VANCOUVER – Oral tofacitinib for adults with moderate to severe plaque psoriasis demonstrated sustained efficacy and a “generally manageable” safety profile throughout 2 years of follow-up in a large, multicenter ongoing long-term extension study, Dr. Matthias Augustin reported at the World Congress of Dermatology.
One month after enrolling in the phase III, open-label trial (known as OPT Extend), and going on the investigational oral Janus kinase inhibitor at 10 mg b.i.d., 56.2% of the 2,847 participants showed a PASI 75 response – that is, at least a 75% reduction from their baseline Psoriasis Area and Severity Index score. After 2 years in the OPT Extend study, 64.5% of the 1,912 patients remaining in the study were PASI 75 responders.
Similarly, 56.3% of patients went from moderate or severe disease at baseline to “clear” or “almost clear” by Physician Global Assessment (PGA) at 1 month, and 53.9% of participants had a PGA score of 0 or 1 at 24 months, added Dr. Augustin, professor of dermatology at the University of Hamburg-Eppendorf and director of the German Center for Health Services Research in Dermatology and Nursing.
Psoriasis patients who had participated in any of four earlier phase III or two phase II randomized, controlled trials of tofacitinib were eligible to participate in OPT Extend. Participants were placed on tofacitinib at 10 mg b.i.d. for the first 2 months of the open-label study; then investigators adjusted their dose individually – either 5 or 10 mg b.i.d. – at each follow-up visit based on efficacy and side effects. For purposes of OPT Extend, patients’ baseline PASI and PGA scores were defined as the values recorded on the day they were randomized in the earlier round of trials.
Through 2 years of follow-up in this interim analysis of OPT Extend, less than 10% of subjects discontinued tofacitinib because of adverse events. The adverse events were the same as the ones that arose in the earlier, briefer randomized trials, the longest of which lasted 1 year. No signs of cumulative organ toxicity were evident during the additional follow-up.
Slightly more than 4% of all adverse events were categorized as severe, while 62% were mild. The most frequent adverse events were nasopharyngitis in 16% of patients, increased creatinine phosphokinase in 10%, and upper respiratory tract infections in 7%. Serious infections requiring systemic antibiotics or hospitalization occurred in 1.8% of patients on tofacitinib for 2 years, the most common of which were pneumonia, herpes zoster, and urinary tract infection. Herpes zoster occurred in 3.5% of participants, with most cases being mild or moderate. Malignancies other than nonmelanoma skin cancers occurred in 1.2% of subjects.
In terms of laboratory findings of interest, patients’ LDL/HDL ratio remained stable throughout 24 months on tofacitinib. Nor were there any clinically meaningful changes in average levels of other laboratory parameters, including hemoglobin, creatinine phosphokinase, lymphocytes, and neutrophils. A lymphocyte count below 500/mm3 occurred in 0.4% of patients at some point; however, it was unrelated to duration of exposure to tofacitinib and wasn’t linked to an increased infection rate.
Dr. Augustin said an unmet need exists for effective and nontoxic oral medications for moderate to severe psoriasis, because many patients would prefer not to take an injectable biologic. Tofacitinib is aimed at filling that need, and serving as an easier, less toxic initial therapy. However, it is essential that an optimal oral agent have a favorable safety profile because psoriasis is a lifelong disease with an average lifetime duration in excess of 40 years in adults and more than 60 years in affected children, he said.
Pfizer, which is developing the drug, has filed for marketing approval for tofacitinib for treatment of adults with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. The Food and Drug Administration has announced its intent to issue a ruling on the application in October 2015.
The OPT Expect study is funded by Pfizer. Dr. Augustin is an adviser to and/or a recipient of research grants from Pfizer and more than a dozen other medical companies.