Study characteristics of the included trials

Ward et al. 2005 [24]The model considered the UK population (58.8 million)
Treatment outcome and resource use data were collected from an expert panel experienced in the treatment of post-stroke spasticity
IG: BTX-A injection (first-line)Cost/STM

Duration: 1 year
35% of patients receiving oral therapy showed an improvement in pre-treatment functional targets that would warrant continuation of therapy, compared with 73% and 68% of patients treated with BTX-A first- and second-line therapy, respectively
The cost/STM was £942 for BTX-A as first-line treatment, £1,387 for BTX-A as second-line treatment, and £1,697 for oral therapy alone
BTX-A is a cost-effective treatment for post-stroke spasticity
IG: anti-spastic drugs orals and BTX-A injection (second-line)
CG: anti-spastic oral drugs
Shaw et al. 2010 [25]n = 333 adults with upper limb spasticity at the shoulder, elbow, wrist, or hand and reduced upper limb function due to stroke more than 1 month previously
IG n = 170
CG n = 163
IG: BTX-A + 4-week programme of upper limb therapyMAS
Motricity Index
Grip strength
Nine-Hole Peg Test
Upper limb basic functional activity questions
Barthel Activities of Daily Living (ADL) Index
Stroke Impact Scale
Oxford Handicap Scale

Duration: 1, 3, and 12 months
No significant difference in IG vs. CG for improved arm function at 1, 3, and 12 months
Muscle tone/spasticity at the elbow was decreased in IG vs. CG at 1 month. No difference at 3 and 12 months
IG improved upper limb muscle strength vs. CG at 3 months. No difference at 1 and 12 months vs. CG
Significant difference IG vs. CG for improved specific basic functional activities at 1 and 3 months
Significant differences in the IG vs. CG for improvement of pain at 12 months
0.36 probability of BTX-A being cost-effective
BTX-A and a 4-week programme of upper limb therapy did not improve upper limb function at 1 month
However, improvements were seen in muscle tone, upper limb strength, upper limb functional activities related to undertaking specific basic functional tasks and upper limb pain. The addition of BTX-A to an upper limb therapy programme was not estimated to be cost-effective
CG: 4-week programme of upper limb therapy alone
Burbaud et al. 2011 [26]n = 870 adults with neurological disease with muscular spasms in relation to dystonia, spasticity, or nerve compression (hemifacial spasm)BTX-A injectionLatency of effect (in days)
Duration of effect (in weeks)
Daily cost of BTX-A (ratio of each session’s cost to the duration of subjective efficacy)

Duration: passed beyond the duration of efficacy (5 months)
The efficacy was significantly greater for facial hemispasm and blepharospasm vs. cervical dystonia, and for cervical dystonia vs. upper and lower limb spasticity
The daily cost of BTX-A injections was higher in cervical dystonia and upper and lower limb spasticity. When associated costs were considered, the daily cost of BTX-A injections was increased
These results show that BTX-A treatment has a low daily cost for a long-lasting effect, with a daily cost/benefit ratio that greatly depends on the indications
Doan et al. 2013 [27]n = 126
Epidemiology, efficacy, and health utilities data were taken from clinical trials done in Scotland on treating upper-limb post-stroke spasticity
IG: usual treatment in Scotland and onaBoNT-AEQ-5D

Duration: 1 year
IG improved disability, which translated into greater QALYs but also increased direct medical costs compared with CG. However, the resulting ICER can be considered cost-effective. Moreover, IG can be cost-saving if reduction in caregiver burden was includedIn the different scenarios studied, usual treatment in Scotland and BTX-A improved disability at a higher cost than usual treatment
CG: usual treatment in Scotland
Rychlik et al. 2016 [28]IG: n = 118 adults with upper limb post-stroke spasticityIG: antispastic therapy and incoBoNT-A
Two subgroups: IG pretreated and IG naive
Ashworth Scale (AS)

Duration: visit 1 (baseline visit) and continued visits every 12 weeks (visit 2, 3, 4) until the end of observation (visit 5)
Responder rates of all muscle groups of the upper limbs were significantly higher in the IG than CG
Significant differences in favour of the IG for the AS score, the four domains of the DAS, and both dimensions of SF-12—dimensions ‘Physical Health’ and ‘Mental Health’ from visit 1 to the end of the study
Total health service costs were twice high in IG, however, ICER was consistently superior compared to the CG
Higher responder rates, higher increases in QoL, and superior cost-utility ratios in the BTX-A treatment group underline guideline recommendations for BTX-A treatment in focal or segmental spasticity
CG: n = 110 adults with upper limb post-stroke spasticityCG: antispastic therapy (oral antispastic medications, physiotherapy)
Lazzaro et al. 2020 [29]IG: n = 864 adults with upper or lower limb post-stroke spasticityIG: rehabilitation + aboBoNT-ALYS

Duration: 2 years
IG costs double compared to CG
No difference in LYS
IG outperforms CG in terms of QALYs gained
ICUR was higher in IG
Rehabilitation + aboBoNT-A is a cost-effective healthcare programme for treating patients with post-stroke spasticity
CG: n = 66 adults with upper or lower limb post-stroke spasticityCG: rehabilitation only
Fernández Sanchis et al. 2022 [22]IG: n = 40 adults with upper limb hypertonia post-stroke (subacute)IG: normal rehabilitation
Programme with DN

Duration: baseline visit, 4 weeks, and 8 weeks
Statistically significant improvements were found for QoL in favour of the IG at 4 and 8 weeks
IG presented significant improvements according to the MMAS scale at 4 and 8 weeks
Based on the rate of responders, the ICER of the IG was very low. Despite the sensitivity analysis performed, the results of the ICUR did not show significant improvements
Cost-effectiveness with responder rate results was favourable for the DN group and was confirmed by the sensitivity analysis according to levels of care. In addition, the results revealed that 4 weeks of treatment could be more cost-effective than 8 weeks
CG: n = 40 adults with upper limb hypertonia post-stroke (subacute)CG: standard rehabilitation
Programme with neither DN nor a placebo
Turcu-Stiolica et al. 2020 [30]The model was based on a previous study carried out with 218 patients
Relevant clinical trials in adults with post-stroke upper limb spasticity
IG: incoBoNT-ASF-12

Duration: 3 and 5 years
IG proved to be more effective than CG in the treatment of upper limb post-stroke spasticity according to SF-12
Patients treated with IG had higher costs than CG
IG showed a more favourable ICER per QALY gained for both physical and mental health dimensions (ICER €950/QALY)
incoBoNT-A proved to be a more favourable treatment option than conventional therapy programme in the treatment of upper limb post-stroke spasticity, because it is highly cost-effective and improves QoL
CG: conventional therapy programme alone
Fernández-Sanchis et al. 2022 [23]IG: n = 11 adults with chronic post-stroke hypertoniaIG: single-session treatment of DNQoL

Duration: baseline visit and 2 weeks after treatment
Significant differences between groups in terms of QoL two weeks after the intervention in favour of IG
Favourable ICER of both €130.14/QALY and < €10/responder for IG
MMAS only showed statistically significant improvements in the elbow extensors for the IG
DN is an affordable alternative with good results in the cost-effectiveness analysis—both immediately, and after two weeks of treatment—compared to sham DN in persons with chronic stroke
CG: n = 12 adults with chronic post-stroke hypertoniaCG: single-session DN sham intervention

ADL: Activities of Daily Living; ARAT: Action Research Arm Test; CG: control group; EQ-5D: European QoL-5 Dimensions; ICER: incremental cost-effectiveness ratio; ICUR: incremental cost-utility ratio; IG: intervention group; LYS: life-years saved; MAS: Modified AS; MMAS: Modified MAS; QALY: quality-adjusted life year; DAS: Disability Assessment Scale; SF-12: QoL scale Short Form-12; SRS: Subjective 4-Point Rating Scale; STM: successfully treated months