Hidradenitis suppurativa (HS) is a persistent and recurring inflammatory condition that typically manifests during early adulthood, with an estimated prevalence of about 1%. The progression of this disorder is characterized by repeated episodes of inflammatory nodules, abscesses, and the formation of draining tunnels, which can lead to significant scarring and irreversible damage to the affected tissues.
In addition to its cutaneous symptoms, HS is linked to systemic inflammation and carries a significant burden of metabolic and cardiovascular comorbidities. These factors contribute to considerable morbidity and can lead to a reduced life expectancy for those affected (Source: Cartron A, Driscoll MS, Comorbidities of hidradenitis suppurativa: A review of the literature). The management of moderate to severe HS remains a complex challenge, often necessitating long-term treatment strategies.
Several biologic therapies have received approval for the treatment of HS, including adalimumab, secukinumab, and more recently, bimekizumab. Although these therapies have shown positive results in clinical trials compared to placebo, there is a notable lack of direct head-to-head comparisons, particularly regarding long-term outcomes following the initial treatment induction phase.
Due to the scarcity of comparative data, clinicians and healthcare decision-makers face challenges when selecting appropriate treatment options over extended periods. A recent analysis has sought to bridge this knowledge gap by examining the longer-term relative efficacy of the approved biologic treatments for HS, employing a method known as matching-adjusted indirect comparison (MAIC).
The analysis was guided by a systematic review of the literature, conducted in accordance with PRISMA guidelines. This review identified randomized controlled trials assessing the licensed dosages of bimekizumab, secukinumab, and adalimumab in adults suffering from moderate to severe HS.
Trials that reported efficacy outcomes roughly at one year (week 48–52) were included. Ultimately, the analysis considered two trials for bimekizumab (BE HEARD I and II), two for secukinumab (SUNRISE and SUNSHINE), and three studies on adalimumab (PIONEER I, PIONEER II, and an open-label extension).
Since all included trials involved treatment switching post the initial placebo-controlled phase, there was no common comparator available for long-term follow-up. This situation necessitated the use of an unanchored MAIC. Individual patient data from the bimekizumab trials were reweighted to align with baseline characteristics reported in the comparator trials.
The matching variables considered included age, sex, race, body mass index, smoking status, counts of inflammatory nodules and draining tunnels, Hurley stage, and prior use of biologics. These factors were deemed clinically significant and potentially predictive of the treatment response.
Efficacy was assessed using widely accepted outcome measures for HS. These included the Hidradenitis Suppurativa Clinical Response (HiSCR), evaluated at various thresholds: ≥50%, ≥75%, ≥90%, and 100% reduction in inflammatory nodules and abscesses without exacerbation of abscesses or draining tunnels.
Other outcomes measured included improvements in the International Hidradenitis Suppurativa Severity Score System (IHS4), changes in lesion counts, flare rates, and the achievement of a minimal clinically important difference in the Dermatology Life Quality Index (DLQI).
Results were presented as odds ratios or mean differences accompanied by 95% confidence intervals.
At weeks 48–52, the analysis revealed that bimekizumab consistently offered higher odds of achieving a clinical response compared to secukinumab across all HiSCR thresholds and IHS4 outcomes.
Patients undergoing treatment with bimekizumab were also found to experience more significant improvements in their quality of life and encountered fewer disease flare-ups. Reductions in the counts of inflammatory nodules and draining tunnels were generally more favorable for bimekizumab as well.
When comparing with adalimumab, bimekizumab demonstrated a greater likelihood of achieving HiSCR50 and HiSCR75 responses, along with more pronounced reductions in both inflammatory nodule and draining tunnel counts.
However, differences at more stringent response thresholds, such as HiSCR90, were less pronounced and not consistently statistically significant, suggesting some overlap in higher-level responses between the treatments. Notably, bimekizumab maintained its efficacy even among biologic-experienced patients, who are typically more challenging to treat.
Bimekizumab operates by selectively inhibiting both IL-17A and IL-17F, cytokines that are implicated in the pathogenesis of HS. The findings from this MAIC indicate that this dual inhibition may provide more sustained disease control compared to targeting IL-17A or TNF-α alone. These observed improvements in lesion burden, flare reduction, and quality of life are particularly significant given the chronic and debilitating nature of HS.
Nonetheless, these results should be interpreted with caution due to several limitations. MAIC analyses that are unanchored rely on the premise that all relevant prognostic factors have been adequately matched, and any unmeasured differences between trial populations may introduce residual bias.
Furthermore, safety outcomes were not formally compared owing to the limited and heterogeneous nature of reporting across the studies.
This MAIC presents comparative evidence suggesting that bimekizumab may provide superior long-term efficacy compared to both secukinumab and adalimumab in adults dealing with moderate to severe HS. While the nature of the analysis is indirect, the utilization of patient-level data alongside established analytical methods offers valuable insights in the absence of head-to-head trials, thereby aiding informed decision-making in the evolving landscape of biologic treatments for HS.
