Summary of findings 2. Oral gabapentin compared to placebo for adults with SMA types II and III.

Oral gabapentin compared to placebo for adults with SMA types II and III
Patient or population: adults with SMA types II and III Setting: outpatient clinic Intervention: oral gabapentin Comparison: placebo
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo	Risk with oral gabapentin
Change in disability score assessed with: SMAFRS Scale: 0–50 Follow‐up: 12 months	The median change in the SMAFRS score was 0 in the gabapentin group (37 participants) and –2 in the placebo group (34 participants)		—	66 (1 RCT)	⊕⊕⊝⊝ Lowa,b	Higher scores on the SMAFRS indicate better function.
Change in muscle strength assessed as: % change in total muscle strength from baseline Follow‐up: 12 months	The mean change in muscle strength was –2.2%	MD 3.3% higher (6.9 lower to 14 higher)	—	50 (1 RCT)	⊕⊕⊝⊝ Lowb,c	—
Acquiring ability to walk Follow‐up: 12 months	0/35 participants in the placebo group developed the ability to walk at 9 or 12 months' follow‐up	0/38 participants treated with oral gabapentin developed the ability to walk at 9 or 12 months' follow‐up	—	73 (1 RCT)	⊕⊕⊝⊝ Lowa,b	—
Change in quality of life assessed with: change (%) from baseline in mini‐SIP Scale: 0–19 Follow‐up: 12 months	The mean change in quality of life was –0.26%	MD 0.36% higher (0.29 lower to 1 higher)	—	67 (1 RCT)	⊕⊕⊝⊝ Lowa,b	Higher scores on the mini‐SIP indicate poorer health status.
Change in pulmonary function assessed with: FVC (in % predicted) Follow‐up: 12 months	The mean change in pulmonary function was –2.9 % predicted	MD 1.1 % predicted lower (4.1 lower to 1.9 higher)	—	65 (1 RCT)	⊕⊕⊝⊝ Lowb,c	Data from analysis of participants who completed ≥ 2 visits.
Time from beginning of treatment to death or full‐time ventilation Follow‐up: 12 months	0 reported deaths and 0 participants required full‐time ventilation		—	84 (1 RCT)	⊕⊕⊕⊝ Moderatea	—
Adverse events related to treatment Follow‐up: median 12 months	Adverse events were reported to be infrequent and not statistically different between treatment groups. Numerical data on adverse events were not available.		—	65 (1 RCT)	⊕⊕⊝⊝ Lowd,e	Adverse events were systematically, prospectively collected at every study visit.
*The risk in the intervention group (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). CI: confidence interval; FVC: forced vital capacity; MD: mean difference; mini‐SIP: mini‐Sickness Impact Profile; PedsQL: Pediatric Quality of Life Inventory; RCT: randomised controlled trial; RR: risk ratio; SMA: spinal muscular atrophy; SMAFRS: Spinal Muscular Atrophy Functional Rating 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.

^a Downgraded one level for imprecision because the small sample size.
 ^b Downgraded one level for risk of bias. Incomplete data at 12‐month follow‐up and it was unclear why cases dropped out. Three cases (two treated, one placebo) were excluded from analysis because of extreme outcomes (greater than three standard deviations).
 ^c Downgraded one level because of imprecision; small sample size, inadequate for optimal information size (OIS).
 ^d Downgraded one level because no data on adverse events were available.
 ^e Downgraded one level for imprecision because the small sample size is unlikely to have captured uncommon adverse events.