapy, which may suggest reduced treatment effectiveness compared with patients enrolled in RCTs However, the efficacy profile reported is quite similar. In the SUNNY trials, HiSCR rates at week 16 ranged from 42% to 46%, comparable to the rates reported in the RWE studies. Notably, RWE studies on bimekizumab did not use HiSCR to report the drug's efficacy, which limits direct comparison with the results from the BE HEARD trials, where HiSCR was 45–54% at week 16.3,4

Although HiSCR has become a widely used tool for assessing treatment efficacy in HS, it has some limitations.32,33 It defines a response as a 50% reduction in abscesses and nodules, dynamic lesions that may resolve spontaneously over time. As a result, HiSCR might categorize a patient as responder merely because their acute lesions have diminished, while ignoring persistent, static lesions such as draining tunnels. This may contribute to the observed high rates of HiSCR responses in patients receiving placebo in RCTs.3,4 Additionally, HiSCR only measures changes at specific timepoints and does not reflect the overall course of the disease, which alternates between flare-ups and periods of stability. A new tool, the IHS4-55, defines a response as a reduction of at least 55% in the baseline IHS4 and addresses the issue of draining tunnels by including them and emphasizing their impact in the formula.34 However, IHS4-55 still does not capture the fluctuant course of HS. A recently proposed tool, the cumulative-IHS4, aims to address this by considering the number of lesions over the entire evaluation period rather than at specific timepoints. Nevertheless, this tool requires further evidence and validation.35

Biologic drugs alone often do not provide sufficient control of the disease. Adjuvant therapy, such as systemic antibiotics for flare-ups, incision and drainage or intralesional corticosteroid injections for isolated symptomatic lesions, and surgery for tunnel removal, are often necessary.36,37 However, most of the studies reviewed did not specify whether patients received these additional therapies alongside the IL-17 inhibitor. In contrast, the SUNNY and BE HEARD trials allowed concomitant therapies, either chronic or as bailout treatments.3,4 The use of these additional therapies complicates the evaluation of the biologic drug efficacy profile, as capturing and analyzing the data becomes challenging and there is no standardized method for assessing effectiveness when adjunctive treatments are involved.

Regarding the safety profile, IL-17 inhibitors are generally well-tolerated. Common side effects observed in both RCTs and RWE studies included upper respiratory infections, headaches, and oral candidiasis.3,4 These side effects are usually mild and manageable with standard treatments, rarely requiring discontinuation of the medication. Inflammatory bowel disease (IBD) cases were reported in both RWE studies (3 cases) and RCTs (10 cases). Patients with HS are already at a higher risk for IBD, and IL-17A inhibition has been associated with this condition.38–41 Since IBD can be a serious issue that often requires stopping the IL-17 inhibitor, careful monitoring for this side effect is essential.

An important source of heterogeneity among the reviewed studies was the time of response assessment, which ranged from 12 to 52 weeks. This variability makes it challenging to compare studies and draw clear conclusions about the overall effectiveness of IL-17 inhibitors. Additionally, most studies evaluated efficacy 16–24 weeks into therapy, which may not be sufficient to fully assess the long-term response to IL-17 inhibitors.

Another important aspect is how studies handled missing data from patients who did not complete follow-up. When patients drop out or discontinue the drug, often due to lack of efficacy, there are 2 main approaches to account for these cases: include the entire study population by carrying forward the last recorded data, or only include patients who completed follow-up. Excluding patients who stopped treatment early, potentially due to inefficacy, could result in inflated response rates. In our meta-analysis, HiSCR was calculated using the initial sample size of each study, treating patients who did not complete follow-up as non-responders. This method provides a more conservative estimate of treatment efficacy by acknowledging that discontinuation may be due to inefficacy. However, it assumes that all patients who did not complete the study are non-responders, which may not fully reflect their actual response.

As discussed earlier, this review has several limitations, including the limited number of studies examining bimekizumab, small sample sizes, variability in outcome measures, different time of response assessments, varying methods for handling missing data, and insufficient information on adjuvant therapies used along the biological drug. These factors limit the ability to synthesize evidence effectively and affect the overall quality of the results.

In conclusion, the findings from RWE studies fairly align with those from RCTs. Although IL-17 inhibitors show moderate response rates, not achieving the success observed in other inflammatory diseases, they can be considered a valuable therapeutic option for patients refractory to other treatments. These drugs generally have a low rate of adverse events, which are usually mild. Some remaining issues to be addressed include identifying specific disease types or patient profiles most likely to benefit from these drugs and developing outcome measures that accurately capture all treatments used and reflect disease control over the entire treatment period.

The authors declare that they have no conflict of interest.