Clinical Edge Journal Scan Commentary: RA February 2022

Arundathi Jayatilleke, MD

Several recent RA studies have addressed aspects of systemic illness other than joint pain and inflammation, including sleep, fatigue, psychosocial burden, and well-being. A cohort study by Lyne et al ¹ evaluated sleep duration and quality in 3,265 patients in the Swedish EIRA registry from 1-12 years after RA diagnosis. About 40% had problems in at least one sleep domain and the frequency of sleep problems increased somewhat with disease duration, but the strongest correlations with poor sleep were pain and functional impairment, suggesting that the overall activity of the RA was most important. Further research on improving sleep quality with improved control of disease activity would be helpful in supporting this hypothesis.

A systematic review by Shamail et al ² examined mental health outcomes in patients with RA taking Janus kinase (JAK) inhibitors, limiting the review to studies reporting SF-36 mental health outcomes. The resulting 19 studies encompassed over 14,000 patients and did demonstrate clinically meaningful changes in SF-36 scores compared to baseline in patients treated with JAK inhibitors. When compared to changes with placebo or disease-modifying antirheumatic drug (DMARD) treatment, JAK inhibitors appeared to have a benefit, though few studies showed a clinically meaningful difference. Given that other studies have shown improvement in mental health outcomes with other classes of RA treatments, it is not clear that this is an effect of the JAK inhibitor class rather than related to overall improvement in quality of life.

Fatigue is a prevalent concern among patients with RA and may significantly impact quality of life; its origins in RA are not well-understood but thought to be related to inflammation. A UK study of an inception cohort by Ifeseman et al ³ examines fatigue in early RA; about 75% of participants reported a decreased vitality score compared to the mean in the UK general population. Of the approximately 729 study participants in the longitudinal analysis, trajectory modeling was used to identify two groups of people: one with an “average” vitality score and another with a score that was significantly reduced compared to average. This group had worse disease activity scores, Health Assessment Questionnaire (HAQ) scores, and pain, though as with the other studies mentioned above, it is not clear if fatigue is a feature of worse control of RA or related to ongoing central sensitization or “non-inflammatory” mechanisms.

Doumen et al ⁴ analyzed interaction between psychosocial variables and disease activity in an early RA cohort and found that better baseline short form-36 (SF-36) scores as well as other measures of psychosocial burden and coping were associated with sustained Disease Activity Score 28 for Rheumatoid Arthritis with C-Reactive Protein (DAS-28-CRP) remission, while negative illness perception was associated with lower probability of sustained remission. Of the 287 patients who achieved DAS-28-CRP remission at week 16, the 231 patients who had a low psychosocial burden were more likely to remain in remission. Causality and direction are not established in this small study, so while evaluating psychosocial needs is relevant, as with the other studies mentioned above, caution must be used in attributing lack of improvement in disease activity to psychosocial burden or mood disorders.

References

1. Lyne L et al. Sleep problems in rheumatoid arthritis over 12 years from diagnosis: results from the Swedish EIRA study. RMD Open. 2022;8:e001800 (Jan 5).
2. Shamail GMH et al. Association between janus kinase inhibitors therapy and mental health outcome in rheumatoid arthritis: A systematic review and meta-analysis. Rheumatol Ther. 2021 (Dec 13).
3. Ifesemen OS et al. Fatigue in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Network. Rheumatology (Oxford). 2021;keab861 (Dec 27).
4. Doumen M et al. Psychosocial burden predicts sustained remission in early rheumatoid arthritis: unraveling the complex interplay of wellbeing and disease activity. Arthritis Care Res (Hoboken). 2021 (Dec 20).