PRAGUE – A handful of drugs are backed by solid-quality evidence for the treatment of hidradenitis suppurativa, although to date no form of therapy is approved for this indication.
Topping the list are the tumor necrosis factor (TNF)-alpha inhibitors. They have a plausible mechanism of benefit in hidradenitis suppurativa (HS). They’ve also demonstrated effectiveness for this common inflammatory skin disease in randomized, placebo-controlled clinical trials, Dr. Gregor B. Jemec said at the annual congress of the European Academy of Dermatology and Venereology.
Dr. Gregor B. Jemec
In addition, one older randomized trial suggests that topical clindamycin is effective, mainly in milder cases. The most promising antibiotic regimen, consisting of oral clindamycin at 300 mg twice daily plus rifampicin at 600 mg daily, has not been studied in a randomized trial. But several large, rigorous case series have demonstrated "dramatic improvement" in response to the combination, according to Dr. Jemec of the University of Copenhagen.
TNF Inhibitors
The discovery that anti-TNF therapy is effective for HS was a serendipitous finding that occurred when physicians noted marked improvement in the skin disease in a patient taking infliximab for Crohn’s disease. The biologic plausibility of the observed benefit is underscored by the fact that TNF levels are actually more elevated in patients with HS than in those with psoriasis, Dr. Jemec said.
Infliximab missed its primary efficacy end point of clear or almost clear in a 38-patient randomized trial, but it did hit several clinically important secondary end points, including pain reduction and improved quality of life (J. Am. Acad. Dermatol. 2010;62:205-17).
On the other hand, etanercept showed no benefit in a 20-patient pilot randomized trial (Arch. Dermatol. 2010;146:501-4).
By far the best studied TNF inhibitor in HS is adalimumab (Humira). It is the subject of two ongoing, pivotal phase III randomized, double-blind, placebo-controlled, multinational clinical trials aimed at winning adalimumab regulatory approval as the first-ever drug indicated for the treatment of HS.
Last year, Dr. Alexa B. Kimball of Harvard Medical School, Boston, presented the primary end point of a 16-week, randomized, double-blind phase II clinical trial involving 154 patients with HS who were placed on adalimumab 40 mg weekly, adalimumab 40 mg every other week, or placebo. At week 16, a Physician Global Assessment of clear, minimal, or mild disease with at least a 2-grade improvement over baseline was documented in 23.5% of patients on placebo, 21.2% of those on alternate-week adalimumab, and 49% of those on adalimumab 40 mg every week.
With a therapy that achieves clear or close to it in only half of treated patients, other end points take on added importance. At this year’s EADV (European Academy of Dermatology and Venereology) congress, Dr. Kimball and others presented several key secondary outcomes from the phase II study. One involved pain, a particularly prominent feature in HS. From a mean baseline pain score of 52 on a 0-100 visual analog scale, the weekly adalimumab group’s score dropped by a placebo-subtracted 15.8 points by week 2, 18.4 points at week 4, 11.7 points by week 8, 20.7 points at week 12, and by 11 points at week 20.
The minimum clinically important difference, predefined as at least a 15.4-point improvement in self-rated pain scores, occurred in 33% of the weekly adalimumab group, compared with 15% of patients on placebo at week 2. By week 12 this end point had been achieved in 63% of the weekly adalimumab group and 26% of the placebo group. Adalimumab every other week didn’t consistently improve pain relative to placebo, she reported.
Dr. Ulrich Mrowietz reported separately that the impaired work productivity that often affects patients with HS was significantly lessened by treatment with adalimumab 40 mg weekly. Total work productivity impairment as measured at week 16 by the Work Productivity and Activity Impairment Questionnaire improved by a mean of 15 points in the weekly adalimumab group while worsening by 2.7 points with placebo; the net 17.7-unit difference exceeded the minimum clinically important difference threshold of 16.2 points.
Patients assigned to weekly adalimumab also experienced significantly improved scores on the Dermatology Life Quality Index beginning on week 2 and lasting throughout the 16-week study. At week 16, for example, they enjoyed a mean 5.5-point improvement relative to baseline, compared with a 1.6-point improvement with placebo, according to Dr. Mrowietz of University Medical Center in Kiel, Germany.
Oral Antibiotics
Dr. Jemec highlighted as particularly impressive a retrospective French case series of 116 patients with severe HS treated using the combination of clindamycin 300 mg twice daily and rifampicin 600 mg daily. Severity scores decreased as a result by 50%. Seven percent of patients dropped the therapy due to diarrhea (Dermatology 2009;219:148-54).