Novel Treatments for Psoriatic and Rheumatoid Arthritis Show Efficacy
Two arthritis medications have shown efficacy in clinical trials—a phase II trial of brodalumab in the treatment of psoriatic arthritis and a phase III trial of tofacitinib in the treatment of rheumatoid arthritis. The findings were reported in the New England Journal of Medicine.
“There is a need for therapies to effectively treat the various clinical domains of psoriatic arthritis: arthritis, enthesitis, dactylitis, and skin disease as well as prevent permanent joint damage, especially in those patients for whom anti-TNF therapy is not effective or tolerated,” said Philip J. Mease, MD, Chief of Rheumatology Research and Clinical Professor of Medicine, Swedish Medical Center and University of Washington, Seattle.
The phase II study of brodalumab—an investigational human monoclonal antibody against interleukin-17 receptor A—involved 168 patients with at least a 6-month history of psoriatic arthritis who were randomized to brodalumab (140 or 280 mg subcutaneously) or placebo on day 1 and at weeks 1, 2, 4, 6, 8, and 10. At week 12, all patients were offered open-label brodalumab (280 mg) every 2 weeks.
At week 12, a significantly great Similar rates of improvement with brodalumab were found regardless of whether patients had previously received biologic therapy. At week 24, patients who continued brodalumab treatment showed continued improvement (ACR 20, 51% and 64% in the 140-mg and 280-mg groups), and patients who switched from placebo to active treatment also showed significant improvement (ACR 20, 44%).
Serious adverse events were rare in both groups (3% and 2% in the brodalumab and placebo groups, respectively).
“These significant patient responses support continued evaluation of brodalumab for the treatment of psoriatic arthritis and clearly show that cytokine-targeting strategies aimed at blocking signaling through the IL-17 receptor may represent an important new treatment strategy. These beneficial effects further illuminate the importance of the TH17 immunologic pathway in the pathogenesis of psoriasis and psoriatic arthritis,” said Dr. Mease, who lead the study.
The study was supported by Amgen.
"The standard treatment for rheumatoid arthritis [RA] is composed of conventional disease modifying anti-rheumatic drugs [DMARDs, methotrexate is most effective] and biologic agents [TNF inhibitors are most commonly used],” said Eun Bong Lee, MD, PhD, Professor of Medicine in Rheumatology, Seoul National University College of Medicine, Seoul, Korea.
“The efficacy of tofacitinib has been proven in RA patients who showed inadequate response to conventional DMARDs and TNF inhibitors. This study showed superiority over methotrexate in methotrexate-naïve RA patients in the respective of clinical efficacy, structural prevention, and patients’ quality of life. This means that tofacitinib can be useful in most of the spectrum of RA patients,” noted Dr. Lee, who led the current study.
In the phase III study of tofacitinib, 956 patients with active moderate-to-severe rheumatoid arthritis (RA) who were methotrexate naïve were randomized to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate (titrated to 20 mg per week over 8 weeks).2 Tofacitinib is an oral Janus kinase inhibitor that is currently approved to treat adults with moderately to severely active RA who have had an inadequate response to, or who are intolerant of, methotrexate.P<0.001 for both comparisons).
The rate of herpes zoster was higher in the combined tofacitinib groups (4.0%) than in patients who received methotrexate (1.1%). Confirmed cases of cancer were reported in 5 patients who received tofacitinib and 1 patient who received methotrexate. In addition, tofacitinib was associated with increases in creatinine levels and in low-density lipoprotein cholesterol levels as well as reduced in neutrophil and lymphocyte counts.
“Tofacitinib is an oral agent, while current biologic agents are parenteral drugs,” Dr. Lee said. “It is a great advantage for RA patients in whom long-term compliance is required to achieve effective control of the disease,” he noted.
The study was funded by Pfizer.