There are some key differences between EULAR vs ACR recommendations for RA. Plus abatacept to prevent RA progression in at-risk patients and secukinumab promise in GCA.
Rheumatology Republic editor Dr Irwin Lim on EULAR vs ACR recommendations for RA; abatacept to prevent RA progression in at-risk patients; and secukinumab promise in GCA.
RA recommendations: EULAR vs ACR
The updated EULAR recommendations on the management of rheumatoid arthritis were presented by Josef Smolen in the EULAR Recommendations session on Wednesday 1 June.
I thought it was interesting to contrast two key points with the 2021 ACR recommendations.
Recommendation 6
The ACR guidelines provided methotrexate the prominent, monotherapy role as the initial single agent for patients with moderate to high disease activity. The guidelines also recommended that we should really try to avoid routinely prescribing concomitant glucocorticoids given the toxicity of steroid use we all deal with, and the difficulty in tapering steroids in some patients.
Europeans with their COBRA heritage like steroid use more than the Americans.
Did they agree with the ACR guidance on the issue of steroid use?
Professor Smolen highlighted that there was very low to moderate evidence for this ACR guidance.
EULAR chose to continue to recommend the combination of glucocorticoids with methotrexate after another careful literature review.
It’s a pragmatic stance and one my own practice is aligned with. Steroids aid short-term control of disease especially when you have a patient in front of you who clearly has very active RA and is struggling to cope.
There is, however, an important inclusion in the statement, highlighting that steroid use should be tapered, and discontinued, as rapidly as clinically feasible. I am sure we all agree with this.
Recommendation 8
The ACR recommended addition of a bDMARD or tsDMARD versus sulfasalazine and hydroxychloroquine for patients with an inadequate response to methotrexate monotherapy, while accepting that triple therapy may be preferred in situations where there are lower resources. Based on the timing of the ACR guidelines, there was not a recommendation for a bDMARD versus a tsDMARD.
With the ORAL Surveillance data now available, EULAR has changed its own 2019 statement from: “if the treatment target is not achieved with the first csDMARD strategy, when poor prognostic factors are present, a bDMARD or a tsDMARD should be added”, to: “if the treatment target is not achieved with the first csDMARD strategy, when poor prognostic factors are present, a bDMARD should be added; JAK-inhibitors may be considered, but pertinent risk factors must be taken into account.”
So, biologics are favoured over JAK inhibitors.
While this blanket statement for all JAK inhibitors is problematic, I do think my own practice and probably your practice has changed since ORAL Surveillance. The tweak in wording does seem reasonable.
- Update of the EULAR Recommendations on the management of Rheumatoid Arthritis (EULAR Recommendations session)
Abatacept effective in preventing progression to RA
I’m sure we’d like to delay or prevent the onset of rheumatoid arthritis (RA) in those who seem at high risk of it.
ARIAA (POS0531) is a multi-national, randomised double-blinded, placebo-controlled study trying to improve our understanding of whether this is possible.
Between 2014 and 2019, 100 RA-at risk patients, who were both ACPA-positive and showing MRI signs of inflammation, were randomised to receive either abatacept or placebo for 6 months only.
After this 6-month treatment phase, the primary endpoint was reached: 61% of the abatacept group improved in MRI parameters (synovitis, tenosynovitis, and osteitis) compared to only 31% in the placebo group. In addition, 17 patients in the placebo group (34.7%) progressed to RA versus only 4 patients (8.2%) in the abatacept group (p= 0.0025).
We already knew this data from ACR 2021. So, what happens after abatacept is stopped?
The impressive news is that there is an effect even one year after the relatively brief intervention.
At 18 months after inclusion into ARIAA, the number of patients who progressed to RA was lower in the abatacept group (35%) than in the placebo group (57%; p=0.0421).
The conclusion: abatacept significantly reduces subclinical joint inflammation and delays the development of RA in at-risk individuals.
I’m quite optimistic about this data. Our older biological DMARDs should keep getting cheaper and it is likely to make more and more sense, including health-economically, to use them earlier, especially if we may get by with short, defined courses actually providing longer-term benefit.
- POS0531 Abatacept delays the development of RA – clinical results after 18 months from the randomized, placebo-controlled ARIAA study in RA-at risk patients.
TitAIN trial – secukinumab for GCA
Cool trial name, good result for secukinumab, and we have another reason to be optimistic about giant cell arteritis (GCA).
At the ACR Convergence 2021 virtual meeting, we were introduced to this phase 2 trial of secukinumab in GCA. I was looking forward to hearing new data and, having just sat through the oral presentation (Abstract OP0182), it seems like a rehash of what was presented previously.
However, it’s good stuff so I’ll summarise.
Tocilizumab has been a game changer for us in GCA but there is still an unmet need. Hence, TitAIN, the first randomised, parallel-group, double-blind, multi-centre, placebo-controlled trial of secukinumab in people with GCA. Participants were aged 50 and over, with new onset or relapsing GCA. They had to be bDMARD naive.
There were 27 patients in the secukinumab 300mg arm (with typical subcutaneous dosing) while 25 entered the placebo arm (yes, small numbers). Prednisone taper occurred over 26 weeks.
The primary endpoint was met easily. At week 28, around 70% of the 27 secukinumab-treated patients were in sustained remission, defined as absence of flare while adhering to the steroid taper. This compared to a less impressive 20% of the 25 placebo-treated patients.
Forward to 52 weeks and 59% of patients in the secukinumab arm remained in sustained remission compared to only 8% of those given placebo.
We would hope that means that the secukinumab group used less prednisolone. At week 52, the placebo group has used an average of 3376 mg cumulatively. There was 16% less cumulative use in the secukinumab arm, an average 2841mg. That’s still a lot so hopefully we’ll see better results as we potentially become less passive with steroid taper. We do need more data however.
Then there’s safety. No unexpected signals were seen with little difference in overall safety between the groups.
We await the phase 3 study results.
- OP0182 Secukinumab in giant cell arteritis: the randomised, parallel-group, double-blind, placebo-controlled multicentre phase 2 TitAIN trial
