Work

RC9.5 - ECE_2071 - Replacing early morning cortisol reduces fatigue: post-hoc analysis of AddiQol in CHAMPAIN, a double-blind study comparing Chronocort and Plenadren

Year: 2026

Type: article

Abstract: Background Cortisol has a circadian rhythm with an early morning rise; loss of this rhythm is associated with poor health. In the CHAMPAIN study we demonstrated that twice daily Chronocort (Efmody, Immedica Netherlands B.V.), which replaces the early morning rise in cortisol, improved QoL compared to Plenadren (Takeda Ltd. UK), which only replaces daytime cortisol levels. This post-hoc analysis looked at the sub-domains of the disease specific questionnaire, AddiQoL (Addison's disease Quality of Life questionnaire) and SF-36 V2, compared to other questionnaires. Methods CHAMPAIN was a double-blind cross-over study in 58 patients with primary adrenal insufficiency (AI) comparing Chronocort, 15 mg at night and 10 mg in the morning, with once daily Plenadren 25 mg. The primary endpoint was waking cortisol and secondary endpoints were measures of fatigue and QoL. Patients signed informed consent and the trial was registered (NCT NCT05222152; Eudract 2021-000144-21). AddiQoL has four subdomains: fatigue, emotions, symptoms, and miscellaneous and was completed every 4 weeks within 2 hours of waking. A sensitivity analysis was done on period 1 of the cross-over which was randomised parallel-arm and blinded. P was one-sided, significance at P < .025. Results In the cross-over analysis treatment effect was in favour of Chronocort for AddiQoL: Total Score (+3.214, P = .024), and subdomain Fatigue (+1.234, P = .014), but not different for Emotions (+0.861, P = .032), Symptoms (+0.500, P = .157) and miscellaneous (+0.676, P = .033). In the sensitivity analysis Total Score was positive (+6.3, P = .0175). The SF-36 V2 physical component score which includes fatigue was in favour of Chronocort (+3.2, P = .01) but the Mental Component Score was not different (−0.6 P = .7). In the sensitivity analysis the following SF-36 subdomains significantly favoured Chronocort: Physical Functioning (+5.42 P = .004), Role Limitations due to Physical Health (+7.59 P = .001), Bodily Pain (+4.99 P = .022), General Health Perceptions (+5.70 P = .004), and Vitality (+7.16 P = .002). The PROMIS 7b, a specific fatigue questionnaire, was in favour of Chronocort (−2.6, P = .024). The most common adverse event was fatigue, reported by twice as many during Plenadren treatment (44.6%) compared to Chronocort (20.7%). Conclusions Replacing the early morning cortisol improved health related QoL in AI based on the disease specific questionnaire AddiQoL. This was primarily due to reduced fatigue which was also seen in the SF-36 physical component score and fatigue specific questionnaire PROMIS 7b and there were fewer reports of fatigue on Chronocort compared to Plenadren.

Source: European Journal of Endocrinology

DOI: 10.1093/ejendo/lvag096.196