PARIS — More than three fourths of patients with longstanding hidradenitis suppurativa (HS) responded to treatment with the anti-IL-17 agent secukinumab (Cosentyx), according to small study reported here.
All but four of 18 patients met the Hidradenitis Suppurativa Clinical Response (HiSCR) criteria after 24 weeks of treatment with either of two doses of the interleukin-17 inhibitor. As a whole, the study population had a statistically significant decrease in the Sartorius Scale of disease activity and improvement in dermatology-specific quality of life, according to a presentation at the European Academy of Dermatology and Venereology meeting.
“Secukinumab appears to be promising for hidradenitis suppurativa, even for patients with prior anti-TNF (tumor necrosis factor) failure,” said David Rosmarin, MD, of Tufts Medical Center in Boston. “We observed rapid response, and the drug was well tolerated at both doses.”
“We need to prove the efficacy with a randomized, controlled trial,” he added. “We also have yet to define the optimal dose. Should patients receive induction therapy followed by maintenance? Do patients require weekly treatment, as has been used with adalimumab (Humira)?”
HS is an inflammatory condition characterized by abscess, nodules, sinus tract lesions, and ultimately, severe scarring. Affecting 1%-4% of the U.S. population, the condition occurs more often in women than in men and has associations with higher body mass index (BMI) and smoking. The condition causes significant quality-of-life impairment, Rosmarin noted in his introduction to the study.
As compared with normal skin, HS lesions have an increased Th17/Treg ratio, associated with elevated serum IL-17 and elevated concentrations of IL-17 cells in lesions, which can be corrected with anti-TNF therapy.
Secukinumab selectively binds IL-17A and has approved indications for psoriasis, psoriatic arthritis, and ankylosing spondylitis. Several case reports documented successful treatment of HS with secukinumab, using psoriasis dosing of 300 mg weekly for 5 weeks followed by maintenance every 4 weeks, Rosmarin noted.
The anti-IL-17 antibody was evaluated in a 28-week open-label study involving patients with moderate-to-severe HS. Investigators randomized patients to one of two dosing regimens: all patients received 5 weeks of induction, followed by maintenance therapy every 2 or 4 weeks thereafter to week 24.
The trial had a primary endpoint of HiSCR response, defined as no increase in draining fistula or abscess counts plus at least a 50% reduction in total inflammatory nodules (abscess and inflammation). Secondary endpoints included the mean change in Sartorius Scale and mean change in the Dermatology Life Quality Index (DLQI).
The 18 patients enrolled in the trial had a mean age of 33, even distribution of men and women, and mean disease duration of 12 years. On average, the patients weighed 227 pounds, and 61% of the study participants were current or former smokers. Rosmarin said 78% of the patients had Hurley Stage II HS, they had a mean Sartorius score of 166, mean DLQI of 12, and a third had not responded to prior anti-TNF therapy.
Results showed that 16 of the 18 patients completed at least 12 weeks of treatment, and 10 patients completed the trial. One patient stopped treatment early at week 4 because of a requirement for antifungal therapy, one at week 16 for HS surgery, and one at week 20 because of anemia. Two other patients were lost to follow-up at weeks 12 and 16.
Rosmarin reported that 14 of the 18 patients (78%) met the criteria for HiSCR response at last recorded observation, seven in each dosing group. Responders included five of six patients whose disease previously had not responded to anti-TNF therapy. Time to HiSCR response averaged 7 weeks, and eight patients achieved HiSCR response during the loading-dose phase.
The mean Sartorius score decreased by 28% (P=0.008), and the mean DLQI decreased (improved) by 3.6 points or 26% (P=0.04). Nine patients had DLQI improvement ≥5 points.
Overall, the treatment was well tolerated, and no patient stopped treatment because of adverse events, said Rosmarin. The most commonly reported adverse events were upper respiratory infection (seven patients), diarrhea (six), and Candida infection (four, all in the Q2W dosing group). No patient developed inflammatory bowel disease, which has been reported recently in some patients treated with secukinumab.
Future investigations of secukinumab in HS should examine more closely the risk of IBD, the impact of treatment on comorbidities and cardiovascular risk, and characteristics of patients who are likely to respond to the antibody, Rosmarin said in conclusion.
Rosmarin disclosed relationships with AbbVie, Dermavant, Lilly, Novartis, Janssen, Regeneron, Sanofi, Pfizer, and Celgene.