Cytokine Inhibition in Patients With Chronic Fatigue Syndrome: A Randomized Trial
Megan E. Roerink, MD(1); Sebastian J.H. Bredie, MD(1), PhD; Michael Heijnen; Charles A. Dinarello, MD(2); Hans Knoop, PhD(3); Jos W.M. Van der Meer, MD, PhD(1)
1) Department of Internal Medicine, Radboud University Medical Centre, Geert Groteplein Zuid 8, PO Box 9101, 6500 HB Nijmegen, the Netherlands.
2) University of Colorado Medical Center, 12700 East 19th Avenue, B168, Aurora, CO 80045.
3) Department of Medical Psychology, Academic Medical Centre (AMC), University of Amsterdam, Postbox 22660 J3 209, 1100 DD Amsterdam, the Netherlands.
Interleukin-1 (IL-1), an important proinflammatory cytokine, is suspected to play a role in chronic fatigue syndrome (CFS).
To evaluate the effect of subcutaneous anakinra versus placebo on fatigue severity in female patients with CFS.
Randomized, placebo-controlled trial from July 2014 to May 2016. Patients, providers, and researchers were blinded to treatment assignment. (ClinicalTrials.gov: NCT02108210)
University hospital in the Netherlands.
50 women aged 18 to 59 years with CFS and severe fatigue leading to functional impairment.
Participants were randomly assigned to daily subcutaneous anakinra, 100 mg (n = 25), or placebo (n = 25) for 4 weeks and were followed for an additional 20 weeks after treatment (n = 50).
The primary outcome was fatigue severity, measured by the Checklist Individual Strength subscale (CIS-fatigue) at 4 weeks. Secondary outcomes were level of impairment, physical and social functioning, psychological distress, and pain severity at 4 and 24 weeks.
At 4 weeks, 8% (2 of 25) of anakinra recipients and 20% (5 of 25) of placebo recipients reached a fatigue level within the range reported by healthy persons. There were no clinically important or statistically significant differences between groups in CIS-fatigue score at 4 weeks (mean difference, 1.5 points [95% CI, −4.1 to 7.2 points]) or the end of follow-up. No statistically significant between-group differences were seen for any secondary outcome at 4 weeks or the end of follow-up. One patient in the anakinra group discontinued treatment because of an adverse event. Patients in the anakinra group had more injection site reactions (68% [17 of 25] vs. 4% [1 of 25]).
Small sample size and wide variability in symptom duration; inclusion was not limited to patients with postinfectious symptoms.
Peripheral IL-1 inhibition using anakinra for 4 weeks does not result in a clinically significant reduction in fatigue severity in women with CFS and severe fatigue.
PRIMARY FOUNDING SOURCE
Interleukin Foundation and an independent donor who wishes to remain anonymous.
From Fatigue: Biomedicine, Health & Behavior, 2 March 2017
Two year follow-up of sleep diaries and polysomnography in chronic fatigue syndrome: A cohort study
Sean L. Davidson (1), Zoe M. Gotts (2,3), Jason G. Ellis(4) & Julia L. Newton (1,5)
1. Clinical Academic Office, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne, UK
2. Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK
3. Newcastle University Institute for Ageing, Newcastle University, Newcastle ups Tyne’s, UK
4. The Northumbria Centre for Sleep Research, Northumbria University, Newcastle upon Tyne, UK.
5. Newcastle upon Tyne Hospitals NHS Foundation Trust.
Chronic fatigue syndrome (CFS) is a prevalent and debilitating symptom complex of unknown aetiology. Up to 96.8% of people with CFS report unrefreshing sleep and many describe, in qualitative interviews, changes in sleep over the course of their illness.
To establish whether subjective and objective sleep parameters change over a two-year follow-up period in patients with CFS.
Twenty-two participants with CFS were recruited during routine consultations at a clinic in the North-East of England. All had their sleep characterised in a previously published cross-sectional study. Two were excluded from this analysis because they fulfilled criteria for a primary sleep disorder. The remaining 20 were contacted and 15 repeated fatigue- and sleep-quality questionnaires and sleep diaries, two years after their sleep was first characterised. Seven participants also repeated two consecutive nights of polysomnography. Paired statistical tests were used to compare follow-up with baseline measures.
Subjective questionnaires and sleep dairies did not show differences over two years follow-up. However, polysomnography demonstrated a higher proportion of stage one sleep (P < .01) and more awakenings per hour (P = .04) at follow-up. CONCLUSIONS This study is the first to longitudinally assess sleep parameters in people with CFS. The results suggest that subjective perceptions of sleep remain stable, although objective measures indicated a tendency towards increased periods of lighter sleep. However, the small number of participants increases the likelihood that observed differences are Type I errors.