"We don’t usually have the opportunity to hear the data for generic drugs" as much as for brand-name formulations, Dr. Kremer said in an interview. "Will data like this substantially change prescribing patterns? Probably not, but what might happen is that insurers may look at these data and say that patients should fail triple therapy before starting a biologic. That would be a sea change" for rheumatology, he added.
"I have always used methotrexate first, usually in combination with hydroxychloroquine," Dr. Kremer said. He has not usually also prescribed sulfasalazine, but said he would consider adding it based on the new data.
The new study enrolled patients with a DAS28 score of 4.4 or higher despite at least 12 weeks of stable methotrexate therapy with a weekly dosage of 15-25 mg. The patients averaged about 57 years old. After the first 24 weeks on randomized treatment, patients who did not have a decrease in their DAS28 of at least 1.2 units switched to the alternate regimens. The primary outcome was change in DAS28 at week 48 according to initial treatment assignment; the researchers collected 48-week DAS28 scores from 309 enrolled patients. The mean change in DAS28 from baseline at 48 weeks was a 2.12-unit reduction in the triple-therapy patients and a 2.29-unit reduction in the etanercept patients, an average 0.17-unit difference between the two treatment arms that was not statistically significant and that fell within the study’s prespecified range for noninferiority for triple therapy.
A similar percentage of patients, 27%, in each of the treatment arms switched to the alternate therapy at 24 weeks due to lack of an adequate initial response. There were also no statistically significant differences between the treatment arms in their rate of American College of Rheumatology (ACR) 20 and 50 responses at both 24 and 48 weeks.
Dr. Edward C. Keystone
The results showed significant differences between the treatment arms after the first 24 weeks of treatment for higher-level responses. For example, the percentage of patients achieving an ACR 70 response was 5% in the triple-therapy patients and 16% in the etanercept patients, a statistically significant difference. The rate of patients with a DAS28 score of 2.6 points or less at 24 weeks was 13% in the triple-therapy patients and 22% in those on etanercept, a significant difference.
Based on findings like these, "I would start a biologic in a patient who failed high-dose methotrexate and had poor prognostic factors and highly active disease, because at 6 months etanercept had the edge," said Dr. Edward C. Keystone, director of the Centre for Arthritis and Autoimmune Disease at Mount Sinai Hospital in Toronto, and a coinvestigator on the new study. But for all the other patients, "why not start on triple therapy first if you can switch them later if needed and the patients do well?" he asked. "The important observation is that the same percentage of patients failed in each arm. That is a huge message."
The RACAT study received no commercial support. Dr. O’Dell said that he had no disclosures. Dr. Furst has been a consultant to or received grant support from Abbott, Amgen, Bristol-Myers Squibb, and other companies. Dr. Kremer has been a consultant to or received grant support from Pfizer, Abbott, Genentech, and other companies. Dr. Keystone said that he has been a consultant to or has received research grants from Amgen, Pfizer, Merck, and other companies.
mzoler@frontlinemedcom.com On Twitter @mitchelzoler