Table 2 Overview of studies evaluating the effect of inhibiting IL-1 on fatigue severity
From: Interleukin-1 as a mediator of fatigue in disease: a narrative review
Reference | Disease activity | Design | Number of patients | Fatigue questionnaire | IL-1 intervention | Main outcome |
|---|---|---|---|---|---|---|
Rheumatoid arthritis | ||||||
 Alten et al., 2011 | ≥6 of 28 tender and swollen joints, elevated hsCRP and/or ESR | Randomized, double-blind, placebo-controlled, parallel-group, dose-finding trial | 274 | FACIT-F at 12 weeks | MTX combined with canakinumab: (1.) 150mg s.c. every 4 weeks (n = 69), (2.) 300 mg s.c. every 2 weeks (n = 64), (3.) 600 mg i.v. followed by 300 mg s.c. every 2 weeks (n = 71) or placebo s.c. every 2 weeks (n = 70) | Decrease in fatigue canakinumab group 1 (p = 0.006) and 3 (p = 0.028) compared to placebo. |
 Omdal et al., 2005 | Mean DAS28 6.2 ± 1.1 | Pilot, non-blinded, no control group | 8 | FSS and VAS-fatigue at baseline, week 4, and week 8 | 100 mg s.c. anakinra daily | Decrease in FSS (p = 0.002) and VAS-fatigue (p = 0.0001) during the 8 weeks, accompanied by a decrease of the DAS28 score (p < 0.0001). |
Sjögrens syndrome | ||||||
 Norheim et al., 2012 | No elevation CRP/ESR | Randomized, double-blind, placebo-controlled, parallel-group trial | 26, 1 not included in analysis | FSS and VAS-fatigue at baseline, week 0, week 2, week 4, and week 5 | 100 mg s.c. anakinra (n = 12) or placebo (n = 13) daily during 4 weeks | No difference FSS scores after 4 weeks, more frequent reduction of VAS-fatigue of >50% in anakinra group (50 vs 8%, p = 0.03). |
CAPS | ||||||
 Kone-Paut et al., 2011 | Moderate or severe disease activity | Part 1. open-label, followed by part 2. which was a double-blind withdrawal phase in responders, ending with open-label part 3 | 35 | 5-point likert scale, daily first 15 days of part 1, weekly thereafter (physician and patient), FACIT-F | Single canakinumab (150 mg) dose in part 1 (n = 35), followed by canakinumab (n = 15) or placebo (n = 16) every 8 weeks for 24 weeks in part 2. At relapse or at end of part 2, patients were treated with canakinumab for 16 more weeks (n = 31). | Fatigue absent or minimal at the end of part 1 in >85% of patients paralleled by decreased disease activity. Increase FACIT-F at the end of part 1 (p < 0.05). Fatigue relapse in patients randomized to placebo in part 2. |
 Huemmerle- Deschner, 2011 | Disease activity requiring medical intervention | Open label, phase II trial | 7 (pediatric) | 5-point likert scale at post-treatment days 1 and 2, and weeks 1 and 5 (physician) | Canakinumab 150 mg or 2 mg/kg, repeated after 7 days in absence of complete response. | Fatigue was absent or minimal 1 day after canakinumab in all patients. This was accompanied by a decrease in disease activity. |
 Hoffman et al., 2008 | NLPRP3 mutation combined with classic FCAS/MWS symptoms | Part 1. 6-week randomized controlled trial, part 2A. open-label, 2B. randomized controlled trial | 47 | DHAF rating fatigue over previous 24 h | Part 1 loading dose of 320 mg rilonacept/placebo s.c. (n = 47), followed by weekly s.c. injections of 160 mg rilonacept/placebo. Part 2 (n = 46) weekly s.c. rilonacept 160 mg during 9 weeks followed by 9 weeks rilonacept/placebo. | Decrease in fatigue in part 1 (p < 0.001), relapse in those patients treated with placebo in part 2 (p < 0.001). |
Diabetes | ||||||
 Cavelti-Weder et al., 2011 | Type 2 diabetes | Randomized, double-blind, placebo-controlled trial | 30 | Fatigue scale for motor and cognitive functions | XOMA052/placebo (0.01–1 mg/kg) | At baseline, 53% of patients experienced mild-severe fatigue. One month after treatment, fatigue was increased in the placebo and lowest dosing group; in the two medium dosing groups, fatigue was slightly decreased; and in the two highest dosing groups, fatigue was remarkably decreased. Effect size dose-dependent effect d = 0.3. The highest dose of 1.0 mg/kg had a favorable effect on motor fatigue (d = 1.05). |
Cancer | ||||||
 Hong et al., 2015 [108] | Advanced non-small cell lung cancer | Open label dose escalation trial | 16 | EORTC-QLQ, at baseline and after 8 weeks | Intravenous MABp1 every 3 weeks trough 4 dosing levels (0.25/0.75/1.25/3.75 mg/kg, and 3.75 mg/kg every 2 weeks (until disease progression)) | Non significant improvement in fatigue severity. Median disease free progression was 57 days. |
 Hickish et al., 2016 | Metastatic colorectal cancer refractory to standard chemotherapy | Randomized controlled trial | 309 | EORTC-QLQ | MABp1 plus best supportive care or placebo (2:1) | Significant improvement of fatigue, increase in appetite, and decrease in pain severity |