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Anti-TNF-α Efficacy in Trials Not Achieved in Real-World Scenarios


 

Good clinical response and rheumatoid arthritis remission following treatment with tumor necrosis factor-α blockers is much rarer on the community level than results from randomized clinical trials, with their many exclusion criteria, would seem to indicate, according to results from an Italian group of researchers.

The Gruppo Italiano per lo Studio delle Early Arthritis study (GISEA) enrolled 1,257 patients who had longstanding rheumatoid arthritis (RA) and who started therapy with tumor necrosis factor-α (TNF-α) blockers. The original aim of the study was to pinpoint predictors of remission in longstanding arthritis patients treated with TNF-α blockers.

However, in the process, the researchers uncovered an unexpected finding: only 682 (54%) of patients experienced even the minimally acceptable improvement in their symptoms after 6 months of treatment with a TNF-α blocking agent. Specifically, these 682 patients were the only ones to experience at least a 0.25 improvement in their Health Assessment Questionnaire score (HAQ), which is considered the cutoff point for a clinically meaningful response.

Of the patients who dropped out, 32% cited inefficacy and 14% cited adverse events, including skin reactions, infusion reactions, and gastrointestinal problems.

Even at the outpatient clinics, only half of the patients reached a clinically meaningful result as defined by an HAQ improvement of 0.25, wrote the researchers.

“Therefore, patients in clinical practice are not representative of those recruited in clinical trials, and certainly do not reach the outcomes that have been provided in [randomized controlled clinical trials]. Among these, remission was observed in a small percentage of patients with a long disease duration,” they added.

The most likely interpretation for this discrepancy—randomized trials' extensive exclusion criteria—could “seriously influence not only the safety issue in general, but also the final clinical outcomes in aggressive and severe disease at the community level,” the study investigators noted (J. Rheumatol. 2007;34:1670-3).

Of the 682 patients who were studied further, only 591 (47% of the whole cohort) had both a 0.25 improvement in HAQ scores and underwent regular bimonthly assessments of clinical and laboratory measures.

In this cohort of 591 patients, 404 (68%) were women, and the mean age was 53 years.

Overall, 32% of the men and 24% of the women achieved remission, a difference that was statistically significant and which prompted the authors to speculate that “male patients with RA seem to benefit more from anti-TNF-α strategies than do female patients.”

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