An update on combination therapies for multiple sclerosis: where are we now?

Expert Rev Neurother. 2023 Jul-Dec;23(12):1173-1187. doi: 10.1080/14737175.2023.2289572. Epub 2023 Dec 15.

Abstract

Introduction: In theory, combination of two agents, which are suboptimal when given individually, may result in a significant increase in therapeutic effect. Combination therapies have proven particularly effective against infections such as HIV, cancer, and also chronic autoimmune diseases such as rheumatoid arthritis.

Areas covered: The authors review the literature, searching for randomized placebo-controlled or comparative, double-blind or investigator-blinded clinical trials, not including open label clinical trials, of treatment of multiple sclerosis (MS) with combination therapy or add-on therapy, including trials of induction therapy, trials for prevention of disease activity or worsening, amelioration of adverse effects, and treatment of relapses, and trials to increase remyelination.

Expert opinion: Combination of two platform therapies (Interferon-beta or glatiramer acetate) was without additional effect. Clinical trials with add-on, often applying repurposed drugs (e.g. simvastatin, atorvastatin, minocycline, estriol, cyclophosphamide, azathioprine, albuterol, vitamin D), have been negative, apart from monthly methylprednisolone that, however, had low tolerability. Combination therapy for neuroprotection/remyelination showed some interesting results, though we are still awaiting results of phase III trials. The results of combination of anti-inflammatory therapies have in general been disappointing. In the future, combination of new effective neuroprotective/remyelinating drugs and highly effective anti-inflammatory treatments may benefit people with MS.

Keywords: (5-8) Multiple sclerosis; add-on therapy; combination therapy; disease-modifying therapy; neuroprotective therapy; remyelinating therapy; treatment of disease activity; treatment of relapses.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Glatiramer Acetate / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Multiple Sclerosis* / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting* / drug therapy
  • Randomized Controlled Trials as Topic

Substances

  • Immunosuppressive Agents
  • Glatiramer Acetate
  • Anti-Inflammatory Agents