18 Arthritis R HEUMATOLOGY N EWS • August 2005 Alefacept Boosts Response Strategy Reduces Need for To Methotrexate in Patients Monitoring Alefacept Users

C HICAGO — Assessing CD4 T cells at the patient’s liver is different,” she said. With Psoriatic Arthritis week 4 during the treatment of psoriasis “Perhaps the increased hepatotoxicity is a with alefacept can reduce the need for result of increased body mass index and ARTICLES BY or malignancies were reported in the ale- further lymphocyte monitoring in some steatohepatitis.” PATRICE WENDLING facept-treated group. patients, Jennifer Cather, M.D., reported at Ongoing trials are evaluating whether Chicago Bureau Longer-term data for psoriasis shows the International Psoriasis Symposium longer treatment with alefacept is needed no increase in malignancies or infec- sponsored by the Skin Disease Education to improve its efficacy, suggesting that C HICAGO — The combination of tions, Dr. Lebwohl noted in an interview. Foundation. long-term monitoring will remain impor- methotrexate and alefacept appears to This suggests that the combination of The strategy could also lower costs and tant for physicians and patients. be safe and effective for the treatment of alefacept and methotrexate may be use- make alefacept therapy more convenient, Early data suggest that the addition of psoriatic arthritis, Mark G. Lebwohl, ful in the long-term management of she added. four doses to the 12-week treatment regi- M.D., said at the 11th International Pso- psoriatic arthritis. Weekly CD4 counts are required by the men increased response rates in patients riasis Symposium, sponsored by the Skin In addition to greater efficacy, it’s alefacept (Amevive) package insert with psoriasis, and that multiple courses Disease Education Foundation. hoped that the combination therapy throughout the 12-week treatment regi- may improve clinical responses in psoria- This is the first study to evaluate ale- would allow for reduced methotrexate men and are done as standard of care. sis patients who fail to show a strong ini- facept in combination with metho- dosages, he said. Dr. Cather suggested that the counts at tial response, she said. trexate in psoriatic Two other bio- week 4 can predict with a high degree of ac- “In addition, there are some data that arthritis, which af- At week 24, 54% of logic therapies, curacy what the counts for weeks 5-12 will show that their duration of remission in fects about 20%- etanercept and in- be. between each course improves with mul- 30% of all psoriasis combination therapy fliximab, have both If the count is more than 600 cells/µL at tiple courses,” said Dr. Cather. patients. patients achieved ACR 20, been used with week 4, there is less than a 0.1% chance of In 197 patients with psoriasis who re- Alefacept methotrexate in having a subsequent CD4 count fall below ceived 264 courses of alefacept at Baylor (Amevive) is ap- compared with 23% of the rheumatoid arthri- 250 cells/µL, Dr. Cather said. University independent of clinical trials, proved for psoria- participants who received tis, allowing for a Therefore, she explained, weekly mon- CD4 counts did not fall below 400 cells/µL sis and demon- reduction in the re- itoring during the remaining treatment in any of the patients, she said. strated clinical methotrexate plus placebo. quired dosage of may be unnecessary in these patients. A total of 109 (41%) of treatments were improvement in an methotrexate. Monitoring should be performed 12-week courses of alefacept in combina- initial pilot in psoriatic arthritis. The rationale for using alefacept is monthly for patients with a count between tion with other therapies, including In this double-blind study, 185 patients that it selectively reduces memory T- 400 cells/µL and 600 cells/µL, and every 2 methotrexate, cyclosporine, hydroxyurea, aged 18-70 years with active psoriatic cells, which may play a role in the weeks if the count is less than 400 cells/µL ultraviolet B light, and acitretin. A total of arthritis despite methotrexate treatment pathogenesis of psoriatic arthritis, said at week 4. 83 (32%) were standard 12-week alefacept for 3 or more months were randomized Dr. Lebwohl, chair of dermatology at If a patient’s CD4 count is less than 250 monotherapy courses; 63 (24%) were ex- to 15-mg alefacept once weekly for 12 Mt. Sinai School of Medicine, New cells/µL at any time during alefacept treat- tended courses of alefacept for 12 or more weeks or placebo. All patients continued York. ment, the drug is usually withheld and test- weeks either as monotherapy or in com- on methotrexate at various dosages. Synovial fluid analyses from psoriatic ing should be done weekly until the count bination with other agents; and 8 (3%) At week 14, 53% of patients in the ale- arthritis patients have shown a reduction is 250 cells/µL or greater. were double-dose or alternative-dosing facept group achieved a 50% or greater in CD4+ and CD8+ cells from baseline The recommendations are from a pro- regimens. improvement according to scores on the following treatment with alefacept. Oth- posed monitoring algorithm based on a The most common adverse events were Psoriasis Area and Severity Index (PASI er T-cell therapies, such as cyclosporine, mathematical model and later confirmed fatigue, joint pain, aches, and chills. 50), compared with 17% of the placebo also have shown some benefit in psori- at Baylor University Medical Center at There were five cases of infection, four group. atic arthritis patients. Dallas, where Dr. Cather is codirector of malignancies including three skin cancers At week 24, 54% of the alefacept/ Although it’s not surprising that ther- the cutaneous lymphoma and graft vs. and one case of lung cancer, and no cases methotrexate–treated patients achieved apies targeting T cells might be of ben- host disease clinic. of liver or kidney toxicity. at least a 20% improvement according efit in psoriatic arthritis, Dr. Lebwohl Biogen Idec, which makes alefacept, re- Dr. Cather noted that in a recent case re- to American College of Rheumatology noted that a recent efalizumab (Rapti- vised its package insert for the biologic last port of alefacept in two patients with he- response criteria (ACR 20), compared va) trial involving psoriatic arthritis pa- year after concerns were raised about seri- patitis C infection and psoriasis, decreases with 23% of the investigation partici- tients did not show similar significant ous liver injury in two patients. It is im- in CD4 and CD8 counts were transient, pants who received methotrexate plus benefits. portant to monitor for liver enzyme eleva- and were not associated with either an in- placebo. Dr. Lebwohl is a consultant, speaker, tions in patients with psoriasis and psoriatic crease in hepatitis viral loads or exacerba- Results on both efficacy end points and investigator for Biogen Inc., which arthritis, said Dr. Cather, who has received tion of infection (Br. J. Dermatol. were statistically significant, he said. markets alefacept. The SDEF and this funding support from Biogen Idec. 2005;152:1048-50). The incidence of serious adverse newspaper are wholly owned sub- “I think that the hepatotoxicity that we The SDEF and this newspaper are whol- events was 2%, and no serious infections sidiaries of Elsevier. ■ see with a lot of these biologics is because ly owned subsidiaries of Elsevier. ■ Etanercept Found Safe in Patients With Concurrent Hepatitis C

N EW O RLEANS — Etanercept appears to be a safe University. In the other patient, a significant elevation preventing soluble TNF-α and TNF-β from binding to therapeutic option in psoriasis patients with concurrent was noted only in alanine transaminase and not in the their receptors. hepatitis C, according to the results of a retrospective case transaminase levels. The case series joins a very limited amount of litera- series. All patients showed marked improvement of their ture evaluating the use of etanercept (Enbrel) in patients “Not only does it appear to be safe, it might even be psoriasis, with three of the five patients becoming with rheumatoid arthritis (RA) or psoriasis and concur- beneficial for the patient’s underlying hepatitis,” Erin J. “clear” or “almost clear” on the physicians’global as- rent hepatitis C (HCV). Allen, M.D., proposed during a poster presentation at the sessment. According to the literature, treatment with etanercept annual meeting of the American Academy of Derma- Two patients experienced a flare when started on in- did not worsen the underlying hepatitis in three psoria- tology. terferon, but still tolerated the interferon, and psoriasis sis patients (J. Am. Acad. Dermatol. 2004;51:580-4) and Hepatitis viral loads decreased in two of the five pa- remained less than 10% of body surface area. improved the serum transaminases and viral loads in tients receiving etanercept (Enbrel) 25 mg twice weekly Etanercept, an anti–tumor necrosis factor (TNF) some patients with RA and HCV (J. Dermatolog. Treat. for up to 14 months. Three patients had decreased liver therapy, was a rational choice for these patients because 2003;14:229-32). transaminases. TNF is elevated in both hepatitis C and psoriasis, said Although etanercept was generally well tolerated, Of the two patients with elevated transaminases, one Dr. Allen, who has participated in etanercept trials, but Dr. Allen recommended that all psoriasis patients discontinued interferon prematurely just before starting didn’t receive funding for the series. with concurrent hepatitis C be closely monitored in etanercept, so the worsening transaminases were not Although the exact mechanism is not known, etaner- conjunction with a hepatologist until more data are unexpected, said Dr. Allen, a dermatologist at St. Louis cept neutralizes the proinflammatory effects of TNF by available. ■