## 3 Results
### Treatment Responders (TR) and Treatment Non-Respenders (TNR)  
Twelve weeks after nabiximols start, 46 (48%) patients improved by at least 30% at sNRS score and were classified as treatment responders (TR), while the remaining 49 (52%) were classified as treatment non-responders (TNR). Median number of daily nabiximols doses was similar in TR and TNR (6 [IQR 3-8] vs. 5 [IQR 0-8], \(p=0.292\)). TR showed a significantly lower median sNRS (3 [2-4] vs. 6 [5-8], \(p<0.001\)), pNRS (2 [2-4] vs. 5 [3-7], \(p<0.001\)), gNRS (4 [2-8] vs. 7 [5-9], \(p=0.01\)), and uNRS (3 [1-5] vs. 4 [2-6], \(p=0.05\)) when compared to TNR.  
Univariate linear regression analysis investigating possible predictors of nabiximols response showed an association between treatment responder status and EDSS score (OR = 0.73, 95% CI: 0.57-0.92; \(p=0.01\)). Instead, the concomitant use of other pharmacological treatments for spasticity, age, gender, disease duration, concomitant use of physiotherapy, and use of disease-modifying therapies were not associated with responder status. No associations were found in the multivariable model (Table 2).  
In a further analysis focusing on spasticity-related pain, we found an improvement of at least 30% in pNRS score at 12 weeks of treatment to be associated with EDSS score (OR = 0.62, 95% CI: 0.48-0.81; \(p<0.001\)), disease duration (OR = 0.95, 95% CI: 0.912-0.990; \(p=0.015\)), and concomitant use of other pharmacological treatments for spasticity  
\begin{table}
\begin{tabular}{l c c c c} \hline \hline
**Independent Variables** & **B** & **OR** & **95\% C.I. for OR** & \(p\) \\ \hline
**Univariate analysis** & & & & \\ \hline Age (per year of age) & \(-0.031\) & 0.969 & 0.937–1.003 & 0.072 \\ \hline Sex (female vs. male) & 0.390 & 1.477 & 0.614–3.553 & 0.384 \\ \hline Disease duration & \(-0.025\) & 0.975 & 0.938–1.014 & 0.204 \\ \hline EDSS & \(-0.319\) & 0.727 & 0.571–0.925 & 0.010 \\ \hline Physiotherapy & \(-0.067\) & 0.935 & 0.179–4.884 & 0.936 \\ \hline Disease modifying treatments & 0.409 & 1.505 & 0.623–3.639 & 0.364 \\ \hline Other spasmolytic drugs & \(-0.756\) & 0.469 & 0.198–1.111 & 0.085 \\ \hline
**Multivariable analysis** & & & & \\ \hline Age (per year of age) & \(-0.018\) & 0.983 & 0.942–1.025 & 0.413 \\ \hline Sex (female vs. male) & 0.274 & 1.315 & 0.486–3554 & 0.590 \\ \hline Disease duration & 0.001 & 1.001 & 0.954–1.050 & 0.982 \\ \hline EDSS & \(-0.247\) & 0.781 & 0.578–1.056 & 0.109 \\ \hline Physiotherapy & 0.723 & 2.060 & 0.301–14.106 & 0.462 \\ \hline Disease modifying treatments & \(-0.041\) & 0.960 & 0.338–2.726 & 0.939 \\ \hline Other spasmolytic drugs & 0.705 & 2.024 & 0.767–5.342 & 0.154 \\ \hline \hline \end{tabular}  
* B: Coefficient; C.I.: Confidence interval; OR: odds ratio; \(p\): Significant \(\leq 0.05\).  
\end{table}
Table 2: Regression models investigating associations between clinical characteristics and improvement by at least 30% in sNRS after 12 weeks of treatment.  
(OR = 0.38, 95% CI: 0.16-0.94; \(p\) = 0.035) at the univariate model. However, EDSS score only maintained association at the multivariable model (OR = 0.68, 95% CI: 0.51-0.91; \(p\) = 0.008) (Supplementary Table S1).