Meta-regression reframes efficacy, elevating adalimumab and bimekizumab while narrowing secukinumab’s edge in advanced disease.
Baseline draining tunnel burden independently predicts biologic response in hidradenitis suppurativa and materially alters comparative efficacy estimates, according to Australian researchers.
In a network meta-analysis with meta-regression of phase 3 trials, adjustment for tunnel count preserved statistically significant benefit for adalimumab and bimekizumab but rendered secukinumab non-significant versus placebo in patients with more advanced disease, they found.
Results have been published in the Australasian Journal of Dermatology.
“Hidradenitis suppurativa is a challenging, heterogeneous inflammatory skin disease, with three approved biologic therapies,” the researchers wrote.
“No head-to-head studies exist comparing these therapeutic modalities, and previous work has identified the influence of baseline disease severity upon clinical response.
“We aimed to perform a network meta-analysis of approved biologic therapies and meta-regression of baseline disease severity in moderate to severe HS.”
Drawing on six randomised controlled trials across adalimumab, bimekizumab and secukinumab, the analysis initially confirms familiar territory: adalimumab leads for HiSCR50 response at week 16 (OR 2.81), followed by bimekizumab at both dosing schedules, with secukinumab trailing but still outperforming placebo.
Once baseline disease characteristics were interrogated, only one factor consistently moved the needle – draining tunnel count.
Each incremental increase in tunnel burden significantly reduced the odds of achieving clinical response (OR 0.23), establishing tunnels as the dominant effect modifier across studies.
Adjusting for this variable changed the picture. Adalimumab and bimekizumab not only retained significance but demonstrated stronger adjusted odds of response, suggesting resilience in more advanced disease.
In contrast, both secukinumab regimens lost statistical significance versus placebo after adjustment, with credible intervals crossing one.
“Rather than suggesting a lack of efficacy of secukinumab in HS overall, it instead suggests that the odds of achieving HiSCR-50 are reduced with every unit increase in baseline tunnel count, and above a certain threshold (3 in our weighted analysis) may not meet significance over placebo,” the researchers wrote.
“Therefore, secukinumab may be of more benefit in individuals with lower baseline tunnel counts, while alternative agents such as bimekizumab and adalimumab may have clinically meaningful activity in such cases.
This reframing addresses a longstanding gap in hidradenitis suppurativa evidence synthesis.
Previous network meta-analyses have largely treated trial populations as interchangeable, despite clear heterogeneity in disease severity. By incorporating meta-regression, the current study aligns comparative efficacy more closely with clinical reality.
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“Network meta-analysis of efficacy of approved therapies in hidradenitis suppurativa identifies adalimumab 40mg weekly as the most efficacious therapy over placebo in moderate to severe HS, followed by bimekizumab q2weekly, bimekizumab q4weekly, secukinumab q2weekly and secukinumab q4weekly,” the researchers concluded.
“Baseline tunnel count was a significant a priori covariate influencing the odds of clinical response as measured by HiSCR50 compared to placebo.
“Meta-regression and adjusted odds ratios accounting for baseline draining tunnels resulted in an increase in the odds of clinical response for adalimumab 40 mg weekly, bimekizumab q2weekly and bimekizumab q4weekly, and a reduction in the odds of clinical response for both secukinumab doses.”
Accounting for baseline disease severity, particularly draining tunnel burden, was critical for interpreting treatment efficacy and matching therapies to the right patient populations, as it directly influenced response rates, the researchers noted.
Incorporating tunnel count as a stratification factor in future RCTs would improve balance between study arms, reduce confounding, and allow more accurate, clinically meaningful comparisons of therapeutic effect sizes in hidradenitis, they said.
