medwireNews: Background glucocorticoid use does not significantly affect the vast majority of efficacy and safety outcomes in clinical trials of tocilizumab, adalimumab, or methotrexate monotherapy in patients with rheumatoid arthritis (RA), research suggests.
Among the four randomized controlled trials (RCTs) studied (AMBITION, ACT-RAY, ADACTA, and FUNCTION), Mary Safy-Khan (UMC Utrecht, the Netherlands) and colleagues found just one exception to this conclusion: glucocorticoid users in a methotrexate trial arm had less radiographic progression than non-users.
They therefore believe: “Researchers do not have to regard inclusion of patients with RA on background [glucocorticoids] use as a major bias in clinical trials when investigating efficacy and safety of tocilizumab, adalimumab or methotrexate.”
The study included data for 1750 patients with RA, of whom 818 were glucocorticoid users taking a stable dose for at least 4–6 weeks prior to randomization and throughout the first 24 weeks of the trial. Across the four trials, the mean baseline glucocorticoid dose was 6.4–7.5 mg/day prednisone equivalents.
The researchers report in the Annals of the Rheumatic Diseases that, at week 24, there was no significant difference in change in CDAI from baseline between glucocorticoid users and non-users in the tocilizumab monotherapy arms of the AMBITION, ACT-RAY, ADACTA, and FUNCTION trials, with adjusted mean differences of –1.4, 1.2, –4.2, and 0.8, respectively.
For adalimumab monotherapy, the mean difference in CDAI change between glucocorticoid users and non-users was a nonsignificant 4.3 points in the ADACTA trial, while nonsignificant mean differences of –0.9 and –1.7 were observed for methotrexate monotherapy in the AMBITION and FUNCTION trials, respectively.
There were also no significant differences between glucocorticoid users and non-users in CDAI remission rates, ACR50 response rates, patient-reported outcomes, or serious adverse event rates for any of the treatment groups.
In their analysis of radiographic progression, Safy-Khan and team found no significant difference between glucocorticoid users and non-users undergoing treatment with tocilizumab in the FUNCTION and ACT-RAY trials at weeks 52 and 104.
However, they did find that glucocorticoid users receiving methotrexate in the FUNCTION trial had significantly less radiographic progression than non-users at weeks 52 and 104, with adjusted mean differences in the change from baseline of −1.16 and −1.60, respectively.
In spite of this, Safy-Khan et al conclude that their findings “support inclusion of patients with RA, who are on a low-moderate and stable [glucocorticoid] dose, in RCTs, as is common practice.”
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