An open-label pilot study of alefacept for the treatment of pyoderma gangrenosum.

BACKGROUND

Pyoderma gangrenosum (PG) is a chronic inflammatory disease that causes painful cutaneous ulcers that are difficult to treat. Currently, systemic immunosuppressants, often including prednisone, are the mainstay of therapy. Long-term therapy with these agents is often required which exposes patients to possible adverse effects. An alternative treatment that is safe and effective is truly needed.

OBJECTIVE

To study the efficacy and safety of alefacept, which inhibits T-cell activation and selectively reduces the T-cell population, for treatment of PG.

METHOD

In this prospective open-label pilot study, four patients diagnosed with PG received weekly doses of 15 mg alefacept intramuscularly for 20 weeks with 12-week treatment-free follow-up. The primary efficacy end point was the proportion of patients achieving remission as defined by a Physician Global Assessment (PGA) of 'clear' or 'almost clear.' Secondary endpoints included proportion of patients achieving 50% improvement in PG lesion size (measured in mm) and proportion of patients achieving resolution of inflammation (an erythema score of 0 and a border thickness of 0 on scales of 0-4).

RESULTS

By week 20, one (25%) of the four patients achieved remission, two showed marked improvement in severity on PGA, and one had slight improvement. One patient showed a 98% decrease in lesion size; two other patients evidenced a decrease in the number of small lesions as well as improvements in primary lesion sizes, but did not surpass the 50% criterion. All four patients showed improved erythema scores during treatment, though only one patient showed a complete resolution of inflammation.

LIMITATIONS

It may be difficult to generalize the results of this study to a larger population of patients with PG due to the small sample size and lack of a control group. A longer treatment interval might have been required. Safety and efficacy of long-term therapy is unknown.

CONCLUSION

In this pilot study it appears that alefacept treatment may significantly reduce PG severity levels as evidenced by improvement in PGA, Subject Global Assessment, and inflammation scores in all patients. Alefacept may be a safe and effective alternative to current systemic immunosuppressants used to treat PG. Double-blinded, controlled trials are necessary to further evaluate the safety and effectiveness of this treatment.