BERLIN – Methotrexate cut the immune response to adalimumab in a dose-dependent way, in a series of 272 consecutive rheumatoid arthritis patients at one Dutch medical center.
A high methotrexate dosage (at least 22.5 mg/week) sliced the rate of antibody production against adalimumab by a statistically significant 86% compared with patients who got no methotrexate, and by a significant 61% compared with patients on low-dose methotrexate (10 mg/week or less), Dr. Charlotte Krieckaert reported at the annual European Congress of Rheumatology.
Mitchel L. Zoler/IMNG Medical Media
Dr. Charlotte Krieckaert
The message from this finding is that RA patients on adalimumab or other biologic drugs that could trigger antibody production should get "as much methotrexate as they can tolerate," ideally about 25 mg/week, according to Dr. Krieckaert, a rheumatology researcher at the Reade Centre for Rehabilitation and Rheumatology in Amsterdam. "The chances of a good response and a maintained response [to a biologic drug] are higher when you also give methotrexate," she said in an interview. "We saw incremental value from methotrexate, and it was most valuable during the first 6 months" on adalimumab. "Maybe we can taper off the methotrexate" after 6 months, but so far this has not been studied.
A prior report by Dr. Krieckaert and her associates documented that patients who produce antibodies against adalimumab have blunted beneficial effects from the treatment and have a lower remission rate (JAMA 2011;305:1460-8).
The problem of an immune response by some RA patients to biologics first appeared with infliximab, an effect that methotrexate also helped reduce. Antibody reactions against adalimumab were identified more recently, commented Dr. Jane Gibson, chief of the Fife (Scotland) Rheumatic Diseases Unit. "I think in 2 or 3 more years, once antibody responses to biologics are routinely measured in practice, you’ll find physicians tailoring the methotrexate dose," finding the minimum weekly dosage of methotrexate that an RA patient needs to prevent an immune response to whatever biologic the patient also takes, Dr. Gibson said in an interview.
The consecutive series that Dr. Krieckaert and her associates review included 272 patients who were begun on adalimumab in an observational cohort. In all, 70 (26%) received no methotrexate, 40 (15%) received a low dose, 54 (20%) got an intermediate dose (12.5-20 mg/week), and 108 (40%) got a high dose. (Percentages do not equal 100% because of rounding.)
During 3 years of follow-up, 76 patients (28%) developed a significant immune response to the adalimumab, accounting for half of those getting no methotrexate, 35% of patients on a low methotrexate dose, 22% on an intermediate dose, and 14% on a high dose.
An odds ratio analysis showed that low-dose methotrexate cut the frequency of immune responses by 64%, an intermediate dose cut the incidence of antibody production by 78%, and high dose cut the rate by 86% compared with no methotrexate, all statistically significant differences. Only high doses of methotrexate significantly cut the rate of antibody production compared with low doses.
Dr. Krieckaert said that she had no disclosures. Dr. Gibson said she had no disclosures.