Rheumatoid arthritis

OPAL reveals variations in persistence with second line RA treatment

Many patients with RA are switched to another TNF inhibitor after first-line TNFi failure, even though second-line TNFi treatment has inferior persistence compared to a switch to non-TNFi treatment, Australian data show.

A retrospective review of RA treatment patterns in 7740 patients in the OPAL dataset between 2010-2017 found that half (49%) of the 6914 patients who received first-line biological or targeted synthetic DMARDs stopped treatment.

Of the 3383 patients who stopped first-line treatment, 1263 (37%) were classified primary failures (stopping within 6 months). The most common reason cited by rheumatologists for stopping treatment was lack of efficacy, in 36% of patients.

The study, led by Professor Peter Youssef of the Royal Prince Alfred Hospital, Sydney, analysed persistence rates in patients who switched to other treatment after stopping first-line TNFi, but not for other agents as the number of patients on other b/tsDMARDs was low.

It found that 43% of the patients who stopped first-line TNFi treatment received second-line TNFi. However, persistence rates were lower for these patients than those who were switched to a second-line non-TNFi treatment.

The study also showed that patients with a primary failure to a TNFi were no less likely to respond to a second TNFi than those who have sustained a secondary failure.

The median times to stopping second line treatment after primary failure of first line TNFi were nine months for TNFi, 11 months for abatacept, 21 months for tofacitinib and tocilizumab and 49 months for rituximab.

After secondary failure of first line TNFi, the median times to stopping second line treatment were 11 months for TNFi, 14 months for abatacept, 17 months for tofacitinib, 24 months for tocilizumab and 39 months for rituximab.

The study investigators said it might be expected that patients with a primary failure to a TNFi would be less likely to respond to a second TNFi rather than another agent with a different mode of action.

They said the real world data from OPAL had confirmed these expectations in a large cohort of patients, and also showed wide variation between individual bDMARDs and tsDMARDS in primary failure rates of first line treatment.

They said it was notable that tofacitinib had the highest primary failure rates (67%) compared to other agents such as certolizumab pegol (43%), golimumab (42%), TNFis (38%), adalimumab and etanercept (36%), abatacept (34%) infliximab/ rituximab (32%) and tocilizumab (20%).

However they cautioned that the data for tofacitinib was not mature as it had only been listed on the PBS in 2015.

“A large proportion of patients who stopped first-line TNFi therapy received another TNFi despite evidence for longer treatment persistence on second-line b/tsDMARDs with a different mode of action,” they concluded.

The study is published in the Journal of Rheumatology and was funded by Roche, makers of tocilizumab.

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