Summary of findings 2. Serlopitant 1 mg compared to placebo for chronic pruritus of unknown origin.

Serlopitant 1 mg compared to placebo for chronic pruritus of unknown origin
Patient or population: chronic pruritus of unknown origin Setting: 25 US centres Intervention: serlopitant 1 mg Comparison: placebo
Outcomes	Number of participants (studies), Follow‐up	Certainty of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects* (95% CI)
				Risk with placeboe	Risk difference with serlopitant 1 mg
Patient‐reported pruritus intensity Assessed with: participants with a ≥ 4‐cm reduction in average visual analogue scale (VAS range 0 to 10 cm). A reduction in VAS score indicates improvement Follow‐up: 6 weeks	126 (1 RCT)	⊕⊕⊝⊝ Lowa	RR 1.50 (0.89 to 2.54)	Study population
				254 per 1000	127 more per 1000 (28 fewer to 391 more)
Adverse events Assessed with: number of participants with any adverse event Follow‐up: 6 weeks	128 (1 RCT)	⊕⊝⊝⊝ Very lowb	RR 1.45 (0.86 to 2.47)	Study population
				254 per 1000	114 more per 1000 (36 fewer to 373 more)
Health‐related quality of life Assessed with: Dermatology Life Quality Index (DLQI) score (range 0 to 30). A higher score indicates greater impairment Follow‐up: 6 weeks	128 (1 RCT)	⊕⊝⊝⊝ Very lowc	‐	Mean health‐related quality of life was 20.6	MD 6.90 lower (14.38 lower to 0.58 higher)
Sleep disturbances: number of participants with insomnia Assessed with: Pittsburgh Sleep Symptom Questionnaire (the questionnaire reports insomnia as a dichotomous outcome) Follow‐up: 6 weeks	128 (1 RCT)	⊕⊝⊝⊝ Very lowd	RR 0.38 (0.17 to 0.84)	Study population
				286 per 1000	177 fewer per 1000 (237 fewer to 46 fewer)
Depression Assessed with: not measured	‐	‐	‐	‐
Patient satisfaction Assessed with: not measured	‐	‐	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DLQI: Dermatology Life Quality Index; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio; VAS: visual analogue scale.
GRADE Working Group grades of evidence. High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

^aDowngraded by two levels to low‐certainty evidence: one level due to indirectness, as 45% of patients had an underlying diagnosis (not meeting the pruritus of unknown origin criterion); and one level due to imprecision because of small sample size.

^bDowngraded by three levels to very low‐certainty evidence: one level due to some concerns regarding selection of the reported result; one level due to indirectness, as 45% of patients had an underlying diagnosis (not meeting the pruritus of unknown origin criterion); and one level due to imprecision, as few events and wide confidence interval.

^cDowngraded by three levels to very low‐certainty evidence: one level due to some concerns regarding selection of the reported result; one level due to indirectness, as 45% of patients had an underlying diagnosis (not meeting the pruritus of unknown origin criterion); and one level due to imprecision, as the confidence interval crosses the minimal important difference threshold for the DLQI questionnaire (between 3 and 5).

^dDowngraded by three levels to very low‐certainty evidence: one level due to some concerns regarding risk of bias in selection of the reported result and risk of bias due to missing outcome data; one level due to indirectness, as 45% of patients had an underlying diagnosis (not meeting the pruritus of unknown origin criterion); and one level due to imprecision, as few events and wide confidence interval.

^eRisk in the comparison group is based on the number of events (dichotomous data) or the mean (continuous data) in the control group of the one included study.