Table Info

Table 1.

Study characteristics of the included trials

Study	Participants	Intervention	Outcomes	Results	Conclusion
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 therapy	MAS Motricity Index Grip strength ARAT Nine-Hole Peg Test Upper limb basic functional activity questions Barthel Activities of Daily Living (ADL) Index Stroke Impact Scale EQ-5D Oxford Handicap Scale QALYs 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
Shaw et al. 2010 [25]		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 injection	Latency of effect (in days) SRS 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-A	EQ-5D QALYs ICER 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 included	In the different scenarios studied, usual treatment in Scotland and BTX-A improved disability at a higher cost than usual treatment
Doan et al. 2013 [27]		CG: usual treatment in Scotland	EQ-5D QALYs ICER Duration: 1 year
Rychlik et al. 2016 [28]	IG: n = 118 adults with upper limb post-stroke spasticity	IG: antispastic therapy and incoBoNT-A Two subgroups: IG pretreated and IG naive	Ashworth Scale (AS) DAS SF-12 ICER 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
Rychlik et al. 2016 [28]	CG: n = 110 adults with upper limb post-stroke spasticity	CG: antispastic therapy (oral antispastic medications, physiotherapy)
Lazzaro et al. 2020 [29]	IG: n = 864 adults with upper or lower limb post-stroke spasticity	IG: rehabilitation + aboBoNT-A	LYS QALYs ICUR 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
Lazzaro et al. 2020 [29]	CG: n = 66 adults with upper or lower limb post-stroke spasticity	CG: rehabilitation only	LYS QALYs ICUR Duration: 2 years
Fernández Sanchis et al. 2022 [22]	IG: n = 40 adults with upper limb hypertonia post-stroke (subacute)	IG: normal rehabilitation Programme with DN	MMAS EQ-5D QALYs ICER ICUR 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
Fernández Sanchis et al. 2022 [22]	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-A	SF-12 QALY ICER 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
Turcu-Stiolica et al. 2020 [30]		CG: conventional therapy programme alone	SF-12 QALY ICER Duration: 3 and 5 years
Fernández-Sanchis et al. 2022 [23]	IG: n = 11 adults with chronic post-stroke hypertonia	IG: single-session treatment of DN	QoL QALYs MMAS ICER 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
Fernández-Sanchis et al. 2022 [23]	CG: n = 12 adults with chronic post-stroke hypertonia	CG: 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

Declarations

Author contributions

DF and PH contributed conception and design of the study; DF and EMGT organized the database and extracted data; DF, EMGT, SC, CR, and CP wrote the first draft of the manuscript; DF, EMGT, PH, and MFL elaborated the final draft. All authors contributed to manuscript revision, read and approved the submitted version.

Conflicts of interest

Pablo Herrero owns the DNHS^® trademark.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Data can be requested from the first author by email to efernandez@usj.es.

Funding

Not applicable.

Copyright

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