NEW ORLEANS – Adalimumab demonstrated significant efficacy for moderate to severe hidradenitis suppurativa in an interim 16-week analysis of a 52-week placebo-controlled randomized trial.
Dr. Alexa B. Kimball
"Overall I was really pleased with seeing these results in terms of moving the science forward and managing these patients. ...This is a disease that I think has really been underappreciated and under-managed and underresearched," Dr. Alexa B. Kimball said in presenting the interim phase II study findings at the annual meeting of the American Academy of Dermatology.
Anti–tumor necrosis factor (TNF) therapy is of considerable research interest because of the disease’s prominent inflammatory component and the shortcomings of current therapies, explained Dr. Kimball of Harvard Medical School, Boston.
The clinical trial involved 154 patients with moderate to severe hidradenitis suppurativa who were randomized to 16 weeks of double-blind adalimumab (Humira) at 40 mg per week, 40 mg every other week, or to placebo. After 16 weeks, everyone was placed on 36 weeks of open-label adalimumab at 40 mg every other week, the standard psoriasis dosing. The loading dose was 80 mg at week 0 in the every-other-week group and 160 mg at week 0 and 80 mg at week 2 in the weekly therapy arm.
Because no practical instrument existed for grading the severity of hidradenitis suppurativa and scoring change over time, Dr. Kimball and her coinvestigators created one: the Hidradenitis Suppurativa Physician Global Assessment (HS-PGA).
At baseline, two-thirds of participants had moderate disease as defined by the HS-PGA. Another 20% had very severe disease, with more than five abscesses or draining fistulas. The rest had severe disease.
At 16 weeks, 49% of patients on weekly adalimumab had improved to clear, mild, or minimal disease status. This was a significantly better result than the 21% rate in patients on alternate-week adalimumab or the 24% on placebo.
The primary study end point required achieving an HS-PGA score of clear, minimal, or mild plus at least a two-grade improvement. However, the 20% of subjects with baseline very severe disease could only reach the primary end point by improving at least three grades to mild disease, and this proved a very high bar for the very severely affected subgroup, who often have scarring and tracts that are irreversible. Nonetheless, 18% of patients on weekly adalimumab achieved the primary end point, a significantly higher proportion than the 10% on every-other-week anti-TNF therapy or the 4% on placebo, Dr. Kimball noted.
Skin pain was a prominent feature among study participants. Their mean baseline pain score was roughly 55 points on a 0-100 visual analog scale. At week 16, however, 48% of patients in the weekly adalimumab arm had a 30% or greater reduction in pain score, compared with baseline, which is widely accepted in pain studies as a clinically meaningful improvement. This was a significantly higher proportion than the 36% rate among patients on alternate-week adalimumab or the 27% rate among controls.
Treatment-emergent side effects were what dermatologists have come to expect with anti-TNF therapy for psoriasis. Serious adverse events occurred in two patients in the placebo arm, three on alternate-week adalimumab, and four on weekly therapy with the biologic agent.
Dr. Kimball said she suspects that minor skin infections, which were fairly common in the first 16 weeks of the study, will become less of an issue with longer-term adalimumab therapy, as inflammation diminishes and the substantial baseline microbiologic load decreases. In the future, she added, it might be useful to prescribe antibiotics during the first 12-16 weeks of adalimumab therapy while waiting for the TNF inhibitor to help patients gain good control of the disease.
She noted that the hidradenitis suppurativa population in this study differed in several key respects from the psoriasis patients for whom dermatologists are accustomed to prescribing anti-TNF biologics. Seventy percent of participants in the hidradenitis suppurativa study were women, and the mean body weight across the three study arms was 95-100 kg. In contrast, typically two-thirds of participants in studies of anti-TNF therapy for psoriasis are men, with a mean weight of 85-90 kg.
Effective new therapy for hidradenitis suppurativa is sorely needed because affected patients often end up undergoing surgery, which entails removing large areas of skin and a 4- to 6-month recovery. "While surgery does result in significant improvements in quality of life overall, it’s a really long haul and incredibly disfiguring," the dermatologist observed.
Dr. Kimball declared that she serves as an investigator for and consultant to Abbott Laboratories, which is sponsoring the phase II trial, and in similar capacities with other pharmaceutical companies.