Risk of Paradoxical Hidradenitis Suppurativa in Psoriasis Varies by Biologic Agent

The likelihood of treatment-induced hidradenitis suppurativa (HS) varied by more than twofold across different types of biologic therapies for psoriasis, an analysis of a large clinical database showed.

The tumor necrosis factor (TNF) inhibitor infliximab (Remicade) carried the highest relative risk (RR 2.08), followed by adalimumab (Humira). Secukinumab (Cosentyx) and ustekinumab (Stelara) had non-significant RRs exceeding 1.0. Guselkumab (Tremfya) and risankizumab (Skyrizi) had a significantly lower risk of paradoxical HS as compared with a propensity-matched control group.

The origin of biologic-induced HS remains unclear, but observations may provide insight into the “complex pathogenesis” of HS, wrote James Briley, DO, of Stony Brook University Hospital in New York, and colleagues in the Journal of Drugs in Dermatology.

“Unlike etanercept [Enbrel] and certolizumab pegol [Cimzia], adalimumab and infliximab are full monoclonal antibodies to TNF-α,” the authors noted. “The unmodified Fc region of these biologics can activate the complement cascade, increasing C5a and NLRP3 inflammasome levels, which simulate interleukin (IL)-1β, a key HS inflammatory marker. On the other hand, unlike IL-17 and IL-12/23 antagonists, IL-23 inhibitors may be protective of HS by avoiding stimulation of compensatory inflammatory markers.”

“Secukinumab and ixekizumab [Taltz] both inhibit IL-17A, but induction of a negative feedback loop in the IL-23/IL-17 axis can upregulate IL-23 and Th17, balancing out HS incidence,” they added. “Furthermore, although ustekinumab is also an IL-23 inhibitor, additional IL-12 downregulation may decrease IFN-γ levels, inducing additional stimulation of IL-1β and subsequent HS.”

Multiple studies have shown an association between psoriasis and HS, and reports of the conditions’ co-existence have become more frequent in recent years. One recent study provided evidence of shared genetic susceptibility for HS and psoriasis at non-HLA loci.

The reports have included several studies documenting “paradoxical hidradenitis suppurativa” in patients with psoriasis treated with biological agents. Limited data exist regarding the scope of the phenomenon and where HS risk varies among biologic therapies used to treat psoriasis. To address these issues, Briley and colleagues conducted a retrospective cohort study involving the TriNetX clinical database.

The analysis included patients with diagnoses of psoriasis or psoriasis vulgaris and one or more prescriptions for approved psoriatic biologic agents, excluding all other therapies. The analysis did not include certolizumab, brodalumab (Siliq), tildrakizumab (Ilumya), and bimekizumab (Bimzelx) because of low sample sizes.

Investigators compared HS rates in 72,000 patients treated with eight different biologics and a 72,000-patient propensity-matched control group with psoriasis/psoriasis vulgaris and no treatment with a biologic agent. Patients in the control group were numerically matched with the number of patients treated with each of the biologic therapies. The study excluded patients who had an HS diagnosis prior to their first prescription for a biologic agent.

The investigators identified 387 cases of treatment-related HS in the biologic group and 371 in the control group. Adalimumab (192 vs 136) and infliximab (51 vs 25) accounted for the difference in HS diagnoses. Number of HS diagnoses and number of patients treated were:

• Adalimumab (192/26,193) – RR 1.44 (95% CI 1.16-1.80, P<0.001)
• Infliximab (51/4,257) – RR 2.08 (95% CI 1.29-3.35, P=0.002)
• Etanercept (25/10,032) – RR 0.64 (95% CI 0.39-1.06)
• Secukinumab (32/6,666) – RR 1.12 (95% CI 0.68-1.85)
• Ixekizumab (15/4,474) – RR 0.58 (95% CI 0.31-1.09)
• Risankizumab (19/8,687) – RR 0.42 (95% CI 0.24-0.71, P<0.001)
• Guselkumab (≤10/3,987) – RR 0.36 (95% CI 0.17-0.73, P=0.003)
• Ustekinumab (43/7,015) – RR 1.03 (95% CI 0.67-1.57)

“Greater awareness of paradoxical HS onset is important during psoriasis treatment to discontinue treatment and alleviate symptoms,” the authors wrote of their findings. “Our data suggest that adalimumab and infliximab have higher occurrences of paradoxical HS during psoriasis treatment. Furthermore, physicians may consider risankizumab or guselkumab as alternative therapies should paradoxical symptoms occur.”