medwireNews: The addition of high-dose glucocorticoids to first-line adalimumab and methotrexate in the treatment of rheumatoid arthritis (RA) fails to further improve efficacy, results of a phase IV study show.
Lead researcher Roberto Caporali (IRCCS San Matteo, Pavia, Italy) told medwireNews that he was very surprised by the findings.
“I really was convinced that this aggressive treatment from the beginning would give a higher rate of remission; this was not the case,” he said.
The researchers analyzed outcomes in 106 RA patients randomly assigned to receive intensive treatment with oral prednisone 50 mg/day, which was progressively tapered to 6.25 mg and stopped at 6 months, in addition to adalimumab for 12 months and weekly methotrexate to the end of the 24-month study.
These patients were compared with 112 RA patients with similar baseline characteristics who received standard treatment with placebo instead of prednisone.
The patients had active RA, with disease duration of 1 year or less, and had not previously taken methotrexate or glucocorticoids. All the patients had at least one predictor of aggressive disease.
At 12 months, 6 months after discontinuation of glucocorticoids or placebo, 60% of patients were in remission overall, according to a Disease Activity Score at 28 joints based on C-reactive protein (DAS28-CRP) of below 2.6, while the remission rate was 48% for both a Simple Disease Activity Index (SDAI) score of 3.3 or below and a Clinical Disease Activity Index (CDAI) score of 2.8 or below.
When the standard and intensive treatment groups were compared, there was a significant difference in the rate of DAS28-CRP remission in favor of the standard treatment regimen, at 67.8% versus 52.8% with the intensive treatment regimen. Remission according to SDAI also showed a significant difference in favor of the standard treatment, at 53.6% versus 42.4%, while there was no significant difference in rates of CDAI remission.
“So the aggressive treatment was not related to a higher rate of remission after 1 year of treatment,” Caporali emphasized at the Annual European Congress of Rheumatology (EULAR) 2017.
At 24 months, after stopping adalimumab at 12 months in patients who were in remission, about 40.0% of the patients had flared and only 37.9% were still in remission.
Both groups achieved considerable clinical improvement, as measured by 20%, 50%, and 70% improvement in ACR score over 4, 8, 12, and 24 months, and the response curves were very similar between the intensive and standard treatments. The same was true for the Health Assessment Questionnaire score at each time point.
The frequency of adverse events in the patients who completed the trial was comparable between the two treatment groups, but the rate of patients who discontinued due to adverse events was higher in the intensive than the standard treatment group, at 16.52% versus 9.32%.
“My conclusions are that the addition of high-dose glucocorticoid to a first-line treatment with adalimumab and methotrexate in rheumatoid arthritis patients naïve for methotrexate and glucocorticoids did not prove to induce a further improvement in efficacy and in particular a higher rate of remission after 1 year,” said Caporali.
He added that although the results should be tested and confirmed with other biologic drugs, the high dropout rate due to adverse events in the intensive treatment group should be “carefully considered in the risk–benefit ratio.”
Caporali finished by saying that “a discontinuation of adalimumab in patients achieving remission after 12 months and with negative prognostic factors resulted in a disease flare in more than 40% of patients, regardless of the initial treatment, with or without high-dose glucocorticoids.”
His next steps are to investigate the effects of early low-dose glucocorticoids, which he thinks “would be useful for patients,” but for now treating with tumor necrosis factor inhibitors is probably enough and he recommends they be used from the beginning in RA patients with negative prognostic factors.
By Lucy Piper
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