In an abstract of pooled studies presented at the recent 2012 ACR/ARHP Annual Meeting in Washington D.C., tofacitinib, the new oral janus kinase inhibitor, appeared to have efficacy in the treatment of rheumatoid arthritis (RA) patients with disease refractory to tumor necrosis factor–alpha (TNF) inhibitors.7 ACR20 responses for patients who failed one TNF inhibitor occurred in 44% and 50% of patients, respectively, receiving 5 mg tofacitinib twice daily (BID) and 10 mg BID, versus 24% of placebo-treated patients (P<0.0001). For patients who failed two TNF inhibitors, 41% of tofacitinib 5-mg BID-treated patients and 53% tofacitinib 10-mg BID-treated patients were ACR20 responders, versus 16% of placebo patients (P<0.01 for 5 mg; P<0.0001 for 10 mg).
Drug Safety
Methotrexate/Proton Pump Inhibitors
On October 30, 2012, the FDA approved supplemental information on the pharmacokinetics of using milnacipran (Savella) in lactating women.8 The data reported that milnacipran is present in the milk of lactating women treated with the agent. Lactating women (n=8) who were at least 12 weeks postpartum and were weaning their infants received a single, oral dose of 50 mg milnacipran. The maximum estimated daily infant dose for milnacipran from breast milk was 5% of the maternal dose based on peak plasma concentrations. In most patients, peak concentrations of milnacipran in breast milk were seen within four hours after the maternal dose. Based on this data, the product information was updated to recommend that due to the limited amount of data regarding infant exposure to milnacipran, it should be used cautiously in nursing women.
In October 2012, the FDA updated the Warnings and Precautions section of the label for tocilizumab (Actemra) related to hypersensitivity reactions, including anaphylaxis.9 Postmarketing, clinically significant hypersensitivity, and anaphylaxis reactions have occurred both with and without previous hypersensitivity reactions in patients treated with the agent. Reactions have occurred in patients receiving a range of doses, and in some cases, this has occurred with the first tocilizumab infusion. Some of these reactions have led to fatalities, and events even have occurred in patients who were premedicated. If anaphylaxis or other clinically significant hypersensitivity reaction occurs, administration of tocilizumab should be stopped immediately, and tocilizumab should be permanently discontinued.10
There is accumulating evidence suggesting that combined use of methotrexate (MTX; at both low and high doses) and proton pump inhibitors (PPIs) may reduce the clearance of MTX, leading to elevated and prolonged serum MTX levels, and/or levels of its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities.11 Implicated PPIs include omeprazole, esomeprazole, and pantoprazole, but other PPIs may also cause this same interaction (e.g., a class effect) because this interaction has been described for different PPIs. PPIs are often used in patients with RA to reduce nonsteroidal antiinflammatory–associated gastric ulcers, to treat gastric ulcers and manage gastroesophageal reflux disease, as well as to manage gastrointestinal side effects of MTX.
