Summary of findings 5. Canakinumab versus placebo for reducing inflammation in familial Mediterranean fever.
| Canakinumab versus placebo for familial Mediterranean fever | ||||||
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Patient or population: people with colchicine‐resistant familial Mediterranean fever Settings: outpatient (more than 20 centers from Italy, Spain, Israel, the Netherlands, the USA, France, the UK, Turkey, Belgium, Russia, Switzerland, Japan and Hungary) Intervention: canakinumab Comparison: placebo | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Placebo | Canakinumab | |||||
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Number of participants experiencing an attacka Follow‐up: 16 weeks |
938 per 1000 | 384 per 1000 (244 to 609) | RR 0.41 (0.26 to 0.65) | 63 (1 study) | ⊕⊕⊕⊝ Moderateb | RR < 1 indicates an advantage to canakinumab. Number of participants experiencing an attack were analyzed; there was a difference at 16 weeks favoring canakinumab (RR 0.41, 95% CI 0.26 to 0.65). |
| Duration of attacks | Not reported. | |||||
| Time between attacks | Not reported. | |||||
| Prevention of AA amyloidosis | Not reported. | |||||
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Adverse drug reactions Follow‐up: 16 weeks |
De Benedetti 2018 reported the rate of serious adverse events per 100 patient‐years among people with colchicine‐resistant familial Mediterranean fever. This was 42.7 with canakinumab and 97.4 with placebo. | 63 (1 study) | ⊕⊕⊕⊝ Moderateb | The most frequently reported adverse events were infections, abdominal pain, headaches and injection site reactions (De Benedetti 2018). | ||
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Acute‐phase response Follow‐up: 16 weeks |
De Benedetti 2018 reported the proportion of participants with a CRP level ≤ 10 mg/L was 68% with canakinumab vs 6% with placebo (P < 0.001). | 63 (1 study) | ⊕⊕⊕⊝ Moderateb |
De Benedetti 2018 did not report CRP and SAA concentration. P < 0.05 indicates an advantage to canakinumab. |
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| De Benedetti 2018 reported the proportion of participants with an SAA level ≤ 10 mg/L was 26% with canakinumab vs 0% with placebo (P = 0.0572). | ||||||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). AA: amyloid A; CI: confidence interval; CRP: C‐reactive protein;PGA: Physician's Global Assessment of disease activity; RR: risk ratio; SAA: serum amyloid A protein. | ||||||
| GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: we are very uncertain about the estimate. | ||||||
aAttack definition: none resolution of the baseline flare at day 15 (PGA score < 2 plus CRP level ≤ 10 mg/L or a reduction by ≥ 70% from baseline) or new flare (PGA score of ≥ 2 and CRP level ≥ 30 mg/L) (or both) until week 16. bDowngraded one level for the small sample size.