This meta-analysis was registered with PROSPERO (CRD42024538548). This study adhered to PRISMA guidelines13 (Supplementary file 1).

The research question was formulated according to the PICOS strategy:

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  P (Population): Adult patients aged 18 years and older who had been diagnosed with HS.

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  I (Intervention): Anti-interleukin 17 treatments.

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  C (Comparator): Placebo therapy.

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  O (Outcome): The primary outcome of interest was the safety and efficacy profile of anti-IL17 treatments in patients with HS. This included the metrics of Hidradenitis Suppurativa Clinical Response (HiSCR), including HIiSCR75 and HiSCR90, Dermatology Life Quality Index (DLQI) as a Patient-Reported Outcome Measure (PROM), the incidence rate of patients with adverse events, serious adverse events, headache, infections and infestations of any organs, candida infections, inflammatory bowel disease and treatment withdrawal.

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  S (Study design): Only randomized placebo-controlled clinical trials were eligible for inclusion.

Exclusion criteria were applied to ensure the quality and comparability of the included studies. Observational studies, both case-control and cohort studies, were excluded. Systematic reviews and literature reviews were excluded too. Duplicates: Multiple reports on the same study were excluded to avoid duplication of data.

An extensive literature review was conducted using multiple databases, including PubMed, Scopus, and the Cochrane Central Register of Controlled Trials from inception until June 9th, 2024 (Fig. 1). A systematic and rigorous methodology was used to search for relevant studies, without establishing a specific time OR, language limit. A thorough review of the bibliographic references of the selected studies in the first phase of the search was conducted to identify any additional studies that might have been omitted from the initial search.

Figure 1.

Study selection flow diagram (Preferred Reporting Items for Systematic reviews and Meta-Analysis).

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We used the following search terms to search all trial registers and databases: (hidradenitis suppurativa OR, acne inversa) AND (IL-17 OR, IL17A OR, bimekizumab OR, secukinumab) (Supplementary file 2). Two reviewers (AO/ML) independently agreed on the selection of eligible studies and reached a consensus on the studies that should be included.

Two authors (AO/ML) independently reviewed the data extracted from the studies. If consensus was not reached, a third author, (CM) was consulted to complete the data-extraction form. The following data were collected: baseline characteristics of the articles, author, and year of publication, study type, clinical trial identifier, study design, primary endpoint in weeks, severity, sample size, age, number of women, outcomes and conflicts of interest related to the pharmaceutical industry.

In RCTs involving more than one arm with an anti-IL17, each of them was analyzed separately.

One of the compared variables was the HiSCR, at 2, 4, 12 and 16 weeks. HiSCR is an endpoint regardless of lesion size, pain or impact on quality of life. It is defined as, at least, a 50% reduction in the total abscess and inflamatory nodules count with no increase in abscess count or draining tunnel count relative to baseline.14 Efficacy data were extracted at weeks 2 and 4 to assess speed, and efficacy data were extracted at weeks 12 and 16 since these were the endpoints of the studies. HiSCR75 and HiSCR90 values were also extracted if reported. As PROM, the mean change and its standard deviation of the DLQI was extracted if reported by the studies. For safety outcomes, comparisons could be drawn using the incidence rate of patients with adverse events, serious adverse events, headache, infections and infestations of any organs, candida infections, inflammatory bowel disease and treatment withdrawal.

The methodological quality and risk of bias (RoB) of the included RCTs were independently evaluated by 2 reviewers using the Cochrane Collaboration's risk of bias tool (Review Manager software). This tool systematically assesses 6 key domains related to bias: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. For each domain, explicit prespecified criteria were used to assign ratings of low, high, or unclear RoB. The results of the RoB are shown in Fig. 2 and the justification for each criterion can be consulted in the Supplementary file 3.

Figure 2.

Risk of bias assessment (green=low risk; red=high risk; yellow=unknown).

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Mean differences (MD) and 95% confidence intervals (CI) were estimated for continuous variables measured on the same scale. Odds ratios (OR) were calculated for the dichotomous variables. Heterogeneity was assessed using the I2 statistic, with values<25%, 25–50%, and >50% indicating low, moderate, and high heterogeneity, respectively. A fixed-effects model was used when no significant heterogeneity was observed. Incomplete data reporting across studies was addressed following methodological guidance from the Cochrane Handbook.15 Review Manager 5.4 statistical software was used for all analyses. Web-PlotDigitizer version 4.7 was used to obtain information from the figures in the articles. A level of threshold of statistical significance was considered if P<0.05.

Funnel plot analysis was conducted using Review Manager 5.4 software to assess potential reporting bias. Funnel plot asymmetry can suggest a publication bias arising from the non-publication of smaller studies with null or, inconclusive findings.

Subgroup analyses were performed based on follow-up time in case of HiSCR, specifically at 2, 4, 12 and 16 weeks, and based on different adverse event variables in the safety outcomes.

Due to interest in real-world clinical practice, the safety and efficacy data for bimekizumab and secukinumab have been analyzed separately.

Sensitivity analysis removing studies of non-commercialized drugs for each outcome and reanalyzing data was conducted using Review Manager 5.4 to assess the robustness of the results and evaluate the impact of excluding individual studies on the overall interpretations.

The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, utilizing GRADEpro, was used to assess the certainty of the outcomes.16 GRADE evaluates the quality of evidence based on factors such as study design, RoB, inconsistency, indirectness, imprecision, and publication bias. Data used were those entered in Review Manager 5.4.

The initial search yielded a total of 320 articles from databases. After removing duplicates and reviews based on titles and abstracts, a total of 256 articles were excluded, resulting in 64 articles. After reviewing the full texts, 60 studies were excluded for not meeting the inclusion criteria. Finally, 4 studies were included in the systematic review and meta-analysis10–12,17 (fig. 1).

Table 1 illustrates the main characteristics of the included studies. Two articles reported on 2 different clinical trials each. Four articles with 2231 patients were included (1668 from the anti-IL17 group and 563 from the placebo group). All studies included were randomized placebo-controlled clinical trials. The number of women was generally higher compared with men in the studies. The patients’ mean age in the studies is shown in Table 1. The severity of HS in all studies was moderate-to-severe. Only data from the first period of the clinical trials were exported to avoid overall bias and period effect.

The RoB of the first period of each clinical trial was analyzed. The RoB results are shown in Fig. 2. In clinical trial NCT02421172, random sequence generation and allocation concealment were scored with “unclear risk of bias” since they were not detailed. It was marked as “high risk of bias” in blinding of outcome assessment because it was not reported. For the rest of the studies a low risk of bias was considered.

Treatment with anti-IL17 in HS showed a higher percentage of patients achieving HiSCR significantly vs placebo (OR, 1.96 [1.79–2.15]). Analyzed by weeks, a higher percentage of patients achieved HiSCR from week 2 (OR, 1.90 [1.52–2.38]) to week 4 (OR, 2.15 [1.79–2.59]), week 12 (OR, 2.04 [1.72–2.42]) and week 16 (OR, 1.78 [1.51–2.11]) (Fig. 3). Regarding the HiSCR75 variable, treatment with anti-IL17 showed a significantly higher percentage (OR, 2.46 [1.77,3.43]) of patients achieving this response vs placebo, but not so much for the HiSCR90 variable (OR, 1.49 [1.00,2.21]) (Fig. 4). Regarding PROM, treatment with anti-IL17 showed a significantly greater decrease in DLQI (MD −1.92 [−2.68 to 1.16]) (Fig. 5).

Figure 3.

Forest plots showing subgroup analysis in relation to weeks 2, 4, 12, and 16 since first drug administration (total analysis included as well).

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Figure 4.

Forest plots of patients who achieved HisCR75 (a) and HiSCR90 (b).

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Figure 5.

Forest plot showing the mean and standard deviation of changes in DLQI in the studies that reported this variable quantitatively.

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Treatment with anti-IL17 showed a significant increase in adverse effects vs placebo; OR, 1.21 [1.09, 1.34]. No differences were found regarding the number of patients experiencing adverse events; OR, 1.02 [0.86–1.20]. There were no significant differences in serious adverse events (OR, 1.14 [0.68–1.92]), headache (OR, 1.17 [0.87–1.56]), development of inflammatory bowel disease (OR, 2.06 [0.50–8.48]) or in the rate of adverse event-related treatment withdrawal (OR, 1.90 [1.00–3.59]). Significant differences were found regarding a higher rate of infections and infestations of any organ (OR, 1.23 [1.03–1.46]) and Candida infections (OR, 5.61 [2.66–11.83]) with the use of anti-IL17 vs placebo (Table 2 and Supplementary file 4).

A separate analysis of the safety and efficacy results for bimekizumab and secukinumab is shown in Table 3 and Supplementary data 5. In terms of efficacy, the results of bimekizumab with respect to obtaining HiSCR show an OR>2 two weeks into therapy, with a total OR of 2.30 [1.98, 2.69], with respect to the total OR of secukinumab (1.83 [1.63, 2.06]), whose results are lower on the subanalyses conducted on weeks 2, 4, 12 and 16. However, regarding safety variables, secukinumab shows no difference with respect to placebo regarding the rate of adverse effects (OR, 1.04 [0.91, 1.19]), including candidiasis (2.22 [0.84, 5.87]) vs an increase in adverse effects vs placebo with the use of bimekizumab (OR, 1. 55 [1.30,1.85]), with significant differences being due to a greater increase in infections and infestations of any organ (OR, 1.96 [1.44–2.67]), mainly candidiasis (OR, 11.64 [3.25–41.68]), and treatment withdrawal due to adverse effects (OR, 3.35 [1.09–10.27]).