TNF Inhibitors Prove Effective

MauiDerm 2015 - Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory disease that has historically been very challenging to treat, with truly effective therapeutic modalities few and far between. Recent research with TNF inhibitors has shown promise for the treatment and management of HS, offering effective systemic therapy for moderate to severe cases.

Also known as acne inversa, HS is characterized by the development of painful abscesses, nodules, and fistulas in apocrine gland-bearing skin such as in the inguinal, sub-mammary, and axillary regions.  Keloids, contractures, and immobility commonly develop in the affected areas. In severe cases, HS can be associated with a number of co-morbidities including metabolic syndrome, follicular occlusion disorders, spondylarthropathy, inflammatory bowel diseases such as Crohn’s disease, and others. HS and its co-morbidities can have a significant negative impact on patients’ quality of life, begging the need for effective therapies that can address this notoriously difficult-to-treat disease.

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“It is very important to remember that HS is an inflammatory disease akin to psoriasis, psoriatic arthritis, and Crohn’s disease. As such, evolving agents such as the TNF inhibitors that can reduce the inflammation in the patient could be an ideal treatment option for HS patients, particularly those with moderate to severe disease or in refractory cases,” said Bruce E. Strober, M.D., Ph.D., associate professor and vice chair, department of dermatology, University of Connecticut School of Medicine, Farmington, Conn.

According to Dr. Strober, several different TNF inhibiting agents have been tried and researched in clinical trials for the treatment and improvement of the symptoms of HS including etanercept (Enbrel, Amgen), infliximab (Remicade, Janssen), and most recently adalimumab (Humira, AbbVie).

AbbVie recently announced phase 3 data of the PIONEER I study, a 36-week, multicenter, randomized, double-blinded, two-period clinical trial that evaluated the efficacy and safety of adalimumab in 307 patients with moderate to severe HS¹. In the first 12-week study period (Period A), patients were randomized to receive adalimumab 160mg at week 0, 80mg at week 2 and 40mg once weekly (n=153) starting at week 4, or placebo (n=154). Following Period A, eligible patients were re-randomized in a 24-week treatment period (Period B) in which they received adalimumab 40mg weekly, 40mg every other week, or placebo. The results of Period B have not yet been released. Using the Hidradenitis Suppurativa Clinical Response (HiSCR) measure, investigators assessed treatment response, which was defined as at least 50% reduction from baseline in total abscess and inflammatory nodule count at week 12 with no increase for either abscess or draining fistula count.

NEXT: Results from period A

The results from Period A were very positive, with those patients who received adalimumab 40mg weekly showing significant improvement in their HS related abscesses and inflammatory nodules compared to those in the placebo arm at week 12 (41.8% vs 26%, respectively). Less than 5% of all patients experienced adverse events in this study: the most common were exacerbation of HS (9.2% vs 13.2%), nasopharyngitis (5.9% vs 10.5%), and headache (9.2% vs 9.9%).

“One of the central goals of HS therapy is to reduce the inflammatory response. The nice thing about the implementation of systemic therapies like adalimumab is that we can treat the disease on a whole and not just the symptoms. TNF inhibitors can effectively address the inflammatory component and can potentially maintain a long-term improvement and relief in patients’ HS related symptoms,” said Neal Bhatia, M.D., Director of Clinical Dermatology, Therapeutics Clinical Research in San Diego, Calif.

For milder cases of HS, Dr. Strober said that patients can be treated successfully with topical agents such as clindamycin and benzoyl peroxide. For moderate cases, the addition of oral antibiotics of the tetracycline class (doxycycline or minocycline) would be the next therapeutic step Dr. Strober said, or even the use of oral clindamycin in combination with rifampin.

“In truth however, there are very few good therapies for moderate to severe HS until we talk about the TNF inhibitors. Adalimumab and infliximab are two drugs that have shown a very good efficacy in moderate to severe HS and in my opinion, TNF inhibition will be the gold standard therapy for HS, particularly in more severe and refractory cases,” Dr. Strober said.

According to Dr. Strober, both adalimumab and infliximab have been shown to work well in over half the patients who take it and can benefit from those drugs. In addition to TNF inhibition, Dr. Strober recommends that patients concomitantly take methotrexate because it augments response by raising drug levels and reduces immunogenicity of the biologic.

“I think physicians should not shy away from more aggressive therapy in HS patients because their quality of life without treatment is miserable. These patients are suffering and this is not a condition where we want to be timid and hold back because of the concern of side effects such as nasopharyngitis or headaches, which in the big picture are truly minimal compared to the devastating consequences of HS disease when not treated effectively,” Dr. Bhatia said.

NEXT: References

Disclosures:

Dr. Bhatia has no relevant disclosures.

Dr. Strober is an Advisory Board member and consultant at AbbVie and receives an honoraria from AbbVie.

References:

1.     Clinical research, clinical trials and therapeutics. J Invest Dermatol. 2014;134 Suppl 2:S30-8.