Curcumin as add-on therapy in patients with multiple sclerosis showing a suboptimal response to first-line disease-modifying therapies: clinical outcomes and in vitro data

In recent decades, pathogenetic therapy of multiple sclerosis (MS) has advanced significantly due to the development of disease-modifying therapies (DMTs), which are classified into first- and second-line drugs based on their efficacy and safety profiles. Curcumin is being considered as an add-on therapy due to its potential efficacy and favorable safety profile. Objective: to evaluate the effect of micellar curcumin on clinical and immunological parameters in MS patients receiving interferon (IFN) therapy, as well as to assess the in vitro effects of this polyphenol on cytokine production by macrophages (MFs) and peripheral blood mononuclear cells (PBMCs). Material and methods. As a result of randomization, MS patients (n=60) with a suboptimal response to IFNβtherapy were divided into two groups, one of which received additional therapy with micellar curcumin for 6 months (IFN-C group). Clinical (relapses, MRI activity, EDSS score, chronic fatigue according MFIS scale, quality of life according SF-36) and immunological (IL-6 and IFNγ levels) parameters were assessed before and after the study. The effect of curcumin on cytokine production by PBMCs and MFs in MS patients and healthy donors was also evaluated. Results. After 6 months, the IFN-C group showed a decrease in the proportion of patients with relapses (p=0.007), a reduction in the proportion of patients with new/enlarging lesions on T2 MRI (p=0.003), and stabilization of EDSS score (p=0.2), in contrast to the comparison group, which showed increased disability (p=0.03). Hazard ratio for exacerbation in the curcumin group compared to the control group was 0.2 (95% CI 0.09–0.89; p=0.03). This group also showed improvement in chronic fatigue (p=0.002) and quality of life (p=0.008 for physical and p=0.03 for mental components). No adverse events were reported during the observation period. After dietary enrichment, a lower level of IFNγwas detected in the plasma of patients receiving curcumin (p=0.02). In vitro results demonstrated a slight stimulatory effect of curcumin on IL-10 and an inhibitory effect on IL-6 and IFNγ. Conclusion. Based on the results of this pilot study, micellar forms of curcumin, that have an acceptable safety profile, may be considered as a potential adjunctive method to enhance the anti-inflammatory effect of IFNβin MS patients with suboptimal therapeutic response.