Arthritis Disease Severity Peaks in Spring and Fall, According to PROs

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A seasonal correlation with patient-reported outcomes (PROs) were impacted by factors like sleep and fatigue among a group of patients with arthritis, with worse disease severity linked to spring and fall months, according to research presented at the 2024 European Congress of Rheumatology (EULAR).¹

“Inflammatory Arthritides (IA) cause complex flares, partly explained by factors like diet, lifestyle, and medications, prompting speculation about the influence of seasonality,” wrote a team of investigators led by Shreena Kamlesh Gandhi, MD, associated with the Kansas University School of Medicine.¹ “Studies suggest that winter and spring trigger most exacerbations, but findings are contentious due to symptom overlap with Seasonal Affective Disorder (SAD). It remains unclear whether seasons directly impact disease activity or through SAD-related symptoms.”

Similar research investigating the influence of seasonal changes on the clinical manifestation of rheumatoid arthritis (RA) has been previously reported. These results underscored an increase in disease activity among patients with RA during the spring, with results demonstrating the highest disease activity in the upper and lower extremities during these months. However, this study also identified fall as exhibiting the highest remission rates, with a significant difference in the Disease Activity Score-28 with C-reactive protein (DAS28-CRP) observed for fall compared with spring and winter, which does not align with the results extrapolated from the current study.²

To evaluate the seasonal variations in PROs in patients with inflammatory arthritis, investigators identified subjects using data from adults with RA, psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE) registered in the Forward Databank registry. Biannual questionnaires were completed using Patient Activity Score-II (PAS-II) measurements from 1998 to 2023. The primary outcome was PAS-II, averaging the patient global visual analog scale (VAS), pain VAS, and the Health Assessment Questionnaire-II (HAQ-II), and used the season as the exposure. If data from the HAQ-II were missing, investigators substituted the HAQ Disability Index (HAQ-DI) for PAS-II imputation.

Patients were evaluated at baseline and by season, and investigators averaged the available PROs. Various models adjusted for clinical variables, PROs including fatigue and sleep, comorbidities, demographics, and treatment.

In total, 47,052 subjects contributed to 406.215 observations during this period. The mean age of patients was 58 years, 19% were male, and most (84%) had RA. Higher PROs, which were indicative of worse disease activity, were more likely to be reported in the spring and fall months. The quasi-likelihood under the independence model criterion (QIC) scores decreased with the addition of more variables, demonstrating the increasing strength of the correlation structure

No differences in PAS-II were observed between winter and summer, although spring and fall reported the highest coefficients in Model 1 (season), with a difference in PAS-II of .13 (95% CI 0.11 – 0.14) and .10 (95% CI 0.09 – 0.12) higher, respectively, when compared with the summer months. Similar findings were observed through Model 5. However, Model 5 showed the same coefficient impact on PAS-II estimates for the winter, spring, and fall seasons, with only a .04 increase in PAS2 when compared with summer.

Investigators noted the most important factors for predicting seasonal variation of PAS-II scores were fatigue (Z-score 149), sleep (Z-score 74.86), education (Z-score -34.91), the duration of arthritis (Z-score 21.53), employment (Z-score -22.45), and treatment with prednisone (Z-sore 22.7).

“Future work will explore SAD and inflammation components, using varied outcomes and consider regional weather,” investigators concluded.

References

1. ^{Gandhi SK, Pedro S, Michaud K. Changing Seasons, Changing Joints: The Influence of Seasonal Variations on PROs in Patients with Inflammatory Arthritis. Presented at: EULAR. Vienna, Austria. June 12 – 15, 2024.}
2. ^{Mori H, Sawada T, Nishiyama S, et al. Influence of seasonal changes on disease activity and distribution of affected joints in rheumatoid arthritis. BMC Musculoskelet Disord. 2019;20(1):30. Published 2019 Jan 18. doi:10.1186/s12891-019-2418-2}