OP0276-HPR DAY-TO-DAY FLUCTUATIONS OF FATIGUE IN SYSTEMIC SCLEROSIS

Abstract

BackgroundSystemic sclerosis (SSc) is a rare auto-immune disease with a huge impact on physical health as well as social well-being, with fatigue being the major problem experienced by patients with respect to their well-being [1]. While fatigue is being reported to be fluctuating and unpredictable, the dynamic nature of fatigue is not well understood [1, 2].ObjectivesTo examine the within-person fluctuations and clinically meaningful changes in fatigue, as well as the within-person association of fatigue and time-varying determinants in SSc.MethodsWe performed a daily-diary study in adult patients with a clinical diagnosis of SSc. Patients with pulmonary hypertension or severe pulmonary function disturbances (i.e. vital capacity and diffusing capacity for carbon monoxide < 50%) were excluded. During 14 days patients completed daily assessments at four fixed time points (i.e. 9 a.m., 1 p.m., 5 p.m., 9 p.m.) of fatigue severity and time-varying determinants (i.e. negative affect, positive affect, pain, quality of sleep and perceived exertion of physical activity. As proxy for clinical meaningful change in fatigue the probability of acute change(PAC) was assessed, i.e. the chance that change in day-to-day fatigue levels exceeded the minimally clinical important difference for fatigue[3]. Using multilevel models the within-person fluctuations in fatigue and its association with time-varying determinants were examined. Based on the extent of clustering, the time-varying determinants were disentangled into their corresponding levels (within persons (within day as well as across days) and between persons) and added to the multilevel model. Models were adjusted for confounding (i.e. BMI, sex, age, and history of covid-infection) where appropriate.ResultsFifty-seven patients with SSc, 35% male with mean(SD) age 54.3(14.6) years, participated. The disease duration was mean(SD) 6.9(4.8) years and 29.8 % was diagnosed with diffuse cutaneous SSc. Eighty percent of all observations were completed. During the study period, change in day-to-day level fatigue exceeded the MCID mean(SD) 5.7(1.9) times. The PAC was mean(SD) 0.44(0.14), ranging from 0.08-0.77. For fatigue a between-person variation of 49% and a within-person variation of 51% was observed. With respect to confounders, only BMI was significant in the models for time-varying negative and positive affect. The final models showed significant within-person association with fatigue fluctuations and changes in time-varying determinants within a day, between days and between patients (Table 1).ConclusionThis is the first quantitative study showing that fatigue in SSc is characterized by a dynamic course and that approximately half of the day-to-day fluctuations are clinically meaningful, confirming the results of qualitative studies[2]. Moreover, when patients reported more fatigue than usual, they also reported more pain, more negative affect, less positive affect, more perceived exertion of physical activity, and worse quality of sleep than usual.Table 1.Association of within-person fluctuations of fatigue and time-varying determinants at each level. All β are significant (p-value< 0.05). * corrected for BMI, β: regression coefficient, N/A: not applicable.Within-person fatigue fluctuationβ (95% ci) level 1within- dayβ level(95% ci) 2between daysβ level (95% ci) 3between patientsNegative affect *0.44(0.37, 0.51)0.41(0.31, 0.50)0.72(0.46, 0.98)Positive affect *-0.60(-0.66, -0.53)-0.61(-0.69, -0.53)-0.74(-1.05, -0.42)Pain0.46(0.39, 0.52)0.49(0.37, 0.62)0.48(0.33, 0.62)Perceived exertion of physical activity0.19(0.15, 0.24)0.25(0.16, 0.35)0.76(0.48, 1.04)Quality of sleepN/A-0.20(-0.27, -0.14)-0.48(-0.80, -0.16)References[1]Basta F et al., Clin Exp Rheumatol. 2018;36 Suppl 113(4):150-60.[2]Nakayama A et al., J Rheumatol. 2016;43(7):1363-75.[3]Khanna D et al., J Rheumatol. 2008;35(12):2339-43.Disclosure of InterestsArthiha Velauthapillai: None declared, Madelon Vonk Speakers bureau: Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen, MSD, Novartis and Roche, Consultant of: Boehringer Ingelheim and Janssen, Grant/research support from: Research grants from Boehringer Ingelheim, Janssen,Ferrer and Galapagos, Cornelia van den Ende: None declared, Johanna E. Vriezekolk Speakers bureau: Eli Lilly, but not pertaining to this study.