Information on New Drug Approvals and Medication Safety

Fostamatinib is currently in phase III trials for the treatment of F (RA).⁵ Fostamatinib is an oral spleen tyrosine kinase (syk) inhibitor that reversibly blocks signaling in different cell types associated with inflammation and tissue degradation in RA patients.⁶ Current trials are evaluating the long-term safety and efficacy of fostamatinib monotherapy in RA patients. Two different dosing regimens are being studied in patients who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor–α inhibitors; it is also being compared with adalimumab.⁷

Sarilumab, previously known as REGN88, is a novel, high-affinity, subcutaneous, fully human antibody to the interleukin 6 receptor (IL-6R) that is currently in phase III clinical trials for the treatment of active, moderate to severe RA.^8,9 The phase IIb results showed that when combined with MTX (in patients who had an inadequate response to MTX monotherapy), sarilumab+MTX–treated patients demonstrated reduction in signs and symptoms of RA. Also, adverse effects were similar to those previously reported with IL-6 inhibition. In this study, patients (n=306) were randomized to receive sarilumab 100 mg every other week (q2w), sarilumab 150 mg q2w, sarilumab 100 mg weekly (qw), sarilumab 200 mg q2w, sarilumab 150 mg qw, or placebo. The ACR20 response at Week 12 was numerically higher than placebo in all sarilumab-treated groups, and significantly greater in the 150 mg qw sarilumab arm (72%) (versus 46%, placebo; P=0.02). Treatment with sarilumab also increased the total cholesterol, low-density lipoprotein levels, and high-density lipoprotein levels.

The new drug application for tofacitinib, a novel, oral, janus-associated kinase (JAK) inhibitor-3 for treating moderate to severe active RA, has been accepted by the FDA.¹⁰ More than 300 patients (mostly women) were randomized to treatment with tofacitinib 5 mg or 10 mg twice daily for three months. All patients had at least four tender and swollen joints, and persistent disease despite treatment with at least one DMARD. Tofacitinib-treated patients had statistically significant decreases in patient’s global assessment of disease activity compared with placebo-treated patients (P<0.0001).¹¹ The anticipated Prescription Drug User Fee Act (PDUFA) date is August 2012. Tofacitinib has also been submitted for approval in Japan.

Drug Approvals

Glucarpidase (Voraxaze) has been FDA approved as a treatment for the rapid and sustained reduction of toxic MTX levels due to impaired renal function.¹² If patients have impaired renal function or their renal function becomes impaired, they may be at increased risk of MTX toxicity. This mostly occurs in oncology patients, but since MTX is used for autoimmune diseases, these patients may also benefit from this treatment. Glucarpidase is a recombinant enzyme that rapidly lowers serum MTX levels to below the toxicity threshold to prevent renal and hepatic damage, as well as aphthous ulcers, intestinal lining damage, skin rashes, and low blood counts. It is administered intravenously and has been granted orphan drug status in the U.S. and the European Union.