Patients Interrupting DMARD Use Well Into the COVID-19 Pandemic

Jeff Craven

February 17, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

The COVID-19 pandemic led to a decrease in the proportion of patients with rheumatic diseases who stopped taking their disease-modifying antirheumatic drugs (DMARDs), but the percentage who interrupted DMARD treatment increased later in the pandemic, according to speakers at the 2022 Rheumatology Winter Clinical Symposium.

"People seem to be less anxious, but they're interrupting their DMARD therapy more, more recently than in the pits of COVID, if you will," said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, and director of RWCS.

Dr John J. Cush (left) and Dr Arthur Kavanaugh

Kavanaugh and his copresenter Jack Cush, MD, were discussing the results of a recent study published in Arthritis Care & Research that evaluated 2,424 patients with rheumatic diseases who completed a baseline and at least one follow-up survey issued by patient organizations between March 2020 and May 2021, with a median of five follow-up surveys completed. The patients included in the study were aged a mean of 57 years, 86.6% were women, 90.5% were White, 41.8% had rheumatoid arthritis (RA), 14.8% had antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and 12.4% had psoriatic arthritis. Overall, 52.6% were on biologics or a Janus kinase (JAK) inhibitor, 30.0% were receiving methotrexate, 21.4% were taking hydroxychloroquine, and 28.6% were receiving low-dose (24.0%) or high-dose (4.6%) glucocorticoids.

Patients' T-scores on the anxiety short form Patient-Reported Outcomes Measurement Information System (PROMIS) survey significantly decreased from a score of 58.7 in April 2020 to a score of 53.7 in May 2021 (P < .001), but there was a significant decrease in the interruption of DMARD treatment between April and December 2020 (11.2% vs. 7.5%; P < .001). This percentage rose significantly to 14.0% by May 2021 (P < .001). Patients who stopped using DMARDs were significantly associated with predicted incidence of severe flare in the next survey in adjusted models (12.9% vs. 8.0%; odds ratio, 1.71; 95% confidence interval, 1.23-2.36).

The results tell us "that we as a discipline are not doing a good job educating our patients," said Cush, a rheumatologist based in Dallas, Tex., and executive editor of

"I wish we – and I'm really talking about myself – but myself and my practice were more proactive when COVID happened [in] sending out regular bulletins: 'Don't stop your therapy; these are the things you get; get the test that you need to get done,' " he said. "We let a lot of things go on autopilot with the patient driving throughout COVID. Even now, it's happening. And this is a problem, and there are going to be consequences to this."

Kavanaugh agreed with Cush's assessment, suggesting that the pandemic came up quickly enough that it was difficult to be proactive with the situation.

Patients on JAK Inhibitors as New COVID-19 Risk Group?

Another standout study on COVID-19 from 2021 was an analysis of the COVID-19 Global Rheumatology Alliance physician registry that examined risk of COVID-19 severity for patients with RA taking biologic or targeted synthetic DMARDs (tsDMARDs), which was presented at the 2021 EULAR congress and later published in Annals of the Rheumatic Diseases.

The researchers evaluated 2,869 patients March 2020 and April 2021 who were receiving abatacept (237 patients), rituximab (364 patients), interleukin (IL)-6 inhibitors (317 patients), JAK inhibitors (563 patients), or tumor necrosis factor (TNF) inhibitors such as infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab (1,388 patients) before developing COVID-19. Data about biologics or tsDMARDs were collected as a drug class. Patients in the study were mostly White (69.0%) women (80.8%) with a mean age of 56.7 years who lived in Europe (51.8%) or North America (35.0%). The researchers examined the severity of COVID-19 among all patients studied and calculated odds ratios based on drug class, with the TNF inhibitor group serving as a reference.

"[I]n this case, they said that the baseline use of rituximab was associated with more severity, and you see the severity being hospitalization and ICU and deaths. They found a signal for the JAK inhibitors that is not found in the other studies," Kavanaugh said.

Overall, they found 21% of patients in the registry were hospitalized and 5.5% died, with rituximab (OR, 4.15; 95% CI, 3.16-5.44) and JAK inhibitors (OR, 2.06; 95% CI, 1.60-2.65) associated with more severe COVID-19 outcomes. Specifically, rituximab was associated with greater likelihood of hospitalization (OR, 4.53; 95% CI, 3.32-6.18), hospitalization with oxygen/ventilation (OR, 2.87; 95% CI, 2.03-4.06), need for mechanical ventilation (OR, 4.05; 95% CI, 3.08-5.33), and mortality (OR, 4.57; 95% CI, 3.32-9.01), compared with TNF inhibitors. For JAK inhibitors, there was also a greater likelihood of hospitalization (OR, 2.40; 95% CI, 1.78-3.24), hospitalization with oxygen/ventilation (OR, 1.55; 95% CI, 1.04-2.18), need for mechanical ventilation (OR, 2.03; 95% CI, 1.56-2.62), and mortality (OR, 2.04; 95% CI, 1.58-2.65), compared with the TNF inhibitors group. Associations between COVID-19 severity and abatacept or IL-6 inhibitors were not identified.

Commenting on the study in a question-and-answer session, Roy Fleischmann, MD, said the part of the study that identified a signal for JAK inhibitors was "very interesting." He called attention to a rapid response comment to the study, which questioned if it was the drug class itself that caused the risk for severe disease. "This is very important, because actually, the patients who stop the JAK [inhibitor], that's what drove the illness. The patients [who] continued the JAK [inhibitor], very few of them had illness," said Fleischmann, clinical professor of medicine at the University of Texas Southwestern Medical School and codirector of the Metroplex Clinical Research Center, both in Dallas, Tex.

Confusion Among Patients During COVID-19

Alvin Wells, MD, PhD, asked the copresenters during the Q&A session whether they had any clinical pearls for the audience on how they manage treatment of patients with rheumatic disease with potential COVID-19 risk. "I think the confusion with our patients and COVID is what the ACR has put out with their guidelines," said Wells, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc.

Cush said he has three rules he follows: lower and discontinue steroids, avoid rituximab as a starting treatment and negotiate if patients are already taking it, and don't stop any therapy.

"I want disease control. I think being under control is what keeps you away from risk of COVID and hospitalization," Cush said. "I think being uncontrolled and inflamed, whether it's our [patients with] inflammatory arthritis or lupus or, worse, vasculitis [or] myositis, those are the ones at high risk of progression from being just infected to being sick and in the hospital."

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, posed the question of getting somewhat back to normal during COVID-19 with regard to recently infected patients presenting at infusion centers, whether patients are more likely to continue testing positive, and when patients are cleared to come back. Ruderman said his center has a 20-day rule for returning after having COVID-19, while Cush said his center allows patients to come in if they test negative after 7-10 days.

"One of the things we're struggling with is our infusion center, and one of the questions that keeps coming up is when can people come back after a COVID infection?" he said. "If you're on a drug at home, that's up to you and the patient. But in the infusion [center], then you have other people sitting around there."

Kavanaugh said there is no current data for how long patients with rheumatic disease shed virus, or how long a positive test can be measured. "You definitely will continue to shed, and you'll be detectable for a while," he said.

Cush and Kavanaugh reported having financial relationships with numerous pharmaceutical companies.

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