A large RA strategy study sheds light on TNF inhibitor versus leflunomide in methotrexate non-responders.
A trial that examined prescribing etanercept at six months instead of leflunomide has provided some valuable insights into treatment strategies for early rheumatoid arthritis.
Among the findings is the suggestion that starting biologics early (at six months) might reduce the need for long-term biologics/JAK inhibitors.
The CareRA2020 trial investigated whether patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt.
The trial evaluated two treat-to-target (T2T) strategies – the first starting with 24 weeks of etanercept, and the second adding leflunomide after initial therapy. The findings were published earlier this month in RMD Open.
As part of the trial, treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS).
Within a time window from week eight until week 32, early insufficient responders (28-joint Disease Activity Score – C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks).
Additional treatment adaptations followed the T2T principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP < 2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups.
And while the CareRA2020 trial did not find one T2T strategy superior to the other in terms of long-term disease control, it did highlight differences in the rapidity of achieving remission and the need for tailored approaches for subgroups of patients.
“Half of the patients responded well to initial COBRA-Slim induction therapy,” the authors concluded.
“In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104.”
The authors said continued research would be crucial in optimising treatment strategies and addressing the needs of patients with more difficult-to-manage RA.
“The CareRA2020 trial did not completely solve the unmet need of patients responding insufficiently to conventional initial therapy for early RA, but it provides opportunities to further optimise the treatment approach in this population, for instance, by focussing on the identification of potential subgroups with different disease activity trajectories within the early insufficient responder group,” they wrote.
“A three-year follow-up extension study is currently ongoing, which will hopefully give us more insight on the long term, including cost-effectiveness data.”
Dr Navkiran Sidhu, a consultant rheumatologist at RheumatologySA, with a special interest in complex conditions, including inflammatory arthritis, said that while she did not think the findings were “at that point where it’s changing practice just yet”, the paper raised some interesting points.
“I think it’s early, but one of the things that I think I do kind of agree with was that we should be using biologics earlier, and that might be a good thing longer term, in terms that it might reduce the need to use them for longer,” she told Rheumatology Republic.
“And the second take home would be that treat to target. Really push your patients to have good control, no matter how you do it, but get them there.”
Dr Sidhu said treating RA early had other challenges in Australia that needed to be addressed beyond just which drug therapies to use.
“I think there is a delay in access to rheumatologists,” she said.
“I think there is a delay in recognition in primary care settings, especially in seronegative disease, and just accessing private or public rheumatology is challenging.
“I think having more rheumatologists would definitely help to get people in earlier and increasing awareness with our GP colleagues and primary care physicians would also help.”
Dr Sidhu said GPs needed more education to help them support their patients on biologic therapy.
“I don’t think there’s enough education around how to approach biologics or even synthetic DMARDs. I think there’s a lot of fear around that,” she said.
“GPs are very overworked and overburdened, and already have to know so much without adding this. But there’s a lot, a lot that that could be done that perhaps isn’t being done.”
