Two autoimmune biologics were recently approved by the FDA: ustekinumab in September 2009 for the treatment of moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy and tocilizumab in January 2010 for adult patients with moderate to severe rheumatoid arthritis (RA) who have not responded adequately to 1 or more tumor necrosis factor (TNF) antagonist therapies. Both agents use new mechanisms of action and add to the growing group of autoimmune biologics.
To critically review the phase 3 trials for ustekinumab and tocilizumab and provide managed care considerations in the context of the 9 other biologic agents on the market in the United States that are used to treat moderate to severe RA or psoriasis.
A MEDLINE review was performed for articles published and available through January 2010 using keywords "ustekinumab" and "tocilizumab" with an emphasis on phase 3 trials. The literature search was limited to articles in English, clinical trials, randomized controlled trials, and research conducted in humans. Search results for ustekinumab included 8 articles of which 4 were excluded for not being psoriasis or psoriatic arthritis trials. Search results for tocilizumab included 16 articles of which 8 were excluded for not being RA trials or using biomarkers as primary endpoints. Additional information was obtained from the FDA website.
Three phase 3 trials are available for ustekinumab. Ustekinumab demonstrated superior efficacy to placebo in 2 trials for the treatment of psoriasis. In a 12-week trial, ustekinumab 45 milligrams (mg) and 90 mg demonstrated significantly higher rates of 75% improvement in the psoriasis area and severity index (PASI 75) (67.5% and 73.8%, respectively) compared with etanercept (56.8%) in the first phase 3 comparative psoriasis trial between autoimmune biologics (P < 0.05 for both comparisons). In a phase 3 trial of RA patients who had failed prior TNF antagonist therapy, a 20% improvement in signs or symptoms according to the American College of Rheumatology criteria (ACR 20) at week 24 was achieved by significantly more study participants in the tocilizumab 8 mg per kilogram (kg) (50.0%) and 4 mg per kg (30.4%) groups than the placebo group (10.1%, P < 0.001 for both tocilizumab groups compared with placebo). Safety data for ustekinumab are limited to use for less than 2 years, and the prescribing information contains warnings regarding infection and malignancy. Tocilizumab is associated with neutropenia, thrombocytopenia, and elevations in lipids and liver function tests. Tocilizumab has unique adverse events when compared with other autoimmune biologics and requires laboratory testing and careful monitoring.
Ustekinumab and tocilizumab are new additions to the treatment of autoinflammatory disease. The majority of safety data for both agents are from trials lasting 3 to 6 months. Published long-term safety data for tocilizumab are limited to less than 143 patients treated longer than 5 years, and safety data for ustekinumab are scant beyond 2 years of use; therefore, clinicians should exercise caution prior to widespread adoption. The comparative efficacy and safety trial of etanercept and ustekinumab brings important clinical information to decision makers. Tocilizumab is indicated after failure or intolerance to a TNF antagonist and has unique safety concerns. Managed care plans will consider the experience and long-term data of these agents along with efficacy data and cost when establishing management programs such as prior authorization or step therapy.