Where Are We with RA?

WASHINGTON, D.C.—Despite a decade of progress in rheumatoid arthritis (RA), challenges remain. Remission is drug maintained. Multimorbidity abounds, and treatment strategies can be challenging for some. And, as of yet, RA is not preventable.

At ACR Convergence 2024, Iain McInnes, PhD, FRCP, director, Research into Inflammatory Arthritis Center, professor of medicine and rheumatology, vice principal and head of College and Veterinary and Life Sciences, University of Glasgow, Scotland, shared updates on RA.

Which Biologic?

We’re fortunate to have a multitude of treatment options for RA in 2024 and have come a long way from glucocorticoids and gold. But more drugs mean more choices, and it’s still not clear which drug will work best for which patient, or best … period.

“Guidelines exist [from the ACR and EULAR], but don’t tell us which drug to use,” Dr. McInnes noted. “Our choices are driven by cost, accessibility or ‘the drug I can spell most easily’ (i.e., the drug we’re most comfortable with).”

Dr. McInnes

The 2023 NORD-STAR trial attempted to answer the question of which biologic is best. “For a patient taking methotrexate who isn’t doing so well, which is the best of the biologics? According to these data, the answer is … any of them,” Dr. McInnes summarized. “Choose the drug you know best that will be best for the patient in regard to comorbidity and cost.” Of note, in this trial, clinical disease activity index for RA (CDAI) remission rates for patients taking abatacept (59.3%) or certolizumab pegol (52.3%) were superior to those taking tocilizumab (51.9%), but by a small margin.¹

Then Dr. McInnes turned toward the PERFECTRA trial, a pragmatic, multi-center, real-life study comparing treat-to-target strategies with baricitinib vs. tumor necrosis factor (TNF) inhibitors after failure of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Baricitinib was found to be non-inferior and superior to TNF inhibitors.²

“Janus kinase (JAK) inhibitors are very efficacious in people with RA, but you need to obey the black box warning,” he said. When prescribing a JAK inhibitor, the risk of adverse events and safety profile must be taken into account. They may be safe for some, but riskier for others.³

“Can I Stop My Meds, Doc?”

Over the past few years, we’ve seen tapering studies that allow us to better answer this question. The simple answer? Maybe. But it depends on the medication.

When it comes to methotrexate, we may be able to lower the dose with concomitant use of a TNF inhibitor. “In the MIRACLE trial, the dose of methotrexate could be reduced by nearly 50% at the time of initiation of the TNF inhibitor with no difference in response compared with those who continued maximal-dose methotrexate,” Dr. McInnes said.⁴

ARCTIC REWIND was a tapering study that looked at what happens when csDMARDs are tapered in patients in stable remission, which was defined as remission sustained for at least one year on stable doses of medications with no swollen joints at inclusion. Three-year data showed that halving the dose of csDMARDs and/or halving the dose and stopping the csDMARD after one year was associated with significantly lower rates of flare-free survival.⁵ However, it’s worth mentioning that it was possible to taper or stop csDMARDS in a subgroup of patients. Thus, shared decision making regarding flare risk in patients who want to try to taper off csDMARDs remains key.

As for biologics, ARCTIC REWIND TNFi looked at tapering TNF inhibitors in the same group of patients mentioned above, with continuation of csDMARDs.⁶ In the tapering TNF inhibitor group, 63% of patients experienced a flare within 12 months, compared with 5% of patients who continued their TNF inhibitor without changes.

The TOLEDO trial showed similar disappointing results when trying to reduce or space out the dosing of abatacept or tocilizumab.⁷ “It doesn’t appear to be wise to halve the dose or stop the biologic. If you’re on a [biologic] medicine you’ve got to kind of stay there,” Dr. McInnes remarked.

RA & Multimorbidity

For many of our patients, RA isn’t their only health issue. For example, obesity, cardiovascular disease and diabetes commonly affect our patients with RA, compounding the risk of comorbidity. And RA, in and of itself, increases the risk of developing cardiovascular disease.

Dr. McInnes shared that “evidence is growing for a critical interaction between RA and multimorbidity (two or more coincident conditions). In general, if you are multimorbid, you’ll have poorer outcomes and are more likely to die.”⁸

So what can we do about it? A lot. Options include, but aren’t limited to, controlling blood pressure, blood sugar, weight and cholesterol levels.⁹ “There are lots of actionable risks that you and I need to be actioning. I urge you to either do it yourself, or make sure the primary care doctor is doing it,” Dr. McInnes said.

Weight loss, in particular, is incredibly important because treating chronic diseases without tackling excess adiposity promotes multimorbidity.¹⁰ Dr. McInnes had some simple tips when it comes to having this conversation with our patients. He first urged us to “avoid stigma and start by asking if it’s okay to talk about weight.” Once consent has been obtained, assess the problem, agree on a plan and assist the patient in making small, positive changes. For example, Dr. McInnes advises his patients to “cut sugary drinks, add more fiber-rich foods proven to help weight loss, adapt the palate and add 500 steps per day initially—if pain/joints allow.”

Last, he reminded us to consider holistic approaches to pain, fatigue and mental health. “The management is way beyond pharmacology. There are guidelines from the ACR and EULAR to this effect. There is real biology at work here,” Dr. McInnes noted.^11,12

Preventing RA

As for the prevention of RA, Dr. McInnes briefly touched on three recent studies—APIPPRA, ARIAA and PRAIRI—that evaluated whether certain biologics could help prevent the development of full-blown RA in patients with pre-RA. APIPPRA and ARIAA showed that abatacept might show promise.^13,14 PRAIRI showed no benefit to single-dose rituximab at two years.¹⁵

In Sum

RA is complex, and the best care of the patient involves more than just controlling inflammatory arthritis and/or systemic manifestations of RA.

“Divide your patient into tissue states: immune state, brain state, bone state and cardiometabolic state,” Dr. McInnes counseled. When we think about the patient this way, we can truly provide whole-patient care.

Samantha C. Shapiro, MD, is a clinician educator who is passionate about the care and education of rheumatology patients. She writes for both medical and lay audiences and practices telerheumatology.

References

1. Østergaard M, van Vollenhoven RF, Rudin A, et al. Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial. Ann Rheum Dis. 2023 Oct;82(10):1286–1295.
2. van de Laar CJ, Oude Voshaar MAH, Ten Klooster P, et al. PERFECTRA: a pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs. RMD Open. 2024 May 30;10(2):e004291.
3. Szekanecz Z, Buch MH, Charles-Schoeman C, et al. Efficacy and safety of JAK inhibitors in rheumatoid arthritis: Update for the practising clinician. Nat Rev Rheumatol. 2024 Feb;20(2):101–115.
4. Tamai H, Ikeda K, Miyamoto T, et al. Reduced versus maximum tolerated methotrexate dose concomitant with adalimumab in patients with rheumatoid arthritis (MIRACLE): A randomised, open-label, non-inferiority trial. Lancet Rheumatol. 2023 Apr;5(4):e215–e224.
5. Kjørholt KE, Paulshus Sundlisæter N, Aga AB, et al. Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial. Lancet Rheumatol. 2024 May;6(5):e268–e278.
6. Lillegraven S, Paulshus Sundlisæter N, Aga AB, et al. Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: A randomised, open label, non-inferiority trial. Ann Rheum Dis. 2023 Nov;82(11):1394–1403.
7. Kedra J, Dieudé P, Giboin C, et al. Towards the lowest efficacious dose: Results from a multicenter noninferiority randomized open-label controlled trial assessing tocilizumab or abatacept injection spacing in rheumatoid arthritis in remission. Arthritis Rheumatol. 2024 Apr;76(4):541–552.
8. England BR. The multimorbidity web in rheumatoid arthritis. Rheumatology (Oxford). 2023 Oct 23;62(SI3):SI242–SI251.
9. Ferguson LD, Sattar N, McInnes IB. Managing cardiovascular risk in patients with rheumatic disease. Med Clin North Am. 2021 Mar;105(2):247–262.
10. Sattar N, McMurray JJV, McInnes IB, et al. Treating chronic diseases without tackling excess adiposity promotes multimorbidity. Lancet Diabetes Endocrinol. 2023 Jan;11(1):58–62.
11. Dures E, Farisoğulları B, Santos EJF, et al. 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases. Ann Rheum Dis. 2024 Sep 30;83(10):1260–1267.
12. England BR, Smith BJ, Baker NA, et al. 2022 American College of Rheumatology guideline for exercise, rehabilitation, diet, and additional integrative interventions for rheumatoid arthritis. Arthritis Care Res (Hoboken). 2023 Aug;75(8):1603–1615.
13. Rech J, Tascilar K, Hagen M, et al. Abatacept inhibits inflammation and onset of rheumatoid arthritis in individuals at high risk (ARIAA): A randomised, international, multicentre, double-blind, placebo-controlled trial. Lancet. 2024 Mar 2;403(10429):850–859.
14. Cope AP, Jasenecova M, Vasconcelos JC, et al. Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): A randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial. Lancet. 2024 Mar 2;403(10429):838–849.
15. Frazzei G, Cramer SHM, Landewé RBM, et al. The effect of rituximab on patient reported outcomes in the preclinical phase of rheumatoid arthritis: 2 year data from the PRAIRI study. RMD Open. 2024 Oct 18;10(4):e004622.