Tofacitinib is making its way

The FDA panel voted 8-2 inn favour of tofacitinib, which will be approved the as first drug of a new class (small molecules), an oral drug to treat adult patients with moderate to severe rheumatoid arthritis.
There’s a good article on tofacitinib on Wikipedia: http://en.wikipedia.org/wiki/Tofacitinib. “A Brief History of Tofacitinib” on Forbes is rather industry friendly: http://www.forbes.com/sites/johnlamattina/2012/05/10/a-brief-history-of-tofacitinib/. @dsymons has supplied the following link on the advisory panel’s voting: http://www.emaxhealth.com/11306/new-arthritis-drug-tofacitinib-may-be-available-soon.
There has been agreement that there is sufficient evidence of the efficacy of tofacitinib for the treatment of moderately to severely active rheumatoid arthritis. Some of the data is already in my blog entry about EULAR11 “New kids on the block”: http://rheumatologe.blogspot.de/2011/11/tofacitinib-oral-janus-kinase-inhibitor.html. After ACR2011 I had put on my blog all the conclusion of the abstracts concerning tofacitinib: http://rheumatologe.blogspot.de/2011/11/tofacitinib-oral-janus-kinase-inhibitor.html.
The radiographic data on stopping disease activity weren’t convincing, as only 2 of the 10 panel members voted in favour. One of the two has been mentioned, Leslie Crofford, MD, from the University of Kentucky School of Medicine in Lexington. I’ve been listening to her talks on various subjects at different meetings (ACR, EULAR, and the Fibromyalgia Symposium in Germany) since the mid 90ies. I think she sometimes talks too close to meet the needs of pharmaceutical firms (I remember a very emotional pro for coxibes).
As the dosages of tofacitinib were nearly equal in efficacy, the panel rather voted for 5 mg taken twice per day. There were safety concerns – the higher the dose and the longer the treatment lasted the higher the ratio of Adverse and severe adverse events; increases in malignancy rates and serious infection rates are indeed alarming. There were also increases in lipid and cholesterol levels (like tocilizumab). And you might see neutropenia (also like tocilizumab).
I don’t think that the risk profile is so bad that tofacitinib shouldn’t get FDA approval. I’d rather prescribe it to patients with severe disease, who already had been treated sufficiently with DMARDs and biologics, but had disease progression despite these drugs or secondary failure. I might also consider it in patients, who have such bad veins, which make intravenous therapies a torture both to patient and physician; but … tocilizumab will get subcutaneous approval soon.
All in all I see potential for tofacitinib, but initiation would be with great caution. Tofacitinib is making its way, but where to is still open for discussion.

Thanks Dana for stimulating me to write this blog entry.