|
Registration benefits include:
|
|
Access to CME/CE programs and certification
|
|
|
Free subscription to Biologic Bulletin newsletter
|
|
|
Reminders of new CME/CE activities
|
 REGISTER NOW
|
|
This Web site is supported by an
unrestricted educational grant from
Genentech, Inc.
|
|
|
|
 |
| Meetings/Links : Meeting Reports : Psoriasis and Biologic Therapy |
Update on the Efficacy of Biologic Agents in Psoriasis
Etanercept
A study by Dr. Gottlieb et al analyzed the effect of etanercept on skin and joint disease in 1,122 patients with psoriatic arthritis from 140 dermatology clinics.9 Patients received 25 mg etanercept twice weekly for 24 weeks. More than 75% of patients achieved a Physician's Global Assessment (PGA) of mild or better at week 25. It should be noted that PGA assessments are defined in terms of clear or almost clear, and it is not certain how the terms used by these investigators compare to the usual definitions of PGA. These patients also showed good response for their psoriatic arthritis. Of note was the fact that patients had a mean duration of psoriasis of 19 years and a mean duration of psoriatic arthritis of 7.21 years. The fact that psoriasis appeared, on average, about 11 years before psoriatic arthritis further substantiates the need for community dermatologists to be vigilant for the onset of psoriatic arthritis.
Infliximab
Infliximab is a chimeric (approximately 30% murine, 70% human) monoclonal antibody that binds to both soluble and membrane-bound TNF-a. Infliximab may also cause apoptosis of cells expressing transmembrane TNF-a. It is not yet approved for the treatment of psoriasis.
Antoni et al reported on two multicenter, randomized, placebo-controlled studies (IMPACT and IMPACT 2) of the efficacy of infliximab in psoriatic arthritis patients who also had psoriasis.10 In the IMPACT study, patients received either infliximab 5 mg/kg at weeks 0, 2, 6, 14, 22, 30, 38, and 48, or placebo through week 14 and infliximab thereafter (weeks 16, 18, 22, 30, 38, and 48). In the IMPACT 2 study, patients received either infliximab 5 mg/kg or placebo, at weeks 0, 2, and 6, and then every 8 weeks through week 22. In the IMPACT study, 59% of infliximab-treated patients achieved PASI 75 at week 50; in the IMPACT 2 study, 60% of infliximab-treated patients achieved a PASI 75 at week 24 (Figure 5). It is important to note that the patients in the IMPACT study had less psoriasis on study entry than did the patients in the IMPACT 2 study.
Figure 5. Infliximab: PASI 75 response in psoriatic arthritis patients.10
Adalimumab
Adalimumab is a fully human monoclonal antibody with a high affinity for both soluble and membrane-bound TNF-a. In the presence of complement, adalimumab can cause the lysis of cells expressing TNF-a on their surface. Adalimumab is not yet approved for the treatment of psoriasis.
Three posters reviewed the efficacy of adalimumab.11-13 Langley et al evaluated the efficacy of adalimumab in a 48-week extension trial.11 The lead-in study was a double-blind placebo-controlled 12-week study. Patients received either placebo (n=52), adalimumab 80 mg at week 0 followed by 40 mg every other week (EOW) starting at week 1 (n=45), or adalimumab 80 mg at week 0 and 1 followed by 40 mg/wk starting at week 2 (n=50). Patients on adalimumab 40 mg/wk were then continued in a double-blind fashion for an additional 12 weeks (n=47). Patients receiving adalimumab 40 mg/EOW were continued for an additional 12 weeks at that dose (n=43), and placebo patients were given adalimumab 80 mg at week 0 and then 40 mg/EOW (n=47). Patients were then enrolled in an open-label trial for an additional 48 weeks of therapy at the same dose. At week 48 of the extension study (60 weeks of therapy in the extension study), PASI 75 was achieved in 73% of the 40 mg/wk patients, 67% of the 40 mg/EOW patients, and 50% of the placebo/adalimumab 40 mg/EOW patients (Figure 6).
Figure 6. Adalimumab: PASI 75 response in 48-week extension trial.11
Blum et al examined the durability of treatment response in patients with moderate to severe psoriasis following withdrawal from or a dose reduction in adalimumab therapy.12 One hundred forty-eight patients with a PASI score of ≥8 were enrolled. All patients began therapy in an open-label fashion and received adalimumab 80 mg SC at weeks 0 and 1, followed by 40 mg/wk until the end of week 11. At week 12, patients who achieved a PASI 50 or better were randomized into the double-blind phase of the study and received either adalimumab 40 mg/EOW or placebo for an additional 12 weeks. One hundred thirty-six patients were randomized at week 12. At week 24, there were no cases of rebound, defined as a PASI more than 125% of baseline or the development of generalized pustular or erythrodermic psoriasis. In contrast, 21 patients in the placebo group (31%) and 11 (16%) in the adalimumab group experienced relapse by week 24.
In the third study, Menter et al evaluated the efficacy of adalimumab in psoriasis patients with or without psoriatic arthritis.13 A total of 148 patients were enrolled in a 12-week double-blind placebo-controlled trial and the first 12 weeks of a 48-week extension trial. During the 12-week treatment period, patients received either adalimumab 80 mg at week 0 followed by 40 mg/EOW beginning at week 1, adalimumab 80 mg at weeks 0 and 1 followed by 40 mg/wk beginning at week 2, or placebo weekly beginning at week 0. At weeks 12 and 24, patients with psoriatic arthritis did not appear to respond as well as those without psoriatic arthritis.
Alefacept
Menter at al presented results from an analysis of the long-term use of alefacept in patients who have received multiple courses of therapy.14 This analysis included patients from the intravenous (IV) and intramuscular (IM) phase 3 studies and their open-label extension studies, in which eligible patients received additional courses of alefacept therapy at the same dosage regimen as in the 12-week single-course study in which they participated (the IV formulation is no longer commercially available in the US). In the phase 3 study of IV alefacept, there were 521, 327, 217, 158, and 39 patients who received 1, 2, 3, 4, and 5 courses, respectively. The analysis concluded that a second course of IV alefacept resulted in an improved response in half of the patients who did not achieve PASI 50 or PASI 25 in the first course of therapy and that incremental improvement was seen with successive courses of therapy (Figure 7). The data from a phase 3 study of IM alefacept supported the concept of clinical improvement in psoriasis with multiple courses of alefacept. Four hundred fifty seven, 320, 156, 100, and 50 patients received 1, 2, 3, 4, and 5 courses, respectively. The proportion of patients who achieved a PGA response rating of clear or almost clear increased from 21% during course 1 to a maximum of 41% during course 4.
Figure 7. Alefacept: PASI 75 response rates at any time during each course of IV therapy.14
Efalizumab
Two posters presenting the efficacy data of efalizumab were also highlighted at this meeting.7,15 Gottlieb et al presented a poster describing the efficacy of 36 months of continuous efalizumab therapy in patients with moderate to severe chronic plaque psoriasis.7 This was the final analysis of an open-label, phase 3b study for which interim analyses had been presented previously. Patients were randomized in a 1:1 ratio to receive either a concomitant topical corticosteroid or petrolatum during weeks 9 to 12 of the initial 3-month treatment period. The concomitant use of topical therapies and/or UVB was also allowed during maintenance treatment. Importantly, the concomitant use of systemic psoriasis therapies was excluded. Those patients who received such a systemic psoriasis therapy were included in the efficacy analysis until the segment during which they received the excluded therapy, after which they were considered nonresponders and had their last observation carried forward in the analysis. Patients received efalizumab 2 mg/kg weekly for the first 3 months, and those who achieved at least a PASI 50 or a static PGA of mild, minimal, or clear at month 3 could enroll in the maintenance treatment period and receive up to 33 additional months of efalizumab treatment. The Maintenance Group Intent-to-Treat (MITT) analysis (290 patients) included all patients who entered the maintenance treatment period. At month 6, a PASI 75 and 90 response was demonstrated in 51% and 22% of patients, respectively. At month 33, 55% of patients demonstrated a PASI 75 response, with 31% of patients achieving a PASI 90 response. Thus, patients maintained their response to therapy and, based on the increase in percentage of patients achieving PASI 90, the response appears to improve over time (Figure 8).
Figure 8. Efalizumab: PASI 75 and PASI 90 responses.7
The efficacy of efalizumab in high-need psoriasis patients was presented by Papp et al.15 This was a randomized, placebo-controlled trial designed to analyze a large cohort of high-need patients (526 patients), defined as those patients unable to use at least 2 currently available systemic agents because of lack of efficacy, intolerance, or contraindication. The percentage of patients achieving PASI 75 in the high-need patient population was 30% at week 12 and 31% in the overall population. Both groups demonstrated a PASI 50 in 52% to 54% of patients.
|
|
 |
|
