UPDATED: 06/21/2012
BERLIN – If the Food and Drug Administration follows the advice of its Arthritis Advisory Committee and approves tofacitinib as a new drug for treating rheumatoid arthritis later this summer, the oral, small-molecule drug may start to muscle in on the treatment turf now occupied by antitumor necrosis factor drugs, some experts predicted at the Annual European Congress of Rheumatology.
The attraction would be the good efficacy tofacitinib has shown in five phase III trials, a decent safety profile that looks on par with antitumor necrosis factor (TNF) drugs, and delivery as a twice-daily oral pill, a property that will give tofacitinib an edge over the anti-TNFs and other biologics that require injection or infusion.
Dr. Joel M. Kremer
"The fact that [tofacitinib] is oral is something of an advantage, so there will be a role for it, and it makes sense therapeutically," Dr. Joel M. Kremer said at the meeting. "But we will need to be smart" on using tofacitinib and other new drugs from the same class to treat patients with rheumatoid arthritis (RA), and their use relative to methotrexate and the biologics, said Dr. Kremer, a rheumatologist and professor of medicine at Albany (N.Y.) Medical College.
Another view was that tofacitinib will need to prove its value in larger numbers of patients, and though it will be a welcome new option – first to market from the class of Janus kinase (JAK) inhibitors – it will take its initial place post approval behind the anti-TNFs, which have more than a decade’s track record, said Dr. Iain B. McInnes in a separate talk at the meeting. Many rheumatologists "feel they will kick in after a first biologic treatment," which itself comes after first-line methotrexate, said Dr. McInnes, a rheumatologist and professor and Muirhead Chair of Medicine at the University of Glasgow, Scotland.
"The efficacy we’ve seen [from tofacitinib and other JAK inhibitors] is very encouraging, but safety will be a major driver of clinical decisions and [will] influence the order of choice. If a patient does not get an adequate response from methotrexate after 3-6 months, I would add a biologic drug, especially an anti-TNF. Inevitably, there will be less safety assurance with the new drugs. The current role for JAK inhibitors is closer to the options like abatacept, rituximab, and tocilizumab, but I think that may change" once JAK inhibitors enter routine practice, Dr. McInnes said in his talk.
Dr. Roy Fleischmann
"I have a lot of experience with tofacitinib, and I’m very comfortable with it; if a patient wanted this drug, I would use it," said Dr. Roy Fleischmann, who led phase II and phase III trials with tofacitinib and is codirector of rheumatology at Texas Health Presbyterian Medical Center in Dallas.
"What will practicing rheumatologists with no experience with the drug do? We’ll see what the FDA says. They might use it after methotrexate, because the data are strong. It will be up to patients: an oral drug or an injected one."
Pfizer, the company developing tofacitinib, reported data from five phase III trials and safety experience in about 4,800 patients to the FDA Advisory Committee in May. And four of the five trials examined use of the drug in RA patients as monotherapy; in combination with methotrexate; in combination with background methotrexate in patients who failed to respond to an anti-TNF drug; and in combination with a background disease modifying antirheumatic drug. The fifth study, a 2-year trial that so far has reported results from an interim, 1-year analysis only, examined tofacitinib’s ability when used in combination with methotrexate to stop radiographic progression of joint damage, compared with methotrexate alone.
Results from across the studies showed consistent efficacy, including inhibition of radiographic progression that significantly surpassed placebo patients, and a "consistent side effect profile," Dr. Kremer said. "I consider it on the same shelf for potential infections and adverse events as the [already approved] biologics," he said in an interview. He said he would shy away from prescribing tofacitinib, or any biologic, to patients who get frequent pneumonia, cellulitis, or other infections.
Perceived safety will likely be the major driver – or impediment – for use of tofacitinib during the first year or 2 after its approval, predicted Madhuri Borde, Ph.D., director of the immune and inflammatory disorders group of Decision Resources, a pharmaceutical-market consulting company in Burlington, Mass. In mid-May, Dr. Borde presented 52 U.S. rheumatologists with active RA practices the same tofacitinib data that the FDA Advisory Committee saw and she asked the rheumatologists what they thought of the drug and how they might use it soon after it hit the U.S. market.*