Can we stop RA before it happens? Save
Rheumatologists have long hoped and wondered whether the right type of early intervention could prevent rheumatoid arthritis occurring in at-risk individuals. While it is often a point of substantive discussion at EULAR, this year’s meeting in Copenhagen provided further data on how therapy might useful before patients develop rheumatoid arthritis (RA), particularly for those at particularly high risk.
Much has been made previously of the progression from risk to systemic autoimmunity, and subsequently the development of inflammatory arthritis eventually declaring itself as RA, with the hallmark being the presence of clinical synovitis. Before this stage, however, many patients experience substantive symptoms of RA, and even changes on MRI suggestive of RA, without developing clinical synovitis. While such patients with clinically suspect arthralgias seem obvious candidates for treatment to arrest the progression to RA, multiple previous studies have failed to show that treating such patients prevents any of them from developing RA.
Following initial data at ACR Convergence 2021, Dr. Jurgen Rech presented further data from the ARIAA study, a RCT examining the value of six months of abatacept in such patients with ACPA positivity and MRI findings (Rech et al. POS0531). While a benefit was evident at the end of the abatacept therapy period, more impressive were the results twelve months after abatacept was stopped – with 65% of patients on abatacept not developing synovitis, compared to 43% of patients receiving placebo. While abatacept is plausibly particularly useful in interrupting citrullination, even in this select group the cost and number needed to treat will potentially raise questions about the feasibility of such an approach.
Methotrexate is a more affordable and familiar therapy, and Dr. Doortje Krijbolder and colleagues from Leiden in the Netherlands presented a proof-of-concept double-blinded RCT, looking at patients with MRI-detected subclinical joint inflammation and treated for one year with methotrexate, before being followed for a further year (Krijbolder et al. OP0070). While this did not show any difference in RA development at the end of the total 24 month study period, it did lead to substantial improvements in physical function, pain, morning stiffness, and presenteeism. It raises a question as to whether, despite conventional wisdom, there might be value in using methotrexate to treat patients without clinical synovitis.
In a survey I ran during the meeting, I asked Twitter what they would recommend methotrexate to a patient with 12 weeks of inflammatory-sounding arthralgias, functional impairment, high-titer rheumatoid factor and ACPA, osteitis on MRI, but no clinical synovitis on exam. An overwhelming majority (72%) of the 178 participants voted yes, with only 3% ruling out therapy. In an anonymous poll which is prone to unveil candid honesty, rheumatologists seemed to suggest that the absence of clinical synovitis does not prevent them from prescribing DMARDs.
Finally, it should be noted that when all else fails in healthcare, the market solution is vitamins – usually without any evidence. In contrast, at the meeting Dr. Karen Costenbader presented further analyses from the VITAL study, which examined the role of vitamin D and fish oil supplementation in vitamin D replete healthy people (Costenbader et al. OP0038). Further analyses presented at this meeting showed a trend towards benefit of vitamin D 2000 IU daily in preventing the development of incident rheumatoid arthritis, although no effect from omega-3 supplementation. While even before the VITAL study the merits of vitamin D supplementation in healthy people remained a point of substantive contention in the broader medical community, these data will just fuel further questions about how most rheumatoid arthritis develops in the first place.
Costenbader et al. BMJ 2022 https://www.bmj.com/content/376/bmj-2021-066452