Source: DGNews  |  Posted 4 years ago

By Pam Harrison

TORONTO, CANADA -- July 4, 2007 -- Patients with plaque psoriasis who do not tolerate or whose disease is inadequately controlled by one biological agent may respond to another, researchers suggest, citing several success stories that support a switch policy when results are less than optimal.

Several case reports presented here at the Canadian Dermatology Association 82nd Annual Conference indicate that patients who have an inadequate response to etanercept can experience "suitable efficacy" when switched to efalizumab. It has also been suggested that patients who are inadequately controlled by alefacept may similarly benefit from a switch to efalizumab.

Aditya Gupta, MD, associate professor of medicine, University of Toronto, Toronto, Ontario, Canada, cites two case reports in which switching from alefacept 15 mg/week IM to efalizumab at an initial dose of 0.7 mg/kg followed by subcutaneous injections once weekly of 1 mg/kg resulted in a change from a baseline Psoriasis Area and Severity Index (PASI) score of 30.4 to 3.2 after 16 weeks of efalizumab.

Dr. Gupta cites a second case in which the patient was again switched from the same dose of alefacept as in the first case to the same dose of efalizumab. The PASI score in this patient decreased from 11.1 at baseline to 2.6 at weeks 12 and 16.

"After 3 to 4 months of use, efalizumab use provided each subject with nearly complete reductions in PASI score," Dr. Gupta observes, "and these two case reports indicate that efalizumab can provide effective therapy for subjects who did not have sufficient efficacy with alefacept."

A relatively critical look at the literature in which the four currently approved biological agents were assessed in patients with "difficult-to-treat" psoriasis suggests that all four agents do not perform equally well, at least in this patient subgroup, according to a presentation by Charles Lynde, assistant clinical professor of medicine, University of Toronto.

All currently approved biological agents target the immune response that gives rise to psoriasis, Dr. Lynde says. Nevertheless, their mechanism of action is not identical: alefacept and efalizumab act directly on T cells, while etanercept and infliximab antagonise proinflammatory signalling by tumour necrosis factor alpha (TNF-a). These differences appear to have variable effects in patients with plaque psoriasis, at least in difficult-to-treat psoriasis, he explained.

In a paper on one prospective study of infliximab in difficult-to-treat psoriasis, researchers with the Canadian Expert Drug Advisory Committee (CEDAC) acknowledged that a significant improvement was seen following the induction regimen, where mean PASI scores decreased from 26.5 at baseline to 3.9 after induction.

However, response to infliximab faded with time, from 77% of patients achieving a PASI-75 score at week 10 to 44% having a PASI-75 score by week 50.

The CEDAC authors also noted that infliximab is associated with a high incidence of serious adverse events -- up to 25% in some studies in moderate to severe psoriasis and in difficult-to-treat patients.

Only one retrospective study exists that explored the use of etanercept in patients with difficult-to-treat psoriasis. At a dose of 25 mg twice a week for 12 weeks -- the approved dose in Europe -- 21% of this particular cohort achieved a PAASI-75. (Response rate to 50 mg etanercept, twice weekly, was very similar at 23%).

As for alefacept, a prospective, randomised, placebo-controlled study exists for a sizeable number of difficult-to-treat patients (N = 195). After 12 weeks of alefacept 15 mg IM, a comparison of responses at week 14 (2 weeks after the 12-week study was completed), 9% of those on active therapy achieved a PASI-75 score versus 5% of placebo controls, not significantly different responses.

In contrast, the PASI-50 response was significantly greater for alefacept recipients in this particular study at 24% versus 11% for placebo. Interestingly, improvement in quality of life did not differ between the two treatment arms.

The Clinical Experience Acquired with Raptiva (CLEAR) study prospectively examined the use of efalizumab in 526 patients with difficult-to-treat disease.

Results from CLEAR showed that approximately 30% of difficult-to-treat patients achieved a PASI-75 score at week 12 -- the same percentage as was achieved by the total patient population. Improvements in quality of life were also similar between patients with difficult-to-treat psoriasis and those with moderate-to-severe psoriasis in the rest of the population. PASI-75 responses and mean PASI improvements were again comparable between the difficult-to-treat group and the rest of the CLEAR extension cohort with an additional 12 weeks of treatment. Notably, two thirds of patients in the extension trial fell into the difficult-to-treat category.

Based on these findings, CEDAC determined that treatment with efalizumab does offer significant improvements over placebo and improves quality of life; as such, the cost of treatment, in their view, should be reimbursed if patients have severe disease or significant involvement of the hands, feet, face, or genital area. Patients for whom methotrexate, cyclosporine, or phototherapy are ineffective, intolerable, or contraindicated should also be candidates for efalizumab therapy.

CEDAC does, however, acknowledge that "restricting biological agents to these patient subgroups is at odds with previous Canadian guidance on treatment of moderate to severe psoriasis."

[[]Presentation titles: Efficacy of Efalizumab in Psoriasis Patients Inadequately Controlled by Alefacept. Use of Biologicals Among Patients With Difficult-to-Treat Moderate to Severe Psoriasis: Presented at CDA[]]