May 15, 2006 • www.internalmedicinenews.com Dermatology Clinical Rounds 39 Extended Efalizumab for Psoriasis Well Tolerated

BY SHERRY BOSCHERT ty Index (PASI) of the patients was at least 12 at baseline; most often within 48 hours of efalizumab injection, and San Francisco Bureau their mean PASI was 19. At least 10% of their body sur- consisted primarily of headache, fever, chills, nausea, face area was affected; the mean was 29%. pharyngitis, and a flulike syndrome. The percentage of S AN F RANCISCO — Efalizumab appears to be well tol- One study was a 60-week randomized, double-blind, patients experiencing an adverse event then gradually de- erated over the course of up to 60 weeks of treatment, parallel-group, placebo-controlled trial. Included in the creased to 48% among the 537 patients followed for 49- according to a combined analysis of more than 1,000 pa- pooled analysis were 450 patients who had been ran- 60 weeks, Dr. Gottlieb wrote. tients with moderate to severe chronic plaque psoriasis. domized to receive efalizumab Infections occurred in 20%-30% Common adverse events were similar to those seen in during the 12-week placebo-con- Common adverse of patients during each of the five shorter trials; no new category of common adverse event trolled portion of the trial and 218 events were evaluation periods. Arthritis oc- appeared during extended therapy periods, Dr. Alice B. who were randomized to receive similar to those curred in 1%-3% of patients Gottlieb reported in a poster session at the annual meet- placebo. Both groups entered an seen in shorter throughout the five periods. ing of the American Academy of Dermatology. open-label extended-treatment trials; the risk of Serious adverse events were not- The risk of serious adverse events did not increase over phase for up to 48 weeks of active serious events did ed in 2%-3% of patients during time, added Dr. Gottlieb of the University of Medicine treatment, and then were eligible not rise over time. each 12-week segment. The inci- and Dentistry of New Jersey, New Brunswick, N.J. Dr. to continue to receive the drug for dence of each serious event was Gottlieb is a paid consultant for Genentech Inc., which another 12 weeks or until the drug DR. GOTTLIEB less than 1%, except for serious makes efalizumab (Raptiva). The Food and Drug Ad- became commercially available. skin-related problems, which ministration approved the biologic agent for the treat- The second study included in the pooled analysis was peaked at 1% during the 37-48 week exposure period. ment of moderate to severe psoriasis in October 2003. an open-label 36-month trial. The investigators evaluat- There was one case of hemolytic anemia that occurred The analysis appears to be the largest compilation of ed safety data for up to 60 weeks of therapy for 339 of with 25-36 weeks of exposure. Eight cases of thrombo- psoriasis patients studied through 60 weeks of treatment the patients. cytopenia were reported; two occurred during the first with a biologic therapy. Concomitant use of topical psoriasis therapy or pho- 12 weeks of exposure, three with 13-24 weeks, two with Dr. Gottlieb and her associates evaluated the long-term totherapy was permitted at various periods in both stud- 25-36 weeks, and one with 37-48 weeks of exposure. safety of efalizumab, injected subcutaneously at weekly ies. For analysis, the investigators divided treatment The incidence of malignancy remained at less than 1% intervals, by pooling the 60-week data from two multi- phases into five consecutive 12-week segments. During throughout. The most common malignancy was non- center phase III studies of adults with moderate to severe the first 12-week exposure period, 80% of 1,004 patients melanoma skin cancer, of which there were 18 cases, Dr. chronic plaque psoriasis. The Psoriasis Area and Severi- experienced at least one adverse event. These occurred Gottlieb reported. ■ New Psoriasis Drugs May Boost Compliance Adalimumab Helps

BY BRUCE JANCIN The prospect of better compliance is alone. The tolerability profile was sim- Skin Disease in Denver Bureau also a major selling point for the combi- ilar to betamethasone monotherapy and nation calcipotriene/betamethasone better than with calcipotriol alone (J. Psoriatic Arthritis K OLOA, HAWAII — With the pletho- dipropionate approved by the FDA ear- Eur. Acad. Dermatol. Venereol. 2006; ra of topical clobetasol propionate for- lier this year. The two drugs aren’t ordi- 20:39-44). S AN F RANCISCO — Adalimumab is ef- mulations already on the market, why narily compatible due to differing pH re- The studies demonstrated Taclonex fective in treating both mild to moderate do physicians and patients need the re- quirements. However, Warner-Chilcott was effective not only for acute flares, and moderate to severe skin disease in pa- cently approved Clobex spray that’s now came up with a water-free vehicle that al- but also as maintenance therapy in a 52- tients with psoriatic arthritis, Dr. Dafna D. reaching pharmacy shelves? lows for a stable combined product. week trial. Gladman reported in a poster presentation at “Compliance, compliance, compli- In the United States, the combination “Also, for those of us who do not feel the annual meeting of the American Acade- ance,” Dr. Chai Sue Lee said at the an- is known as Taclonex. In Europe and comfortable prescribing a class-2 steroid my of Dermatology. nual Hawaii Dermatology Seminar Canada, where it has been available as like betamethasone for long-term main- Adalimumab, a tumor necrosis factor sponsored by the Skin Disease Educa- Dovobet or Daivobet for several years, tenance, another strategy would be to blocker, was approved in 2005 for the treat- tion Foundation. switch to intermittent therapy ment of rheumatoid arthritis and psoriatic A 2005 survey from the Nation- Some patients will find the new with weekday calcipotriol and arthritis. To assess whether the level of skin al Psoriasis Foundation showed that weekend Taclonex, or even just disease affected the response of psoriasis to 73% of psoriasis patients, regardless clobetasol propionate 0.05% spray calcipotriol monotherapy once the drug, Dr. Gladman and her associates per- of disease severity, are less than (Clobex spray) more user friendly than the disease has been gotten un- formed a post-hoc analysis of a 24-week, “very satisfied” with their current der control,” Dr. Lee said. placebo-controlled phase III trial of patients treatment. other formulations of the drug. Yet another intriguing devel- with moderately active to severely active pso- Clobetasol propionate is already opment in topical therapy is an riatic arthritis. the most commonly prescribed topical it has rapidly grabbed market share. over-the-counter (OTC) hydrogel patch Among those in the adalimumab-treated corticosteroid for moderate to severe The widespread use is attributed in part modified by the addition of an imper- group, 53 patients had mild to moderate skin psoriasis in the United States and Eu- to the fact that the combination product meable coating on one side. The goal is disease, with a Psoriasis Area and Severity In- rope. Some patients will find the new is highly effective as once-daily therapy, an inexpensive, user-friendly form of dex (PASI) score of less than 10 at baseline; clobetasol propionate 0.05% spray which confers a significant compliance occlusive therapy for psoriasis. 16 patients had moderate to severe skin dis- (Clobex spray) more user friendly than advantage over other psoriasis topicals. Preliminary results of a 120-patient, ease, with a PASI score of 10 or more. other formulations of the drug. And in- Moreover, once-daily dosing means half open-label right/left comparison study PASI responses occurred quickly and were creased patient satisfaction is likely to the exposure to drug side effects, com- by University of California, San Fran- maintained. After 24 weeks of drug treat- translate into improved treatment com- pared with twice-daily dosing, as well as cisco, dermatologists showed that the ment, the two subgroups had similar re- pliance, explained Dr. Lee, director of lower medication volume and cost, Dr. patch readily covered hard-to-wrap areas sponse rates. Comparing the mild/moderate the psoriasis treatment center at the Lee continued. such as the elbow. The patch alone re- and moderate/severe groups, a PASI 50 score University of California, Davis. Taclonex is one of the most exten- sulted in substantial improvement in (a 50% reduction from baseline) was achieved In two multicenter phase III random- sively studied topical agents in the mild psoriasis lesions. Moreover, when by 39 (74%) and 13 (81%), respectively; a PASI ized, double-blind, vehicle-controlled, world. It has been the subject of seven the patch was applied over OTC 1% hy- 90 score was achieved by 23 (43%) and 6 and Galderma-sponsored clinical trials, completed international clinical trials drocortisone, tacrolimus 1% ointment, (38%) in the respective groups, reported Dr. twice-daily Clobex spray resulted in a totaling more than 7,000 psoriasis pa- or more potent topical agents, the result Gladman of the University of Toronto. high rate of durable treatment respons- tients. A recent metaanalysis involving was in every case superior to the drugs Dr. Gladman is a primary investigator for es. Indeed, 72% of Clobex spray re- six of these double-blind randomized tri- alone, according to Dr. Lee. Abbott Laboratories, which makes adali- sponders in one study and 76% in the als totaling more than 6,000 psoriasis pa- Dr. Lee disclosed that she has con- mumab (Humira). other remained clear, almost clear, or tients concluded that 4 weeks of thera- ducted research sponsored by Warner- Both subgroups, she said, achieved “mean- with only mild psoriasis, a full 4 weeks py with the two-compound product Chilcott. ingful improvements” in quality of life, com- after the end of 4 weeks of therapy. Ad- resulted in 65%-74% reductions in the The SDEF and this news organiza- pared with baseline, as measured by the Der- verse events were similar in the Clobex Psoriasis Area and Severity Index, sig- tion are wholly owned subsidiaries of matology Life Quality Index. and control groups. nificantly better than with either agent Elsevier. ■ —Sherry Boschert