Newly approved agents for relapsing remitting multiple sclerosis: how real-world evidence compares with randomized clinical trials?

ABSTRACT

Introduction

In recent years, many treatment options have become available for relapsing remitting MS. Randomized clinical trials and real-world studies are complementary sources of information, and together have the potential to offer a comprehensive understanding of the safety and efficacy profiles of each drug, a critical factor for a personalized management of the disease.

Areas covered

In this review, the authors provide an up-to-date review of both RCTs and real-world studies assessing the safety and efficacy profiles of recently developed disease-modifying drugs for relapsing remitting MS. These include fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab and ocrelizumab.

Expert opinion

From the authors’ review of the literature, the efficacy profiles resulted from RCTs were confirmed by observational studies with regard to the disease-modifying drugs considered. The magnitude of the effects on annualized relapse rates and MRI active lesions was generally even larger in the observational studies compared to RCTs. From the safety point of view, observational studies revealed new adverse events, mostly in the area of bacterial and opportunistic infections, not seen in the relative registration programme. This is a very important gain because it allows to elaborate appropriate strategies to prevent and handle the risks.

KEYWORDS:

• Multiple sclerosis
• phase IV clinical trials
• real-world
• disease-modifying treatments

Article highlights

• More than 20 treatments for relapsing-remitting MS are currently available.

• The authors reviewed the safety and efficacy data of recently developed disease-modifying drugs (fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab and ocrelizumab) coming from both randomized clinical trials and observational studies;

• For all the reviewed drugs, the efficacy profiles resulted from RCTs was confirmed by observational studies;

• Observational studies revealed new adverse events, mostly in the area of bacterial and opportunistic infections, not seen in the relative registration programme

• Randomized clinical trials and real-world studies together have the potential to offer a comphrensive understanding of the safety and efficacy profiles of each drug

Declaration of interest

G Comi has received personal compensation from outside the submitted work from Novartis, Teva Pharmaceutical Industries Ltd, Teva Italia Srl, Sanofi Genzyme, Genzyme Corporation, Genzyme Europe, Merck KGgA, Merck Seorno SpA, Celgene Group, Biogen Idec, Biogen Italia Srl, F. Hoffman-La Roche, Roche SpA, Almirall SpA, Forward Pharma, Medday and Excemed. G Dalla Costa has received funding for research, travel, and/or speaker honoraria from Biogen, Celgene, Merck, Novartis, Roche, and Teva. L Moiola has received honoraria for consulting services and/or speaking activities from Biogen, Roche, TEVA, Sanofi, Merck, Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no specific funding.