1. Head-to-head monotherapy of anti-IL-6 sarilumumab vs. adalimumab shows that sarilumumab 200 mg SC q2w is superior. (Abstract #3221, Burmester G, et al)
This is similar to tocilizumab monotherapy vs adalimumab monotherapy so it may indeed be a class effect of IL-6>TNFi in monotherapy
2. Drug levels of baricitinib (particularly 4 mg daily) predicted time to ACR and DAS28 responses – using data from multiple trials (Ernest CSE, Abstract #1584)
Overall JAKs have a very fast onset – just like 'Jak Jak' the speedy boy from The Incredibles
Dose matters for speed of onset
3. If we switch from a TNFi to an oral JAK inhibitor, we don't need to wash patients out. Switching from ADA to baricitinib without a washout yielded improvements in disease activity after the head-to-head superiority trial of baricitinib vs. adalimumab (added to MTX) and there were no new safety signals (Taylor PC. Abstract #1591, BEAM; and RCT: Taylor PC et al. Arthritis Rheumatol 2015;67(S10):3927-3928).
4. In early RA, if you withdraw the biologic (TNFi) the patient may indeed flare, but the patient may flare even while on a biologic – the holy grail of sustained remission is tough to achieve.
In an RCT of certolizumab pegol (Weinblatt M, et al. Abstract #952), active ERA patients were treated with MTX alone or MTX with certolizumab for 1 year and if patients were in sustained low disease state, they were randomized to stay on, reduce the dose of, or withdraw certolizumab in year 2, whereas the group on MTX from year 1 who were doing well stayed on MTX for year 2.
2/3 were eligible to enter year 2 and and half the patients on standard and low-dose certolizumab maintained sustained low disease activity for year 2 compared to 39% who stopped the TNFi.
5. Will treating aggressively early in RA reduce the need for biologics? Some cohorts of ERA have shown this, but the Canadian early RA cohort did not.
Front end loading of DMARDs in an ERA cohort does not prevent time to biologic prescription, but use of subcutaneous MTX reduced need for and time to biologic use. Gottheil S, et al ( Abstract #3149)* presented data showing that combination DMARDs in early RA did not delay onset of TNFi by time and proportion of users. There may be confounding due to access to TNFi routinely requiring combination DMARDs in Canada.
*J Pope is an investigator for this study
Dr. Janet Pope is Professor of Medicine at Western University and Division Head of Rheumatology. Dr. Pope's research interests include epidemiologic studies in scleroderma, classification criteria in systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis.
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