Patients diagnosed with rheumatoid arthritis (RA) and co-occurring anxiety or depression are less likely to achieve low disease activity (LDA) and better symptom control after 3 months of treatment, according to new research presented at the at the annual meeting of the Canadian Rheumatology Association.
The findings emphasized the importance of taking a multidisciplinary approach to RA treatment, said presenter Susan Bartlett, PhD, a professor in the Divisions of Clinical Epidemiology, Rheumatology, and Respiratory Epidemiology at McGill University in Montreal, Quebec, Canada.
McGill University
Dr. Susan Bartlett
“In the absence of directly addressing anxiety and depression, people are not going to improve to the same extent we hope that they will,” she told this news organization.
Symptom Clusters in RA
In her research, presented on February 29, Dr. Bartlett explored how certain symptom clusters in RA predicted prognosis.
Symptom clusters are related symptoms that occur together and can be associated with worse outcomes than one symptom alone. Symptom science has been a growing interest in precision medicine, particularly for cancer, Dr. Bartlett noted, and this same approach could help pinpoint RA subtypes, disease trajectories, and personalized treatment.
In the study, Dr. Bartlett and colleagues used data from the Canadian Early Arthritis Cohort (CATCH), a multisite prospective research study following individuals with new-onset RA. They identified patients starting methotrexate (MTX) therapy who also had clinical and patient-reported outcome measures available. Individuals included in the analysis may have also been taking additional disease-modifying antirheumatic drugs beyond MTX.
Across the 310 selected individuals, researchers identified four key symptoms: Pain, fatigue, anxiety, and depression. Pain and fatigue were defined as physical symptoms, while anxiety and depression were classified as emotional symptoms. Results showed that the patients could be sorted into four distinct symptom clusters: Minimal symptoms (12%), mild physical and emotional symptoms (11%), moderate to severe pain and fatigue (40%), and moderate to severe physical and emotional symptoms (37%).
Researchers then followed patients during the first 6 months of treatment to evaluate if patients’ symptoms improved.
Symptom improvement mostly occurred during the first 3 months of treatment and remained consistent at 6 months. Overall, patients with moderate to severe emotional symptoms had a worse prognosis and were less likely to achieve milder symptoms than those who had only pain and fatigue or mild emotional symptoms. While 64% of patients in the moderate to severe physical symptoms group achieved minimal symptoms after 3 months of treatment, only 13% of patients with moderate to severe physical and emotional systems reported minimal symptoms during this same time frame.
The study builds on previous work that “suggests that there are different factors that we can identify around the time of diagnosis that point to how well a person is likely to respond,” Dr. Bartlett added. “What our work is showing pretty clearly [is that] the presence of anxiety and depression is one of those important markers.”
Patients With Depression Report Worse Disease Activity
In a related study, researchers from the University of Ottawa explored how depression in RA affected subjective and objective disease measures.
The study included patients from the Ottawa Rheumatology Comprehensive Treatment and Assessment (ORCHESTRA) clinic at The Ottawa Hospital, Ottawa, Ontario, Canada, which sees patients with inflammatory arthritis who are starting biologic therapy or switching to another biologic. The clinic is designed to take a more comprehensive approach to managing inflammatory arthritis, including addressing comorbidities such as cardiac disease, depression, and cancer. Patients seen at the clinic can opt to be included in the ORCHESTRA cohort to be a part of ongoing research.
From this cohort, researchers identified 98 patients with RA. At enrollment, patients were screened for depression using patient health questionnaire scores and asked about duration of morning stiffness and tender joint counts. Swollen joint counts, ultrasound, and clinical scores were used to evaluate disease activity.
In the study group, 47 patients had no depression, 21 patients had mild depression, and 30 patients had moderate to severe depression. Researchers found that subjective disease measures, including visual analog pain scale, health assessment questionnaire, and disease activity score in 28 joints were all higher in patients with depression; however, depression did not appear to affect objective disease measures, such as the Global OMERACT-EULAR Synovitis Score or Doppler scores.
While there is a known link between inflammation and depression, these findings suggest that depression is “a concomitant comorbidity just like cardiovascular disease, just like fibromyalgia, just like some other comorbidity that also needs to be addressed in its own right to improve the outcomes,” noted Elliot Hepworth, MD, a rheumatologist and ORCHESTRA clinic lead at The Ottawa Hospital, in an interview.
Dr. Hepworth presented the findings on March 1.
Dr. Elliot Hepworth
Dr. Elliot Hepworth
The data also suggested that patients with depression had poorer outcomes. For the 79 patients who had 3-month follow-up visit data, 43.9% of patients with no or mild depression achieved LDA and remission compared with 21.7% of patients with moderate to severe depression, though this difference was not statistically significant (P = .064). There was a similar trend for the 39 patients with 6-month follow-up data: Only 20% of patients with moderate to severe depression had reached LDA and remission compared with 37.9% of patients with no or mild depression (P = .445). The researchers noted this could be an issue with a smaller sample size.
“Every time more patients get added we approach closer to significance,” Dr. Hepworth added.
Some Disagreement, Same Takeaway
Commenting on the Ottawa study, Dr. Bartlett was skeptical of the conclusion that depression may not directly influence disease activity. “There’s just too much good evidence these days that [depression] very much coexists with worse disease activity,” she said. “It is not in the person’s head.”
Dr. Hepworth added that patient-reported outcomes are important for clinicians to address during treatment.
“There’s the tender joints, there’s the pain, there’s the fatigue, there’s the patient global assessment, which are subjective,” he said, “but that does not mean that they are not important. Those are important to the patient: That is how they’re living their life, and that is how they’re experiencing their disease.”
This is why efforts to treat depression in patients with RA such as cognitive behavioral therapy are so important, he said, to which Dr. Bartlett agreed.
“A comprehensive approach is required, which includes addressing depression,” she said. Otherwise, data show “that people just never make it to remission.”
The studies looked at different patient populations but ultimately complement each other, added Sibel Aydin, MD, a professor of medicine in the Division of Rheumatology at the University of Ottawa, Ottawa, Ontario, Canada, and senior author of the Ottawa study.
Dr. Sibel Aydin
Dr. Sibel Aydin
“Two different cohorts with different patient populations still reached the same result,” she said. “If you don’t address the emotional aspect, you are not going to achieve the good outcomes.”
“It’s remarkable when you have two independent researchers coming to the same conclusion without ever talking to each other,” added Dr. Hepworth. “That really shows that this is something that’s pervasive, and it’s not just within our patient population.”
CATCH is funded by unrestricted research grants from programs with Pfizer, AbbVie, Roche, Sandoz, Fresenius Kabi, Organon, Viatris, JAMP, and Celltrion. Dr. Bartlett is president of the PROMIS Health Organization. She is a member of speakers bureaus or has consulted for Pfizer, Sandoz, Merck, Janssen, and Organon. Dr. Hepworth and Dr. Aydin declared no conflicts of interest.
A version of this article appeared on Medscape.com .