Background/Purpose: Quality of life in rheumatoid arthritis (RA) patients can be improved by reducing the common symptom of fatigue caused by disease related factors such as pain and inflammation.  Recent studies indicate that glucocorticoid treatment improves patient reported fatigue (Westoff et al, 2011). Chronotherapy with a modified (delayed) release (MR) prednisone tablet may also improve these symptoms. NP01 (Horizon Pharma, Deerfield IL) is a proprietary MR formulation of prednisone that results in a 4 hour delay in traditional pharmacokinetic parameters of prednisone. This formulation capitalizes on known cytokine and endogenous biologic rhythms. Here we report fatigue scores from the Circadian Administration of Prednisone in Rheumatoid Arthritis-2 (CAPRA-2) study which evaluated patients with active RA on stable disease-modifying antirheumatic drugs (DMARDs) given MR prednisone or placebo.

Methods: The study was a 12-week, double-blind, placebo-controlled study that randomized 350 RA patients to either 5 mg MR prednisone (n=231) or placebo (n=119) taken once daily at bedtime (eg, 10pm) in addition to their standard DMARD treatment (Buttgereit et al, 2012). The primary endpoint was the proportion of patients achieving ACR20 response after 12 weeks. A secondary objective was to compare treatment with 5 mg MR prednisone and placebo in the change from baseline on the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) questionnaire. This 13 item questionnaire assesses the effect of fatigue on daily activity and function on a 5‑point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much), with a score range of 0 to 52.

Results: The mean baseline FACIT-F fatigue score was comparable in the 5 mg MR prednisone group and the placebo group (28.81 vs 28.73, Table 1). The least square mean (LSM) absolute increase from baseline to Week 12 was greater in the 5 mg MR prednisone group than in the placebo group (3.83 vs 1.59), indicating a reduction of fatigue (Table 1). The difference in FACIT-F score between baseline and Week 12 was clinically relevant for 5 mg MR prednisone but not for placebo (minimal clinically important difference [MCID]: 3-4; Cella et al, 2005). At Week 12, the LSM change from baseline was statistically significantly greater for 5 mg MR prednisone than for placebo, (LSM difference=2.24 [95% CI: 0.76, 3.72], p-value=0.0032) (Table 1). Similar results occurred for observed case data. These findings were consistent with improvement in ACR20 score.

Table 1: FACIT-F Fatigue Score at Each Visit (mITT Population, BOCF)

Visit		FACIT-F Fatigue Score
		5 mg MR-Prednisone	Placebo	5 mg MR-Prednisone vs. Placebo
Baseline	n	231	119	–
	Mean (SD)	28.81 (10.443)	28.73 (10.725)	–
Week 12	n	231	119	–
	Mean (SD)	32.54 (10.893)	30.25 (10.465)	–
Absolute Change from Baseline to Week 12	LSM	3.83	1.59	–
	LSM Difference (SE)	–	–	2.24 (0.754)
	95% CI for LSM Difference	–	–	0.76, 3.72
	p-value	–	–	0.0032
Abbreviations: FACIT-F = Functional Assessment of Chronic Illness Therapy – Fatigue; mITT = modified intention-to-treat; BOCF = baseline observation carried forward; MR = modified-release; SD = standard deviation; LSM = least square mean; SE = standard error; CI = confidence interval.
Note: LSMs are from an analysis of covariance (ANCOVA) model with baseline results, treatment, and geographic region as factors. Model effects were from the Type III estimates.

Conclusion: Patients treated with 5 mg MR prednisone had significant improvement in FACIT‑F scores compared with placebo, indicating a reduction in fatigue and improvement in an important aspect of quality of life. Chronotherapy with a MR prednisone formulation improves ACR scores and provides a potential new treatment option for patients with RA that can also improve symptoms of fatigue.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/improved-fatigue-related-quality-of-life-in-capra-2-a-12-week-study-of-5-mg-modified-delayed-release-prednisone-in-rheumatoid-arthritis/