SAN FRANCISCO – Sulfasalazine prevents formation of antibodies against tumor necrosis factor inhibitors, but probably not as well as methotrexate, according to a European study of 140 axial spondyloarthritis patients.
“The effect of sulfasalazine on the development of antidrug antibodies has not been studied before. Our initial hypothesis was that methotrexate would [reduce] antibody formation” because it’s been shown to do that before, but that “sulfasalazine would not. This was a surprise to us,” said senior investigator Dr. Alejandro Balsa, chief of rheumatology at La Paz University Hospital in Madrid.
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Medicine vial of methotrexate, made by APP Pharmaceuticals. Vial is partially full.
The findings suggest that sulfasalazine, like methotrexate, might “prevent immunogenicity and, hence ... secondary failure of” a tumor necrosis factor inhibitor (TNFi), he said at the annual meeting of the American College of Rheumatology.
Thirty-one patients (22%) were on infliximab (Remicade) and 109 (78%) were on adalimumab (Humira) in the year-long study, which was conducted in Madrid and Amsterdam.
Of the 90 patients on TNFi monotherapy, 33 (37%) developed TNFi antibodies, including 3 of 13 (23%) on infliximab monotherapy and 30 of 77 (39%) on adalimumab alone. The difference was not statistically significant.
Of the 50 patients on concomitant therapy, antibodies against anti-TNF agents occurred in 6 of 35 on sulfasalazine (17%), including three cases on infliximab and three on adalimumab. There was just one antibody case in 15 patients on methotrexate (7%); the patient was on adalimumab.
The trend toward better antibody protection with methotrexate was, again, not significant, probably because of the small numbers in the study.
Methotrexate and sulfasalazine are not routinely prescribed for axial spondyloarthritis; patients were on them in the study to help with peripheral manifestations. The drugs only prevent antibodies if started before a TNFi. “Once patients develop anti-[TNF] antibodies,” it’s too late, Dr. Balsa noted.
Despite the promising results, he said there’s not enough data at this point to recommend routine pretreatment with methotrexate or sulfasalazine to prevent TNFi antibodies.
As expected, antibodies diminished the clinical effect of a TNFi. Less than a quarter of antibody patients, versus more than a half free from antibodies, reached the investigators’ mark for low disease activity at 1 year: clinical improvement plus a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score below 4 and normal C-reactive protein (P = .03).
Also at 1 year, patients on monotherapy had an overall BASDAI improvement of about 1 point on the 10-point scale. Patients on methotrexate gained an additional point or so (P = .04), while those on sulfasalazine gained about a half point extra (P = .16).
“We only saw significant improvements in patients treated with methotrexate, probably because 100% cotreated with methotrexate had free” serum TNFi “at 1 year, as compared with only 82% cotreated with sulfasalazine,” Dr. Balsa said.
Oddly, the investigators detected free serum TNFi at 1 year in 78 (87%) monotherapy patients, which was more than in those cotreated with sulfasalazine; he didn’t address the finding.
The mean BASDAI at baseline was 6. Ankylosing spondylitis was the most common diagnosis in the study. More than half the subjects were men, the majority of patients were HLA-B27 positive, and their mean disease duration was 11 years.
Dr. Balsa’s institution receives research funding from Pfizer, UCB, and Roche, and he receives speakers fees from those companies plus AbbVie, Merck, and Bristol-Myers Squibb. Other investigators disclosed financial ties to those or other companies.