Effectively managing GIF in the psoriasis patient

Efalizumab is an effective treatment that gives long-term safety and efficacy for the psoriasis patient population. Efalizumab is a recombinant, humanized, monoclonal IgG antibody that inhibits multiple T-cell mediated events including T-cell activation, T-cell trafficking to sites of cutaneous inflammation, and T-cell reactivation in the skin.

Psoriasis can manifest as a stable disease but will often wax and wane over time. Generalized inflammatory flare (GIF), also known as general inflammatory exacerbation, involves a widespread worsening of psoriasis with an inflammatory component, and is a rare event, occurring in 1 percent to 3 percent of patients treated with efalizumab.

GIF manifestation

GIF typically manifests during the first six to 10 weeks of treatment, and affects existing plaques with or without the presence of new lesions.

In a recent case study presented at the American Academy of Dermatology Summer 2006 meeting, six patients experiencing GIF were examined, all of whom were treated successfully with a short course of a concomitant medication, returned to efalizumab monotherapy and maintained psoriasis clearance with follow-up.

Four of the six patients were treated with methotrexate, antibiotics and/or topical steroids, and the GIF events resolved within three to six weeks. A fifth patient could not tolerate high doses of methotrexate and was initially treated with a smaller dose of methotrexate for two months with little response; he switched to acitretin and responded within six weeks. The sixth patient was treated with acitretin and topical calcipotriene, and her GIF resolved after six weeks.

All six patients were treated through psoriasis exacerbations with courses of concomitant medications and were able to eventually continue with efalizumab monotherapy.

Safety data

While the safety data on concomitant therapies for psoriasis, with the exception of topical agents, have not been tested, a randomized phase 2 clinical trial demonstrated that efalizumab in combination with methotrexate was safe in treating psoriasis patients up to 24 weeks.

In the majority of cases, the flare will resolve, and the patient can continue with efalizumab monotherapy.

In the rare case where flare does not resolve, efalizumab should be discontinued and the patient should maintain systemic therapy. Efalizumab has demonstrated long-term safety, efficacy and health-related quality of life benefits in more than 3,500 patients through 15 clinical trials. Should a patient need to discontinue therapy for any reason, the efficacy of retreatment appears to be similar to that achieved during an initial course of efalizumab.

As the body of knowledge regarding efalizumab treatment expands, we now understand that the most effective way to address GIF is to continue on efalizumab therapy and initiate a concomitant four to six week course of a systemic therapy (usually methotrexate or cyclosporine). Most commonly used systemic agents are methotrexate and cyclosporine, although there are some reports of rapid improvement in GIF using oral prednisone or intramuscular Kenalog (Bristol-Myers Squibb).

If this strategy is ineffective, it may warrant transitioning this patient off efalizumab and onto another suitable therapy for psoriasis.

Dr. Turner is a clinical professor at the University of Tennessee, Division of Dermatology, Department of Medicine, Memphis, Tenn. He has been in private practice for the past 26 years.

Carey W, Glazer S, Gottlieb A, Lebwohl M, Leonardi C, Menter A, Papp K, Rundle AC, Toth D. Relapse, rebound, and psoriasis adverse events: An advisory group report. Journal of the American Academy of Dermatology, 2006;54(4 suppl 1): S171-181;

Menter A, Leonardi C, Sterry W, Bos J, Papp K. Long-term management of plaque psoriasis with continuous efalizumab therapy. Journal of the American Academy of Dermatology, 2006;54(4 suppl 1): S182-188;

Turner J, Crowley J, Shapiro S. Treatment through intercurrent generalized inflammatory flare during efalizumab therapy. Presented at: 2006 Summer Academy, American Academy of Dermatology;