Table 5.
Summary of Findings for Nabiximols to Treat Spasticity (Clinical Question 5)
| Outcomes | Description | No. of participants IG/CG (studies) | Certainty of the evidence (GRADE) |
|---|---|---|---|
| Symptom burden (meta-analysis) (Collin et al., 2010,23 Novotna et al., 2011,24 Notcutt et al., 201225) | The meta-analysis showed a significant difference between groups for spasticity NRS (mean difference −0.51, 95% CI −0.96 to −0.07) | 614 309/305 (3 RCTs) |
⊕⊕⊕⊖ MODERATEa |
| Symptom burden (MAS) (Collin et al., 2010,23 Novotna et al., 2011,24 Notcutt et al., 201225) | There were no significant differences between groups in the MAS scores | 614 309/305 (3 RCTs) | ⊕⊕⊕⊖ MODERATEa |
| Symptom burden (SGIC) (Novotna et al., 2011,24 Notcutt et al., 201225) | There were significant differences between groups favouring nabiximols | 277 142/135 (2 RCTs) | ⊕⊕⊕⊖ MODERATEa |
| ADL (Collin et al., 2010,23 Novotna et al., 201124) | There was a significant difference between groups in Novotna et al. favouring nabiximols, but not in Collin et al. | 578 291/287 (2 RCTs) |
⊕⊕⊖⊖ LOWa,b |
| QOL (Collin et al., 2010,23 Novotna et al., 201124) | There was no difference between groups in Collin et al. (EQ-5D, MSQOL-54) and Novotna et al. (EQ-5D, SF-36) | 578 291/287 (2 RCTs) | ⊕⊕⊕⊖ MODERATEa |
| CGIC (ease of transfer, meta-analysis) (Collin et al., 2010,23 Novotna et al., 2011,24 Notcutt et al., 201225) | The meta-analysis of CGIC showed a significant difference between groups (OR 1.99, 95% CI 1.17–3.38) | 614 309/305 (3 RCTs) | ⊕⊕⊕⊖ MODERATEa |
| Adverse events (Collin et al., 2010,23 Novotna et al., 2011,24 Notcutt et al., 201225) | Collin et al.: A total of 55 patients (16%) discontinued treatment early; 35 (21%) in the nabiximols group and 20 (12%) in the placebo group. Of these 55 patients, 32 (58%) withdrew from the study. The primary reason given for withdrawal was AE occurrence: nine patients (5%) on nabiximols and five (3%) on placebo. The following AEs were reported more frequently in the nabiximols group compared to placebo: dizziness [53/167 (32%) vs. 17/170 (10%)], fatigue [42/167 (25%) vs. 32/170 (19%)], somnolence [24/167 (14%) vs. 7/170 (4%)], nausea [53/ 167 (32%) vs. 17/170 (10%)], asthenia [26/167 (16%) vs. 11/170 (6%)] and vertigo [19/167 (11%) vs. 7/170 (4%)]. Two subjects died from cancer during the study: neither death was considered to be related to the (active) study medication Notcutt et al.: There was one SAE (pain in hip and thigh and lumbar spinal stenosis) in a patient on nabiximols, which was considered unrelated to study medication. The only AE reported in association with abnormal laboratory values was a mild increase in gamma-glutamyl transferase in one patient on nabiximols. Novotna et al.: 17 patients discontinued the treatment early (7%); 15 were on nabiximols (four due to AEs, 11 due to withdrawal of consent). AEs were overall few and similar between nabiximols and placebo, with no single event occurring at a rate >10% in either group; the most common AEs were vertigo (6% nabiximols vs. 1% placebo) and fatigue (5% vs. 1%) |
614 309/305 (3 RCTs) |
⊕⊕⊕⊖ MODERATEa |
Patient or population: people with severe multiple sclerosis (and spasticity). Setting: research hospitals, outpatients. Intervention: nabiximols (2.7 mg D9-tetrahydrocannabinol and 2.5 mg cannabidiol, up to 24 sprays in 24 h) for 4–15 weeks. Comparison: placebo. GRADE Working Group grades of evidence. High certainty: there is great confidence that the true effect lies close to that of the estimate of the effect. Moderate certainty: there is moderate confidence 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: there is very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of the effect. ADL, activities of daily living; AE, adverse event; CG, control group; CGIC, carer global impression of change; CI, confidence interval; EQ-5D, EuroQol-5 Dimensions; IG, intervention group; MAS, modified Ashworth scale; MSQOL-54, Multiple Sclerosis Quality of Life 54 items; NRS, numerical rating scale; OR, odds ratio; QOL, quality of life; RCT, randomized controlled trial; SAE, serious adverse event; SF-36, 36-item Short Form Health Survey; SGIC, subjective global impression of change. aSevere risk of bias. bInconsistency.