COMMENTARY

Biologic Therapy for Hidradenitis Suppurativa

Graeme M. Lipper, MD

Disclosures

March 23, 2010

Infliximab Therapy for Patients With Moderate to Severe Hidradenitis Suppurativa: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial

Grant A, Gonzalez T, Montgomery MO, Cardenas V, Kerdel FA
J Am Acad Dermatol. 2010;62:205-217

Background

Hidradenitis suppurativa (HS) is a chronic, debilitating disorder of the apocrine glands, characterized by recurrent inflammation, abscess and sinus tract formation, and progressive scarring, most commonly affecting intertriginous areas such as the inguinal folds, anogenital region, and axillae. Even mild HS can be painful and distressing, but moderate-to-severe disease is disfiguring and debilitating.[1] Traditional medical therapies including antibiotics (topical or oral), corticosteroids (intralesional or systemic), and oral retinoids offer only temporary improvement at best,[2] and surgical "cures" such as block excision with grafting to remove diseased tissue are painful and only variably effective.[3] Although the pathogenesis of HS remains unclear, recent data suggest that cytokine tumor necrosis factor alpha (TNF-alpha) may be a key mediator of inflammation in active disease. Furthermore, anecdotal reports and small case series support the notion that biologic agents that block TNF-alpha (infliximab, etanercept, adalimumab) may suppress HS, at least temporarily.[4,5,6] But are selective immunosuppressive drugs such as infliximab both safe and effective for the treatment of HS?

Study Summary

In the first placebo-controlled trial to address this important question, Grant and colleagues enrolled 38 otherwise healthy patients (26 women; ages 16-61 years) with moderate-to-severe HS and randomly assigned them to receive either infliximab (5 mg/kg, infusions given at weeks 0, 2, and 6) or placebo, for an 8-week initial treatment phase. In the second phase, patients assigned to infliximab (IFX) continued to receive infusions through week 22, and patients who initially received placebo were offered the opportunity to cross over and receive induction followed by maintenance IFX therapy. In the study's final, observational phase (weeks 22 through 52), patients were observed for time to relapse and adverse events.

The investigators assessed study participants at multiple timepoints using a trial-defined objective measure of HS severity (the HS severity index, or HSSI). In addition, secondary outcome measures included a physician's global assessment (PGA) score (higher score = worse symptoms), dermatology life-quality index (DLQI) score (higher score = more severe impairment), visual analog scale score (higher score = worse symptoms), and measurements of serum inflammatory markers (erythrocyte sedimentation rate, C-reactive protein). All study participants met standard criteria for infliximab therapy (eg, negative PPD, normal chest x-ray, negative hepatitis and HIV serologies, no history of lymphoproliferative malignancy, etc.)

By all outcome measures, IFX-treated patients with HS showed improvement compared with placebo controls. Specifically:

  1. By week 8 (end of double-blind phase), patients in the IFX group showed a significantly greater reduction in HSSI scores vs placebo controls. More patients receiving IFX showed an HSSI score reduction of between 25% and 50% than their placebo-matched controls (60% vs 5.6%, respectively).

  2. Most patients treated with placebo (88.9%) had less than a 25% reduction in HSSI score.

  3. After 8 weeks of treatment, mean PGA scores were lower for IFX-treated patients (1.8) vs placebo-treated controls (4.7).

  4. By week 8, patients receiving IFX enjoyed a mean improvement in DLQI score of 10 points; in contrast, patients receiving placebo showed a mean DLQI score improvement of only 1.6 points.

  5. During the crossover phase of the trial, patients switching from placebo to IFX showed similar improvement, reflected in all outcome measures.

  6. IFX treatment was associated with a significant drop in serum inflammatory markers (ESR and CRP).

  7. Treatments were well tolerated, with only 1 patient dropping out because of an infusion reaction.

  8. Meaningful follow-up (weeks 22-52) was limited as a result of high patient dropout during the observational phase of the study (not adverse-event related).

Viewpoint

HS is a frequently debilitating disorder with poor treatment options. In this context, Grant and colleagues offer promising data suggesting that infliximab infusions may, at a minimum, help to curb the symptoms of moderate-to-severe HS. Although only 1 patient experienced a significant treatment-related adverse event (infusion reaction), the small study size precludes any conclusions about treatment safety. As one point of concern, TNF-alpha-blocking drugs such as infliximab can increase the risk for severe or disseminated infection because patients with HS frequently develop secondary bacterial infections (eg, Staphylococcus aureus colonization, abscesses, and/or cellulitis). Such individuals should be followed closely for signs of worsening infection while on immunosuppressive drugs such as IFX. IFX should probably not be given in the perioperative period when surgical intervention (eg, block tissue excision, grafting) is planned. Finally, because of high patient dropout rates during their observational follow-up period, the investigators could not determine whether the observed clinical improvements were transient or long-lasting. Future studies should assess whether chronic suppressive therapy is necessary, and if so, at what optimal interval "booster" treatments should be given.

Abstract

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