Etanercept (Enbrel; Amgen)
Recognition that the pro-inflammatory cytokine tumor necrosis factor-α (TNF-a) is overproduced in patients with various inflammatory disorders, including psoriasis, has led to the development of a soluble recombinant human TNF-a-receptor fusion protein that competitively inhibits the interaction of TNF-α with cell surface receptors. Based on the success of anti-TNF-α treatment in rheumatoid arthritis (RA), a 12-week, randomized, double-blind, placebo-controlled study assessed the efficacy of etanercept in 60 patients with psoriatic arthritis and psoriasis skin lesions. Administration of etanercept 25 mg SC twice weekly was significantly more effective than placebo in all measures of disease activity associated with arthritis as well as in PASI score improvement.10
In a phase III, multicenter, placebo-controlled, double-blind, parallel group trial, the efficacy of etanercept in three different SC dosing schedules was evaluated. At the end of 12 weeks, a 75% improvement in PASI was achieved by 14% of those in the low-dose (25 mg once weekly) etanercept group, 34% in the medium-dose (25 mg twice weekly) group, and 49% in the high-dose (50 mg twice weekly) group, compared with 4% in patients who received placebo. Thereafter, patients in the placebo group began double-blind treatment with etanercept at
a medium dose, and all patients continued therapy for an additional 12 weeks. At week 24, 33% of patients initially in the placebo group achieved a 75% improvement in PASI. For patients initially assigned to the treatment groups, clinical responses continued to improve. At week 24, 75% improvement was achieved by 25% of the patients in the low-dose group, 44% in the medium-dose group, and 59% in the high-dose group.11
Adverse effects observed were similar in patients receiving either etanercept or placebo.10-12 There seems to be a worsening of infections with etanercept use, especially TB. Therefore, patients should have a purified protein derivative (PPD) test before being beginning therapy. In addition, there are rare reports of multiple sclerosis (MS) induction. Etanercept may also worsen congestive heart failure (CHF) and increase the risk of developing lymphoma. Although data regarding long-term safety in patients with psoriasis are not available, clinical studies in more than 2000 RA patients who received etanercept for up to five years have demonstrated continued efficacy and a favorable risk/benefit profile, suggesting that long-term treatment with etanercept may be a viable option for patients with psoriasis.11,12
Infliximab (Remicade; Centocor)
Infliximab is a humanized, chimeric, monoclonal antibody that neutralizes TNF-α. The efficacy of infliximab was evaluated in a double-blind, 10-week phase II trial in which 33 patients with moderate-to-severe plaque psoriasis involving at least 5% of the body surface area were randomly assigned to receive placebo or a three-dose induction regimen of infliximab 5 or 10 mg/kg at weeks 0, 2, and 6. At 10 weeks, a significantly higher number of patients in the infliximab 5-mg/kg (82%) and 10-mg/kg groups (73%) had at least 75% improvement in the PASI score, compared with patients in the placebo group (18%). The difference between the infliximab 5- and 10-mg/kg doses with regard to efficacy was not clinically important.13
Following completion of the 10-week double-blind phase, an open-label extension was carried out to assess the durability of the clinical benefit after the initial three-dose induction regimens. During weeks 10-26, patients who responded initially were evaluated for relapse (loss of at least half the improvement in PASI score at week 10) and re-treated with open-label infliximab (5 or 10 mg/kg ) as needed. Placebo nonresponders were treated with an induction regimen of infliximab (5 or 10 mg/kg) and followed through week 26. In all, 29 of the 33 patients received either 5 or 10 mg/kg of infliximab in the open-label extension. At week 26, PASI response was maintained in 40% and 73% of patients receiving 5 and 10 mg/kg of infliximab, respectively.14 Overall, the study series suggests that infliximab, administered in a three-dose induction regimen of either 5 or 10 mg/kg at weeks 0, 2, and 6, produces a rapid, effective, and sustainable (through week 26) effect that is associated with decreases in epidermal inflammation and normalization of keratinocyte differentiation in patients with moderate-to-severe psoriasis.13,14
Infliximab is not yet approved for the treatment of psoriasis. In a recent phase II trial, 249 patients with a baseline PASI >12 and at least 10% involvement of body surface area were randomized in a 1:2:2 ratio to receive infusions of placebo, infliximab 3 mg/kg , or infliximab 5 mg/kg at weeks 0, 2, and 6. At week 10, a 75% PASI improvement was achieved by 6% of patients in the placebo group compared with 72% of those in the infliximab 3-mg/kg group and 88% in the infliximab 5-mg/kg group.15
Infliximab has been associated with infusion reactions and infections, including rare serious infections and reactivation of TB.3,14 Patients taking the drug should have a PPD test before starting therapy. Other findings common to etanercept and infliximab are rare reports of MS induction as well as possible exacerbation of CHF and increase in the risk of developing lymphoma. Infusion-site reactions (erythema) occur in about 5% of cases and may be severe.
Adalimumab (Humira; Abbott)
Adalimumab, a purely human IgG1 monoclonal TNF-α antibody has been approved as a second-line agent, alone or in combination with a disease-modifying antirheumatic drug, for the treatment of RA. In a recent phase II trial of >100 participants, psoriasis patients taking adalimumab experienced statistically greater improvement in PASI than those taking placebo, and more patients on adalimumab achieved 75% improvement in their PASI than those on placebo.16 Adalimumab is given in a dose of 40 mg SC every other week.
Dr. Scheinfeld is assistant attending and assistant clinical professor at St. Luke’s-Roosevelt Hospital Center and Beth Israel Medical Center, Department of Dermatology, and Ms. Mikhail is a student at New York University School of Medicine, all in New York City.
1. Greaves MW, Weinstein GD. Treatment of psoriasis. N Engl J Med. 1995;332:581-588.
2. Lebwohl M, Heymann W, Berth-Jones J, et al. Treatment of Skin Disease. New York, N.Y.: Mosby International; 2002.
3. Weinberg JM. An overview of infliximab, etanercept, efalizumab and alefacept as biologic therapy for psoriasis. Clin Ther. 2003:25:2487-2505.
4. National Psoriasis Foundation: Biologic treatments chart.
5. Ellis CN, Krueger GG; Alefacept Clinical Study Group. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med. 2001; 345:248-255.
6. Krueger GG, Papp KA, Stough DB, et al. A randomized, double-blind, placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis. J Am Acad Dermatol. 2002;47:821-833.
7. Lebwohl M, Christophers E, Langley R, et al. An international, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis. Arch Dermatol. 2003;139:719-727.
8. Lebwohl M, Tyring SK, Hamilton TK, et al. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med. 2003;349:2004-2013.
9. Gordon KB, Papp KA, Hamilton TK, et al. Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial. JAMA. 2003;290:3073-3080.
10. Mease PJ, Goffe BS, Metz J, et al. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet. 2000:356:385-390.
11. Leonardi CL, Powers JL, Matheson RT, et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med. 2003;349:2014-2022.
12. Gottlieb AB, Matheson RT, Lowe N, et al. A randomized trial of etanercept as monotherapy for psoriasis. Arch Dermatol. 2003;139:1627-1632.
13. Chaudhari U, Romano P, Mulcahy LD, et al. Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial. Lancet. 2001;357:1842-1847.
14. Gottlieb AB, Chaudhari U, Mulcahy LD, et al. Infliximab monotherapy provides rapid and sustained benefit for plaque-type psoriasis. J Am Acad Dermatol. 2003;48:829-835.
15. Gottlieb AB, Li S, Evans R, et al. Infliximab in the treatment of psoriasis: results from the first 10 weeks of a phase II trial. Poster presented at: American Academy of Dermatology 61st Annual Meeting; March 21-26, 2003; San Francisco, Calif.
16. Chen DM, Gordon K, Leonardi C, Menter A. Adalimumab efficacy and safety in patients with moderate to severe chronic plaque psoriasis: preliminary findings from a 12-week dose-ranging trial. J Am Acad Dermatol. 2004;50(Pt 2):P2.