The living evidence program now spreads to US and Canada.
Rheumatologists have several effective treatment options when a tumour necrosis factor (TNF) inhibitor fails in rheumatoid arthritis, but there is still no convincing evidence that one biologic or targeted synthetic DMARD is superior to another.
That was the conclusion of a new Cochrane living systematic review and network meta-analysis, which evaluated the evidence for advanced disease-modifying antirheumatic drugs (DMARDs) in adults with established rheumatoid arthritis whose disease had not responded adequately to a previous TNF inhibitor.
The review was part of Cochrane’s living evidence program and would be updated as new trials became available, said Melbourne rheumatologist Professor Rachelle Buchbinder AO, an NHMRC investigator fellow, Vice Chancellor’s Distinguished Professor, and head of the Musculoskeletal Health Unit and Wiser Health Care Group at Monash University’s School of Public Health and Preventive Medicine.
She said the evidence already underpinned Australia’s NHMRC-approved living rheumatoid arthritis guidelines and was also informing updated guidelines in Canada and the United States.
“I don’t think anything changes really except our confidence in knowing that how we treat RA in Australia is based upon the best currently available evidence,” the review’s senior author told Rheumatology Republic.
The review included 19 randomised controlled trials involving 4779 patients from North America, Europe, and Asia.
Participants were predominantly women aged 49 to 58 years who had been living with rheumatoid arthritis for between six and 14 years. Nine studies were industry funded and 10 were supported by national research grants.
Researchers found high-certainty evidence that switching to another TNF inhibitor, such as sarilumab, intravenous tocilizumab (4mg/kg and 8mg/kg), intravenous abatacept, rituximab, upadacitinib, tofacitinib, and baricitinib 4mg significantly improved disease activity compared with placebo.
There was also moderate-certainty evidence supporting a switch to subcutaneous abatacept and baricitinib 2mg.
The primary outcome was achievement of an ACR50 response, indicating at least a 50% improvement in disease activity.
Professor Buchbinder said the findings provided reassurance that clinicians have multiple effective options after failure of a first TNF inhibitor.
“This paper was specifically trying to identify which drugs to try after a person with RA had failed a TNF inhibitor,” she told RR.
“We found, based upon 19 trials in people with well-established RA, that there was either high or moderate certainty evidence that they would improve symptoms compared with placebo [regardless of which drug they used].
“We couldn’t really distinguish between them due to lack of enough direct comparisons [most trials compared the active drug to placebo]. And there was significant uncertainty around harms.
“Clinicians can be reassured that for drugs where we have data, they all work reasonably well, so [the choice of which treatment to use] comes down to other factors including patient characteristics, preferences, and values.”
Related
Professor Buchbinder said one clinically useful finding was confirmation that switching to another TNF inhibitor remained a reasonable strategy.
“It possibly won’t change prescribing decisions much. I guess for me it was good to know that it was still worth trying another TNF inhibitor if the first one had failed,” she told RR.
The review also did not identify a preferred biologic or targeted synthetic DMARD for patients requiring a second-line advanced therapy.
“It does not support a ‘best’ b/tsDMARD, so treatment is still about matching the drug to the patient,” Professor Buchbinder said.
She said the findings were highly relevant to Australian rheumatology practice because almost every therapy assessed is already available through the PBS, with sarilumab the only exception despite previous approval by the Pharmaceutical Benefits Advisory Committee.
Importantly, she said, Australia’s PBS prescribing restrictions did not limit clinicians’ ability to apply the evidence.
See the Australian Living Guidelines for Rheumatology here.
