TY - JOUR

T1 - An update on combination therapies for multiple sclerosis

T2 - where are we now?

AU - Sorensen, Per Soelberg

AU - Magyari, Melinda

AU - Sellebjerg, Finn

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Humans

KW - Multiple Sclerosis/drug therapy

KW - Immunosuppressive Agents/therapeutic use

KW - Multiple Sclerosis, Relapsing-Remitting/drug therapy

KW - Glatiramer Acetate/therapeutic use

KW - Anti-Inflammatory Agents/therapeutic use

KW - Randomized Controlled Trials as Topic

U2 - 10.1080/14737175.2023.2289572

DO - 10.1080/14737175.2023.2289572

M3 - Review

C2 - 38058171

VL - 23

SP - 1173

EP - 1187

JO - Expert Review of Neurotherapeutics

JF - Expert Review of Neurotherapeutics

SN - 1473-7175

IS - 12

ER -