Research abstract:
Background:
Interleukin-1 (IL-1), an important proinflammatory cytokine, is suspected to play a role in chronic fatigue syndrome (CFS).
Objective:
To evaluate the effect of subcutaneous anakinra versus placebo on fatigue severity in female patients with CFS.
Design:
Randomized, placebo-controlled trial from July 2014 to May 2016. Patients, providers, and researchers were blinded to treatment assignment. (ClinicalTrials.gov: NCT02108210)
Setting:
University hospital in the Netherlands.
Patients:
50 women aged 18 to 59 years with CFS and severe fatigue leading to functional impairment.
Intervention:
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).
Measurements:
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.
Results:
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]).
Limitation:
Small sample size and wide variability in symptom duration; inclusion was not limited to patients with postinfectious symptoms.
Conclusion:
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 Funding Source:
Interleukin Foundation and an independent donor who wishes to remain anonymous.
Cytokine Inhibition in Patients With Chronic Fatigue Syndrome: A Randomized Trial by Megan E. Roerink MD; Sebastian J.H. Bredie, MD, PhD; Michael Heijnen; Charles A. Dinarello, MD; Hans Knoop, PhD; Jos W.M. Van der Meer, MD, PhD in Annals of Internal Medicine [Published online: 7 March 2017]
Comments:
ME association blog post, 8 March 2017, Dr Charles Shepherd: Why we shouldn’t dismiss the role of pro-inflammatory cytokines in ME/CFS: comment on Annals of Internal Medicine paper
Phoenix rising ME/CFS Forum posts, 7 March+: Comments by Prof Jonathan Edwards and others
