Along with tumor necrosis factor-alpha (TNF-α) inhibitor etanercept, infliximab is now formally approved by the US Food and Drug Administration (FDA) for active arthritis in patients with psoriatic arthritis (PsA). The third TNF-inhibitor in this class, adalimumab, is currently under review for a PsA indication
"This provides a further option of potent therapy for both joint and skin," Philip J. Mease, MD, clinical professor at the University of Washington and rheumatologist at the Swedish Hospital Medical Center in Seattle, tells CIAOMed. "The skin response is quite striking and the data that is accumulating shows that it's helpful in inhibiting progression of damage as measured by x-ray change that is analogous to what has been shown with etanercept."
Infliximab "is helpful as an additional medication to try for patients who have failed other therapies, and it gives increased flexibility about dosing format in that it is given intermittently intravenously," he says. "With rheumatoid arthritis (RA), patients may respond differently to one TNF inhibitor over another, so having more choices is a great option."
IMPACT 2 data lead to approval
The data that led to the approval decision were obtained from the Induction and Maintenance of Psoriatic Arthritis Clinical Trial 2 (IMPACT 2),1 a Phase III randomized, double-blind, placebo-controlled study of 200 patients with active PsA. Researchers found significant improvements in both American College of Rheumatology (ACR) 20 scoring criteria and Psoriasis Area Severity Index (PASI) in infliximab-treated patients as early as week 2. By week 14, 58% of infliximab-treated patients achieved an ACR20 response versus 11% of placebo-treated patients. At week 24, 27% of infliximab-treated patients experienced at least 70% improvement (ACR70) compared to 2% of placebo-treated patients.
At week 24, 60% of infliximab-treated patients achieved a PASI 75 response compared to 1% of patients on placebo. Furthermore, more than one-third (39%) of patients receiving infliximab achieved PASI 90, while none of the patients on placebo achieved this level of skin clearance.
Patients taking infliximab also experienced a decrease in symptoms of dactylitis and enthesopathy. At baseline, enthesopathy was observed in 42% of patients in the infliximab group and 35% of patients receiving placebo. After 24 weeks of treatment, only 15% of infliximab patients continued to experience symptoms, compared to 33% of patients receiving placebo.
A similar number of patients experienced adverse events in each treatment group, with no deaths, cases of tuberculosis, or other opportunistic infections reported. Infusion reactions were reported in both groups. With the exception of one case of basal cell carcinoma in the placebo group, no malignancies were reported.
"The approval of infliximab is a promising development in the treatment of psoriatic arthritis," said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego in a press release.2 "Study results show that patients treated with infliximab rapidly achieved profound improvement in arthritis symptoms and dramatically improved clearance in skin disease."
In September 2004, infliximab was approved in the European Union in combination with methotrexate for the treatment of active and progressive PsA in patients who have responded inadequately to disease-modifying anti-rheumatic drugs. Infliximab is currently approved for Crohn's disease, RA, and ankylosing spondylitis.
References:
- Antoni C, Krueger GG, de Vlam K et al. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis. 2005 Feb 24; [Epub ahead of print].
- FDA approves RemicadeR for ninth indication: psoriatic arthritis. FDA approves RemicadeR for ninth indication: psoriatic arthritis [press release]. Malvern, Pa: Centocor, Inc; May 17, 2005.