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Meetings/Links : Meeting Reports : New Information on Biologic Agents and Fumaric Acid
New Information on Biologic Agents and Fumaric Acid

The information in this summary is based on presentations made at an
international meeting held June 10-13, 2004 in Toronto, Ontario, Canada

Alan Menter, MD
Chief, Division of Dermatology
Baylor University Medical Center
Clinical Professor of Dermatology
University of Texas Southwestern Medical School
Dallas, Texas

Kim A. Papp, MD, PhD, FRCPC
Director of Research
Probity Medical Research
Waterloo, Ontario, Canada

This report presents the highlights of an international meeting on the latest treatments for psoriasis. It will focus on new information that was presented on the biologic agents and fumaric acid.

In a comprehensive symposium, Dr. Gottlieb presented the results of two pilot studies that demonstrated that alefacept could produce significant improvements in joint symptoms in patients suffering from either psoriatic1 or rheumatoid arthritis2,3. In the psoriatic arthritis trial, 66.3% of alefacept patients achieved ACR 20 and 29.4% achieved ACR 50 1 week after the completion of 12 weeks of alefacept therapy. In the rheumatoid arthritis trial, 67% of alefacept patients (compared to 17% with placebo) achieved ACR 20 at any time during either 12 weeks of alefacept treatment or 12 weeks of follow-up.

The latest thinking on psoriasis flare, relapse, and rebound seen with efalizumab treatment was discussed by Dr. Menter.4,5 Dr. Menter defined flare as a worsening of psoriasis at any time, relapse as a loss of at least 50% of PASI improvement achieved between baseline and the end of therapy, and rebound as a PASI >125% of baseline or new generalized pustular, erythrodermic, or more inflammatory psoriasis occurring within 3 months of discontinuing treatment. Data from a retrospective analysis of four clinical trials indicated that the patients most likely to experience rebound were those who did not respond to efalizumab therapy. He also described how the risk of rebound can be reduced by transitioning these patients to another psoriasis therapy when efalizumab is stopped. Dr. Carey presented the results of a study on tapering the dose of efalizumab and indicated that this may lengthen the time to relapse but that it did not decrease the rebound rate.6 Dr. Menter also discussed these findings and stressed that the dose of 1 mg/kg/wk is the recommended dose and should not be altered. Dr. Toth and Dr. Papp presented case reports of two patients who rebound after efalizumab therapy, which successfully controlled after a short course of either methotrexate or cyclosporine.7

Another poster on efalizumab included a description by Dr. Hamilton of two patients who were successfully transitioned onto efalizumab therapy from either cyclosporine or etanercept treatment by continuing the patient's previous treatment until an efalizumab effect was observed.8 There was also a presentation by Dr. Papp on the use of efalizumab in psoriatic arthritis.9 In this study, the percentage of patients achieving ACR 20 was not significantly different in the efalizumab and placebo treatment groups, although Dr. Papp pointed out that this study was too short and inadequately powered to definitively demonstrate a lack of efficacy.

Injection-site reactions are the most common adverse effect seen during etanercept therapy. Dr. Griffiths and colleagues described how the incidence of injection-site reactions declined from 14%-16% of patients during the first 12 weeks of etanercept therapy to 4%-7% during weeks 13 to 24.10

Infliximab is being investigated for the treatment of psoriatic arthritis, and Dr. Papp presented a study that showed that infliximab (5 mg/kg at weeks 0, 2, and 6, and every 8 weeks thereafter) produced improvements in psoriatic arthritis that were evident at week 14 (ACR 20 in 58% of patients) and week 24 (ACR 20 in 54% of patients)11. In addition, 63.9% of patients in this study achieved PASI 75 and almost 15% achieved PASI 100 at week 14; these findings are similar to the efficacy rates seen in earlier clinical trials of infliximab in psoriasis patients.

Dr. Wallace and colleagues presented two posters that demonstrated the beneficial effects of adalimumab on health status and quality-of-life measures. Adalimumab was shown to produce greater improvements in both the physical and mental health components of the SF-3612 and in all components of the DLQI13 than did placebo.

A poster presentation by Dr. Langner and colleagues showed that 12 weeks of treatment with an oral formulation of fumaric acid ester produced a statistically significant reduction from the mean baseline PASI in patients with moderate to severe psoriasis.14 Treatment with the 720-mg dose produced PASI 75 in 42% of patients and was well tolerated.

A poster by the Canadian Psoriasis Expert Panel presented the consensus findings from this organization regarding the place of biologic agents in psoriasis therapy.15 They recommended that the current stepwise treatment paradigm for moderate to severe psoriasis be replaced with a new patient-focused treatment algorithm. This algorithm suggests that all treatment options, including biologic agents, be considered equally from the beginning and that appropriate therapy be identified according to the patient's individual needs and circumstances.

In summary, the new information provided at this meeting helps to further distinguish the different antipsoriasis agents from each other and may help physicians to be better able to find the most appropriate and effective therapy for individual patients.

References
  1. Gottlieb A. Expanding the use of biologic therapies in dermatology. In: Selective T-cell targeting with biologics in dermatology: increasing clinical evidence [symposium]. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada.
  2. Schneider M, Stahl H-D, Vaishnaw AK, et al. A pilot study of the safety and efficacy of alefacept in subjects with active rheumatoid arthritis on methotrexate. Presented at: EULAR 2003; June 18-21, 2003; Lisbon, Portugal. OP0111.
  3. Schneider M, Stahl H-D, Podrebarac T, et al. Tolerability and safety of combination methotrexate and alefacept in rheumatoid arthritis: results of a pilot study. Presented at: 62nd Annual Meeting of the American Academy of Dermatology; February 6-11, 2004; Washington, DC. Poster.
  4. Menter A, Kardatzke D, Rundle A, et al. Incidence and prevention of rebound upon efalizumab discontinuation. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada. Poster 34.
  5. Menter A, Cather JC. Recent developments with a T-cell agent for the treatment of psoriasis: approaches to discontinuation of therapy [symposium]. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada.
  6. Carey W, Rundle AC, Kwon P, et al. Taper regimens in the management of patients discontinuing efalizumab therapy. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada. Poster 29.
  7. Toth DP, Papp KA. Managing recurrence of psoriasis following abrupt withdrawal from efalizumab therapy. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada. Poster 31.
  8. Hamilton TK. Initiating efalizumab therapy in patients currently treated with other systemic therapies. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada. Poster 30.
  9. Papp KA, Mease PJ, Garovoy MR, et al. Efalizumab in patients with psoriatic arthritis: results of a phase II, randomized, double-blind, placebo-controlled study. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada. Poster 28.
  10. Griffiths CEM, Tyring S, Xia HA, et al. Injection site reactions in patients with psoriasis receiving etanercept therapy are low in incidence and mild to moderate in severity. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada. Poster 7.
  11. Papp KA. Biologics—exploring new frontiers in the treatment of psoriasis: hot off the press—a biologic update [symposium]. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada.
  12. Wallace K, Miller B, Heffernan M, et al. Results of the SF-36 general health status measure in moderate to severe chronic plaque psoriasis patients treated with adalimumab for 12 weeks. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada. Poster 51.
  13. Wallace K, Hamlin R, Langley R, et al. Results of the Dermatology Life Quality Index in moderate to severe plaque psoriasis patients receiving 12 weeks of adalimumab therapy. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada. Poster 52.
  14. Langner A, Roszkiewicz J, Baran E, et al. Efficacy and safety of a new oral formulation of fumaric acid ester for the treatment of moderate to severe psoriasis. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada. Poster 38.
  15. Canadian Psoriasis Expert Panel. Integrating biological therapies into management of moderate to severe psoriasis: a consensus statement from a Canadian Expert Panel. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada. Poster 27.