A Randomized Controlled Study of Combination Therapy With Alefacept and Narrow Band UVB Phototherapy (UVB) for Moderate to Severe Psoriasis: Efficacy, Onset, and Duration of Response
August 2012 | Volume 11 | Issue 8 | Original Article | 929 | Copyright © August 2012
Harvey Lui MD FRCPC,a Wayne Gulliver MD FRCPC,b Jerry Tan MD FRCPC,c Chih-Ho Hong MD FRCPC,d Peter Hull MBBCh MMed (Derm) PhD FRCPC,e Neil H Shear MD FRCPC FACP,f Fran Paradiso-Hardy PharmD,g and Robert Bissonette MD MSc FRCPCh
aUniversity of British Columbia, Vancouver, Canada; bNewLab Clinical Research, St. John's, Canada cHealthy Image Center for Cosmetic Dermatology, Windsor, Canada; dGuildford Dermatology Associates, Surrey, Canada eDivision of Dermatology, University of Saskatchewan, Saskatoon, Canada; fUniversity of Toronto, Toronto, Canada gAstellas Pharma Canada Inc., Markham, Canada; hMedQualis Inc., Montreal, Canada
Abstract
Background: Alefacept is an effective intermittent treatment for psoriasis that can provide long-lasting remissions. Combination therapy with narrow-band ultraviolet B (nbUVB) phototherapy may enhance treatment outcomes and accelerate the onset of clinical response.
Objective: To assess the efficacy of alefacept in combination with nbUVB phototherapy compared to alefacept alone in subjects with moderate to severe psoriasis.
Methods: Ninety-eight adults with moderate to severe psoriasis were randomized to treatment with alefacept 15 mg intramuscularly (IM) once weekly for 12 weeks alone or in combination with three times weekly nbUVB treatments in this prospective, open-label, assessor-blinded, randomized, multicenter, parallel-group, 36-week study.
Results: A statistically significantly greater proportion of subjects in the alefacept plus nbUVB arm achieved the primary endpoint of PASI 75 at week 16 compared to subjects in the alefacept alone arm (44.9% vs 22.5%, P=0.032). Secondary outcomes were also in favor of the alefacept plus nbUVB group, including the proportion of subjects achieving a Physician Global Assessment (PGA) score of clear or almost clear at any time during the study (59.2% vs 34.7%, P=0.026) and reduction in percent body surface area (BSA) involved with psoriasis at week 16 (13.4% vs 8.0%, P<0.001). The onset of clinical response was significantly faster in the combination therapy group compared to monotherapy (mean time to PASI 75: 82 vs 107 days, P=0.007). Both treatments were generally well tolerated.
Limitations: Open-label, assessor-blinded study without a phototherapy-only treatment arm.
Conclusion: The addition of nbUVB to treatment with alefacept significantly enhanced and accelerated the clinical benefits of alefacept therapy and was generally safe and well-tolerated.
J Drugs Dermatol. 2012;11(8):929-937.
INTRODUCTION
Psoriasis is a T-lymphocyte (T-cell) mediated inflammatory
skin disorder with an estimated prevalence of 1% to 3%,1 with up to one-third of affected individuals exhibiting
moderate to severe disease.2 Psoriasis is known to have a substantial negative impact on patient well being and quality of life,3,4 including increased levels of unemployment and reduced income.5 Numerous therapies are available for the treatment of psoriasis, including topical therapies, phototherapy, systemic agents, and biologic therapies. Moderate to severe psoriasis generally requires more aggressive treatment, with guidelines recommending the use of phototherapy, systemic agents, or biologic therapy, with or without adjunctive topical agents.2,6
Alefacept was one of the first biologic therapies approved for the treatment of psoriasis. This dimeric recombinant fusion
protein combines the extracellular CD2-binding portion of lymphocyte function-associated antigen (LFA-3) and the Fc portion of human IgG1.7 Alefacept has a dual mechanism of action
that specifically targets memory-effector T-cells: it prevents activation of T-cells by blocking their interaction with antigen-presenting cells, and it induces apoptosis of previously activated T-cells, thereby reducing the population of activated memory T-cells in the circulation and in the skin.8,9 This latter effect is thought to be responsible for the prolonged and sustained remissions
demonstrated with alefacept (lasting a median of 7 months after one standard course of therapy),10 making intermittent
treatment possible.11 Clinical studies suggest that the maximal antipsoriatic effects of alefacept occur sometime after a standard 12-week course of therapy12; thus, there has been growing interest in the potential for combining this therapy
