Experts Discuss Unique Challenges Posed by Difficult-to-Treat RA

Dr. Smolen.

ACR CONVERGENCE 2020—Patients with rheumatoid arthritis (RA) and concurrent liver disease or interstitial lung disease (ILD), or with treatment-refractory RA, pose treatment challenges, said panelists in the ACR Convergence 2020 session, How I Treat Difficult RA. Each panelist discussed a difficult case and raised big-picture questions on how to best treat patients facing each challenge.

RA & Interstitial Lung Disease

More data are needed to definitively choose the best treatment for RA and ILD, said Joan M. Bathon, MD, professor of medicine and chief of the Division of Rheumatology, Columbia University College of Physicians and Surgeons, New York City. In her talk, Dr. Bathon presented the case of a 65-year-old man found to have RA-ILD, as well as probable heart failure. She used the case as a springboard for treatment questions for combined RA-ILD.

Dr. Bathon reviewed treatment questions that arise with combined RA-ILD, which occurs in about 8% to 15% of RA patients. The condition has significant mortality, with a median survival of 2.5 years. In one study she shared, about 25% of those with RA-ILD died in the first year after diagnosis.¹

One question is whether methotrexate and leflunomide increase the risk for ILD. Study findings with methotrexate have mixed results, and not many studies focused on this for leflunomide. Overall though, these common RA therapies don’t appear to increase the risk for ILD, Dr. Bathon said.

As to whether a disease-modifying anti-rheumatic drug (DMARD) that can be used both for arthritis and ILD exists, the answer is maybe, Dr. Bathon said. She said that, so far, results for tumor necrosis factor inhibitors have been controversial and open-label studies with abatacept suggested a lack of worsening after starting the treatment for RA-ILD. A trial called FaSScinate, which investigated tocilizumab for systemic sclerosis, found less worsening of disease in the tocilizumab-treated group.^2,3 Still, this is another question for which more data and studies are needed, she added.

When discussing whether such antifibrotics as nintedanib or pirfenidone would be more efficacious than a DMARD for RA-ILD, Dr. Bathon pointed out that no direct comparison data exist. For the fibrotic subtype of ILD, she says nintedanib or perfinodone may be most appropriate to use as they target inhibiting growth factors. In clinical practice, Dr. Bathon said she relys on the preferences of the pulmonologist helping to treat her patients with RA-ILD.

Best Ways to Manage Refractory RA

With many efficacious drugs available, rheumatologists should switch to other agents when the ones currently used clearly do not work in difficult-to-treat RA patients, said Josef Smolen, MD, emeritus professor of medicine at the Medical University of Vienna.

Some reasons RA may be difficult to manage include lack of patient adherence, such comorbidities as heart disease and ILD, and refractory RA. A few key studies have focused on the definition of refractory RA, Dr. Smolen said, with one recent study from the European League Against Rheumatism defining it as moderate to high disease activity after one conventional and two biologic DMARDs have failed.^4,5

Dr. Smolen shared a flow chart he and his co-authors recently published that suggests a possible timeline for treating refractory RA. This includes changing the biologic DMARD or Janus kinase inhibitor to see if the patient improves by three months or reaches their treatment target by six months.⁶ Trying a new treatment within a certain time period instead of relying on a treatment that doesn’t work can help eliminate the unnecessary use of medications, he said.

Liver Disease & RA

Concurrent liver disease with RA presents its own set of challenges, said Stanley Cohen, MD, clinical professor in the Department of Internal Medicine at UT Southwestern Medical Center and co-medical director of the Metroplex Clinical Research Center, Dallas.

Liver disease is not an extra-articular manifestation of RA, but certain liver diseases commonly appear in RA patients. Those include nonalcoholic fatty liver disease, concomitant autoimmune liver diseases, infectious hepatitis, and hepatitis B and C. Although hepatitis C is now less common due to the availability of new treatments, hepatitis B is still a factor rheumatologists must consider before starting therapy, Dr. Cohen said.

Dr. Cohen shared facts about hepatitis B reactivation while discussing the case of a 64-year-old woman with symmetric polyarthritis who was found to have hepatitis B reactivation. The World Health Organization estimates 257 million people around the globe suffer from chronic hepatitis B. Patients can be asymptomatic, or they could have liver failure or even die from the viral reactivation. However, screening and management can help prevent reactivation, Dr. Cohen said.

With many efficacious drugs available, rheumatologists should switch to other agents when the ones currently used clearly do not work in difficult-to-treat RA patients.

Rheumatologists should screen patients for hepatitis B or C before starting new DMARD therapy, Dr. Cohen said, noting many practitioners don’t do this. In addition, rheumatologists should follow the ACR’s 2016 guideline regarding hepatitis B and DMARDs and biologics to treat RA.⁷ One recommendation from the guideline is that in patients starting rituximab therapy who are hepatitis B core antibody positive, prophylactic antiviral therapy is strongly recommended, as opposed to just monitoring liver enzymes and viral load. This is also recommended regardless of hepatitis B surface antigen status.

Vanessa Caceres is a medical writer in Bradenton, Fla.

References

1. Bongartz T, Nannini C, Medina-Velasquez YF, et al. Incidence and mortality of interstitial lung disease in rheumatoid arthritis: A population-based study. Arthritis Rheum. 2010 Jun;62 (6):1583–1591.
2. Fernandez-Diaz C, Loricera J, Castañeda S, et al. Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter of 63 patients. Semin Arthritis Rheum. 2018 Aug;48(1):22–27.
3. Khanna D, Denton CP, Jahreis A, et al. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): A phase 2, randomized, controlled trial. Lancet. 2016 Jun 25;387:2630–2640.
4. Roodenrijs NMT, de Hair MJH, vander Goes MC, et al. Characteristics of difficult-to-treat rheumatoid arthritis: Results of an international survey. Ann Rheum Dis. 2018 Dec;77(12):1705–1709.
5. Nagy G, Roodenrija NM, Welsing PM, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2020 Oct 1;annrheumdis-2020-217344. [Epub ahead of print.]
6. Smolen JS, Landewé RMB, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020 Jun;79(6):685–699.
7. Singh JA, Saag KG, Bridges Jr SL, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016 Jan;68(1):1–26.