Content provided in partnership with
Pharma Industry
Industry: Email Alert RSS FeedRemittive effects of intramuscular alefacept in psoriasis
Journal of Drugs in Dermatology, Dec, 2003 by Kenneth B Gordon, Richard G Langley
Abstract
Alefacept is the first biologic agent approved for the treatment of chronic plaque psoriasis in the United States. Alefacept, administered intravenously (IV) or intramuscularly (IM), was found to be well tolerated, safe. and efficacious in two pivotal phase 3 studies in patients with moderate to severe psoriasis. Treatment with IV alefacept was associated with a median duration of off-treatment response of 216 days (approximately 7 months). In a follow-up extension study to the phase 3 IM study, duration of therapeutic response was also examined. Patients who achieved a [greater than or equal to] 75% reduction in baseline Psoriasis Arcs and Severity Index (PASt 75) with the first course of alefacept 15 mg IM in the phase 3 study maintained a PASI 50 for a median duration of 209 days. In addition, the extension study demonstrated that a second course of IM alefacept is safe and well tolerated in patients with psoriasis.
- Most Popular Articles in Health
- Fuel your workout: exercisers who eat before they work out have more energy ...
- Soothe a dry, itchy scalp: 5 easy expert solutions
- Cocktails and calories: Beer, wine and liquor calories can really add up. ...
- The sour truth about apple cider vinegar - evaluation of therapeutic use
- The, six best supplements you've never heard of: these secret weapons can ...
- More »
Introduction
Psoriasis is a chronic inflammatory skin disease that affects up to 2.5% of the world's population (1). It is characterized by the formation of scaly and inflammatory skin lesions that commonly fluctuate through periods of remissions and exacerbations. In the more severe form of psoriasis, the skin lesions can be itchy, painful, disabling, and disfiguring. Consequently, the burden of psoriasis is significant and is associated with considerable distress and reduced quality of life (2).
Treatments for psoriasis are either suppressive or remittive (3). With the use of suppressive agents, symptoms of the disease recur shortly after therapy is discontinued. Remittive therapies provide extended periods during which affected individuals maintain response even after therapy is stopped. Most conventional treatments for moderate to severe psoriasis, including cyclosporine, methotrexate, retinoids, and ultraviolet B (UVB) light therapy, are suppressive and require continuous treatment to control the disease. Psoralen with ultraviolet A (PUVA) is the only traditional therapy that has been shown to be remittive. In addition, safety and tolerability concerns with conventional therapies limit their chronic use (4). Intermittent or rotational therapies are often used to overcome these shortcomings, but patients frequently exhaust their conventional treatment options as a result of poor efficacy, safety concerns, or disease relapse. Consequently. there is a high unmet need for treatments that can provide safe and long-lasting off-treatment remission of psoriasis.
Advances in the understanding of the molecular basis of psoriasis have determined that the disease is primarily mediated by T-cells (5,6). This finding has been paralleled by the development of novel biologic agents (e.g., proteins synthesized using recombinant DNA technology m mimic naturally-occurring proteins) that target key pathogenic mechanisms underlying psoriasis (5). Alefacept is the first biologic agent to be approved in the United States for the treatment of chronic plaque psoriasis. It has a dual mechanism of action that interferes with T-cell activation and proliferation and also reduces the number of pathogenic memory T-cells (5,7). This reduction in memory T-cells has been shown to correlate with the clinical benefit and remittive effects of alefacept (8,9).
Alefacept, administered by an intravenous (IV) bolus injection or intramuscular (IM) injection, has been demonstrated to be safe and effective in phase 3 studies conducted in patients with moderate to severe chronic plaque psoriasis (10,11) In the phase 3 study of IV alefacept, the duration of off-treatment response in responders to a single course of alefacept was more than 7 months (10). Compared with a single course of IV alefacept, treatment with a second course was equally well tolerated and added incremental benefits by increasing the proportion of responders and prolonging the duration of response (10). This article describes the duration of response to a single course of IM alefacept based on the phase 3 study and its extension study. In addition, the efficacy and tolerability associated with two courses of IM alefacept are presented.
Methods
The methods for the phase 3 study of IM alefacept have been previously published (11). Briefly, patients with moderate to severe chronic plaque psoriasis were randomized to receive a single course of placebo, alefacept 10 mg, or alefacept 15 mg. A course was defined as 12 weeks of once-weekly injections followed by [greater than or equal to] 12 weeks of treatment-free follow up. The methods for the multicenter, double-blind extension are described in the following sections.
Study Population
To be eligible for entry into the extension study, patients must have received at least 8 doses of study drug in the phase 3 study of IM alefacept and must have completed all post-dosing visits in that study. Patients were required to enroll in the extension study within 14 days of completing the last visit (at week 12 post-treatment) of the phase 3 study. Any patient who initiated alternative systemic therapy, phototherapy, or disallowed therapy prior to week 8 in the phase 3 study, or who had enrolled in any other study of drug or non-drug therapy, was excluded from the extension study.
Find Research Guides for:
Most Popular Articles in Health
- Fuel your workout: exercisers who eat before they work out have more energy ...
- Soothe a dry, itchy scalp: 5 easy expert solutions
- Cocktails and calories: Beer, wine and liquor calories can really add up. ...
- The sour truth about apple cider vinegar - evaluation of therapeutic use
- The, six best supplements you've never heard of: these secret weapons can ...
- More »