Abstract
Background
multiple sclerosis (MS) is a complex disease sustained by several pathogenic mechanisms.
As such, combination therapy strategies, targeting a range of disease mechanisms,
might represent the ideal therapeutic approach. Here we investigated the efficacy
of curcumin, a naturally occurring poly-phenolic phytochemical with potent anti-inflammatory
and antioxidant properties, in subjects under treatment with IFN β-1a, to test the
effects of this combination therapy on clinical and MRI parameters of inflammation
and neurodegeneration in relapsing MS (RMS).
Methods
eighty active RMS were prospectively enrolled, randomized (1:1) to either the IFN-curcumin
or the IFN-placebo group and followed up longitudinally with clinical and MRI assessments
for 24 months. Primary endpoint was the efficacy of curcumin versus placebo as add-on
therapy on new/enlarging T2 lesions in RMS subjects under treatment with subcutaneous
IFN β-1a 44 mcg TIW. Efficacy on clinical parameters (relapses and disability progression),
other MRI parameters of inflammation (T1 Gd-enhancing lesions, combined unique active-CUA
lesions) and neurodegeneration (T1-hypointense lesions, grey matter loss and white
matter microstructural damage) as well as safety and tolerability of curcumin were
explored as secondary endpoints.
Results
ten subjects dropped out from the study by month 12 (6 in the IFN-curcumin group and
4 in the IFN-placebo group), and 27 by month 24 (11 in the IFN-curcumin group and
16 in the IFN-placebo group). Although no between-group difference was present in
terms of proportion of subjects free from new/enlarging T2 lesions, a lower proportion
of patients with CUA lesions was noted at month 12 in the IFN-curcumin group in comparison
with the IFN-placebo group (7.5% vs 17.5%, χ² test p= 0.0167). This result was not confirmed at month 24. The statistical analysis failed
to reveal any difference between the two treatment groups – IFN-curcumin and IFN-placebo
– in terms of relapses, disability progression, other MRI metrics of inflammation
and MRI changes suggestive of ongoing neurodegeneration. No difference in the rate
and nature of adverse events was observed between the two treatment groups.
Conclusion
Although the study drop-out rate was too high to allow definite conclusions, our findings
suggest that curcumin might add to IFN β-1a efficacy on radiological signs of inflammation
in MS, while it did not seem to exert any neuroprotective effect as assessed by clinical
and MRI parameters. (NCT01514370)
Keywords
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Article info
Publication history
Published online: September 20, 2021
Accepted:
September 19,
2021
Received in revised form:
September 7,
2021
Received:
August 17,
2021
Identification
Copyright
© 2021 Elsevier B.V. All rights reserved.
