Lack of effectiveness and adverse reactions are the common reasons for quitting treatment, but there are variations among drugs Trialling another TNF inhibitor in rheumatoid arthritis patients who stopped a first TNFi within six months because it wasn’t effective is unlikely to be successful, according to new Australian research. On average, patients who discontinued their […]
Lack of effectiveness and adverse reactions are the common reasons for quitting treatment, but there are variations among drugs
Trialling another TNF inhibitor in rheumatoid arthritis patients who stopped a first TNFi within six months because it wasn’t effective is unlikely to be successful, according to new Australian research.
On average, patients who discontinued their TNFi treatment because of ineffectiveness only lasted nine months on a second TNFi before quitting again, compared with up to four years for patients who commenced on another class of drugs, such as rituximab, instead.
Presenting his findings at the EULAR conference in Amsterdam, Sydney rheumatologist Professor Peter Youssef explained that persisting with TNFis in patients who had shown little benefit early (within six months) on was commonplace in Australia, occurring in 41% of patients.
“TNFis have been around for a long time,” the clinical professor at the University of Sydney said.
“We know the risks and the benefits, and I think we’re very conservative as rheumatologists, so we tend to try and stick to drugs that we know well.”
However, this real-world analysis of data from 37 rheumatology practices, and almost 90 rheumatologists, sheds light on how commonly patients quit their first-line biological or targeted synthetic DMARD because of a lack of efficacy.
Importantly, it also shows the effectiveness and discontinuation rates of different second-line treatments among these patients who had had their disease for an average of 10 years.
The primary failure rate found in the study was lower than that found in other studies, according to Professor Youssef and his team.
In the 7000-patient cohort, with an average age of 61, two out of five stopped taking their first-line biologic or targeted synthetic DMARD, and of these, only one in three did so within the first six months of starting the treatment.
When researchers looked at the reasons given for discontinuing treatment, the most common were lack of effectiveness and adverse reactions.
However, there was variation among drugs. Almost half of all patients who stopped taking tofacitinib did so early, and on the other end of the spectrum, only 17% of those who stopped tocilizumab did so within the first six months.
In addition, if patients had initially been given an TNFi, and failed early and were then started on another TNFi, the chances of successful treatment were low, “suggesting the disease was driven by another mechanism”, Professor Youssef said.
The study showed, among these patients, using DMARDs such as tocilizumab and rituximab as a second-line treatment was more successful, with 78% and 75% of patients still taking them at six and 12 months, respectively.
Professor Youssef, a physician at the Royal Prince Alfred Hospital, Sydney, said the best results for patients failing first-line treatment were in changing classes.
But he explained patients who initially responded to a TNFi but then developed secondary failure should be considered differently.
At the moment, much of the research supported staying in the same class among patients with a secondary failure, after having already responded to a TNFi, he said.
“There’s some biological basis to [replacing one TNFi with another in these patients],” he said.
“If you are on, say, adalimumab and you develop antibodies to adalimumab, you might then go onto etanercept and you might do well on that because your inefficacy has been due to antibodies from the drug.”
“But rather than just look at whether patients failed the drug [clinicians should look at] when they failed it. Was it early on, or was it later?”
The study, which was sponsored by Roche Products, analysed data on abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab and tocilizumab, rituximab and tofacitinib.
