BACKGROUND: The safety of biologic agents for psoriasis treatment is of particular importance in patient groups at higher risk for adverse events. We assessed the safety and efficacy of alefacept in elderly, obese, and diabetic patients with moderate to severe chronic plaque psoriasis by integrating data from phase 2 and 3 clinical studies and their extensions. OBSERVATIONS: Ninety-nine elderly, 652 obese, and 122 diabetic patients received at least 1 course of alefacept. In each cohort, accidental injury, headache, and pharyngitis were among the most common adverse events; infections were primarily common colds; and malignancies were mostly skin carcinomas. No opportunistic infections were reported. Safety was maintained over repeated courses. The safety profile of alefacept in each cohort was consistent with that of the overall population; however, additional data are needed to confirm our findings in the elderly and diabetic subgroups in the later courses due to the limited sample sizes. In course 1, 24% to 33% of patients achieved 75% or greater improvement in Psoriasis Area and Severity Index (PASI) at any time, with further enhancement of benefit with subsequent courses (eg, course 3, 41% to 58%). CONCLUSIONS: Alefacept was well-tolerated and effective in elderly, obese, and diabetic patients with psoriasis.