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5 Articles in this Series
ACR Releases Updated Draft Guidelines for Juvenile Idiopathic Arthritis (JIA)
Debate: When Methotrexate Fails – The Use of JAK or TNF Inhibitors
Pharmacotherapy & Rheumatic Disease in Older Adults
Rheumatoid Disease Therapy and Immunological Complications
When Rheumatoid Arthritis Treatment Gets Difficult: 3 Cases Offer Potential Solutions

When Rheumatoid Arthritis Treatment Gets Difficult: 3 Cases Offer Potential Solutions

An ACR Convergence 2020 Meeting Highlight with John Richards, MBBS, Joan Bathon, MD, Stanley Cohen, MD, and Josef Smolen, MD

Rheumatoid arthritis now has many treatment options, allowing providers to tailor therapy to individual patients. However, when patients have chronic comorbidities on top of the disease, or when therapy after therapy fails, decisions about treatment and monitoring can be complex.

At ACR 2020 Convergence, three experts shared what they do in challenging cases, offering case examples from patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD), and with RA and liver disease (and hepatitis B), as well as what to do in cases of treatment-refractory RA.

Rheumatoid Arthritis and Interstitial Lung Disease

Within the RA population, the presence of ILD is about 10%, said Joan Bathon, MD, chief of rheumatology at Columbia University. The prognosis can be grim, she noted, with a median survival of 2.6 years and just 20% of those diagnosed surviving after 8 years.

She shared a case history of a 65-year-old man with RA, type 2 diabetes, and coronary artery disease. His ejection fraction (EF) test came back normal; additional tests and evaluation resulted in a diagnosis of ILD, RA, and new mild heart failure.

Among the treatment questions, she asked: Does methotrexate cause or worsen ILD?  “It seems unlikely,” she said, citing research evaluating more than 2,700 patients with a new diagnosis of RA given methotrexate. The same holds for leflunomide (Arava), she said.

Based on a review of additional studies, including the use of antifibrotics, Dr. Bathon observed that when a patient was off methotrexate and leflunomide, their RA symptoms worsened. Returning to the presented patient case, she noted that pulmonologists were concerned about a genetic etiology of the ILD due to a family history (this would translate to a higher infection risk). Ultimately, a decision was made to treat the patient’s RA with abatacept (Orencia) and the ILD with nintedanib (Ofev,  Vargatef). Evaluation of the patient is ongoing.


Managing Rheumatoid Arthritis in Patients with Liver Disease, Hepatitis B

“Liver damage is not an extra-articular manifestation of RA,” said Stanley Cohen, MD, clinical professor of internal medicine at UT Southwestern Medical School and medical director of the Metroplex Clinical Research Center, in his ACR talk. Among liver-related conditions to be aware of, he noted the following:

  • nonalcoholic fatty liver disease (NAFLD)
  • concomitant autoimmune liver diseases, such as primary biliary cholangitis(PBC), primary sclerosing cholangitis(PSC), autoimmune hepatitis
  • transaminitis secondary to NSAIDS, biologics, conventional synthetic and targeted synthetic DMARDs (csDmards, tsDmards)
  • infectious hepatitis
  • hepatitis B or C infection

He presented a case report of a 64-year-old female with symmetrical polyarthritis. Her exam revealed 14 tender joints, 6 swollen, with a CDAI of 30. X-rays showed no erosion; bilateral suprapatellar effusions.

She was placed on low-dose prednisone 5 mg a day with meloxicam with follow-up in 2 weeks to talk about DMARD prescription. A Quantiferon gold and hepatitis panel was ordered. The patient, at 2 weeks, was modestly improved, with 9 tender joints, 4 swollen. The Quantiferon gold was negative but the hepatitis B surface antigen was positive; the antibody negative, the core antibody positive, and the hepatitis C antibody negative. 

Sulfasalazine 2 gm/day was started; prednisone was continued and the patient was referred to a hepatologist, who reported she was a hepatitis B carrier. Although antiviral therapy was suggested, the patient refused. Disease activity fluctuated between low and moderate, but she sustained damage to her wrist and shoulder joint. Her hepatitis B viral DNA load remained low, at less than 1000 units/mL.

Doctors should also be aware of the scope of the HBV reactivation issue, Dr. Cohen said as he shared the case.  According to the WHO, in 2015, there were 257 million cases of chronic hepatitis B worldwide. It is a known complication of immunosuppressive therapy.

“All patients with a past history of HBV are at some finite risk of reactivation, regardless of the presence or absence of serologic markers,” he explained

He cited ACR recommendations for the use of DMARDs and biologics in the treatment of rheumatoid arthritis in the presence of a hepatitis B infection. For instance, in patients initiating any bDMARD or tsDMARD who are hepatitis B core antibody-positive and hepatitis B surface antigen-positive, prophylactic antiviral therapy is strongly recommended over frequent monitoring alone.


Refractory RA: How to Treat

Josef S. Smolen, MD, a rheumatologist at the Medical University of Vienna in Austria, opened his ACR 2020 talk with a clear definition of refractory rheumatoid arthritis: “The inability to reach the treat-to-target goals of remission or at least low disease activity despite various changes of therapy.”

To illustrate, he presented a case history of a 65-year-old woman with an 11-year history of RA. Results of ACPA and RF were both positive high titre. The patient had failed many therapies, including biologic DMARDS (methotrexate, two anti-TNF inhibitors, rituximab, abatacept).

She had 14 tender joints, 10 swollen. Her CDAI was 37.9. “Clearly this was refractory disease,” he told the audience.

The patient was prescribed a JAK inhibitor. At six week follow-up, she had 7 tender joints, 4 swollen, and her CDAI was 18. At 12-week follow-up, she had 3 tender joints, 2 swollen, with a CDAI of 8.5.

To prevent refractory RA, said Dr. Smolen, physicians must make a rapid diagnosis, initiate DMARD therapy promptly, and follow clinical treatment guidelines [he cited EULAR as an example] about switching therapies.

Treatment should aim for ”best care,” with shared decision-making with the patient, he noted, and should be adapted if the treatment aim is not reached within 3 to 6 months. Another key clinician consideration should be to look for a CDAI reduction of more than 50% by 3 months, target at 6 months.


Expert Perspective

The three topics covered – liver disease, ILD, and refractory RA – are just some of the challenges when caring for patients with rheumatoid arthritis and other comorbidities or treatment issues, John Richards, MBBS, section chief of rheumatology at the VA Pittsburgh Healthcare System, told Practical Pain Management. Renal disease and cancer also make treatment and treatment decisions challenging in this patient population, he said.

Among the take-home points of the panel, he said, is the importance of stratifying the level of risk for patients with hepatitis B, depending on the medications they are on, and deciding how often to monitor them.

As for individuals who may be refractory to RA treatment, he said that those who are not successfully treated after trying multiple DMARDs are in the minority, fortunately. However, remember, “when you do have a patient [who is refractory] it’s quite a challenge for the patient.”


Disclosures: Dr. Smolen reported consultancies and/or speaking engagements for Amgen, Astro, Lilly, Sanofi and others.




Kiely P, Busby AD, Nikiphorou E et. al. Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts.  BMJ Open. 2019;9:e028466.

Smolen JS, Landewe RBM, 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;79:685-699.


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