Rheumatoid arthritis

Window of opportunity for anti-TNF in early inflammatory arthritis

Three quarters of patients with early inflammatory arthritis who respond to a combination of infliximab and methotrexate can expect to have a second drug-free year in remission, according to European research.

The Definitive Intervention in New Onset Rheumatoid Arthritis (DINORA) trial randomised 90 patients with synovial swelling in at least two joints for two to 12 weeks duration to either the combination of infliximab and methotrexate, methotrexate monotherapy or placebo.

Supportive therapy including NSAIDS and up to 10 mg/day prednisone or similar were also permitted in each group.

Sustained clinical remission at 12 months was achieved in 32%, 14% and 0% of patients in the three arms respectively and treatment was ceased at 54 weeks.

Subsequently remission was maintained despite no therapy in 75% of the patients who had received the combination therapy compared to only 20% of the patients who received methotrexate only.

The number needed to treat with infliximab plus methotrexate for sustained remission at two years was two compared to either methotrexate alone or placebo.

The study also found the vast majority of patients who went on to achieve drug-free remission, attained remission within the first 30 weeks of treatment.

“Together, these findings suggest that once joint inflammation is clinically manifest, symptomatic therapy does not impact on the course of disease, that initiation of DMARD therapy is warranted to improve outcomes, and that early intensive treatment with anti-TNF + MTX leads to drug-free remission in 1 of 4 patients.”

The study provides some support for the window of opportunity hypothesis – that a short period of intensive therapy early in the disease course may reverse the disease process and produce long-term benefits.

However the fact that two thirds of patients did not attain remission in the first year was disappointing, the study authors said.

Commenting on the results, Dr Mihir Wechalekar, a rheumatologist at Flinders University and Flinders Medical Centre, agreed a higher remission rate might have been expected.

“The study is significant as it shows that the disease trajectory in early inflammatory arthritis can be modified significantly by early aggressive combination treatment,” he told the limbic.

The significant number of non-responders raised the possibility of either a heterogeneous cohort or underlying patho-biological heterogeneity, Dr Wechalekar added.

And there may be difficulties with extrapolating the findings to clinical practice, he suggested.

“Although in Australia we are unable to access TNF inhibitors for early disease like that described in the study, it is difficult to extrapolate these findings to a patient with early RA as a significant proportion did not fulfil RA classification criteria and less than a third of those who did achieved remission even with the combination therapy.”

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