Correction: Association Between Body Mass Index and Response to Disease-Modifying Therapies in Patients With Relapsing-Remitting Multiple Sclerosis at King Abdulaziz University Hospital: A Retrospective Study.

[This corrects the article DOI: 10.7759/cureus.32695.].

Association Between Body Mass Index and Response to Disease-Modifying Therapies in Patients With Relapsing-Remitting Multiple Sclerosis at King Abdulaziz University Hospital: A Retrospective Study.

Background Multiple sclerosis (MS) is an immune-mediated inflammatory disease that attacks myelinated axons in the central nervous system, destroying the myelin and axon to varying degrees and producing significant physical disability. So far, many studies have found that having a high body mass index (BMI) is associated with severe autoimmune and neurodegenerative disease course. However, the impact of BMI on disease-modifying therapy (DMT) response in terms of decreasing relapses and improving overall health remains unknown. Aims and objectives The study aimed to demonstrate the effect of BMI on DMT responsiveness in patients with relapse-remitting MS at a tertiary hospital. Methods and material A single-center retrospective study was conducted at a tertiary care center in Jeddah, Saudi Arabia. The study included 89 individuals with relapsing-remitting MS who had their BMI measured within six months of their first clinical relapse, as well as their clinical response to the DMT (number of relapses on a single DMT after six months of initiation) and MRI changes (development of new T2 lesions or gadolinium-enhancing lesions on single DMT six months after DMT initiation). Results Demographic data revealed a female predominance of 71.9%, and 51.7% of the patients had a normal weight. The most commonly prescribed DMT was Gilenya at 47.2%. A significant relationship was found between BMI and the total number of clinical relapses (p=0.038), with the co-existence of a positive correlation between BMI and the number of relapses after at least six months of initiation of DMT. Additionally, MS patients who had both positive MRI changes and obesity had a significantly higher BMI mean than non-obese. Conclusion Increased BMI appeared to be associated with a lower response to DMT, as overweight patients had a worse course than normal and underweight patients. Pharmacokinetic differences are the most likely factors implicated in medication responsiveness.

Sphingosine 1-Phosphate Receptor Modulators for Multiple Sclerosis.

Fingolimod (Gilenya) received regulatory approval from the US FDA in 2010 as the first-in-class sphingosine 1-phosphate (S1P) receptor (S1PR) modulator and was the first oral disease-modifying therapy (DMT) used for the treatment of the relapsing forms of multiple sclerosis (MS). Development of this new class of therapeutic compounds has continued to be a pharmacological goal of high interest in clinical trials for treatment of various autoimmune disorders, including MS. S1P is a physiologic signaling molecule that acts as a ligand for a group of cell surface receptors. S1PRs are expressed on various body tissues and regulate diverse physiological and pathological cellular responses involved in innate and adaptive immune, cardiovascular, and neurological functions. Subtype 1 of the S1PR (S1PR1) is expressed on the cell surface of lymphocytes, which are well known for their major role in MS pathogenesis and play an important regulatory role in the egress of lymphocytes from lymphoid organs to the lymphatic circulation. Thus, S1PR1-directed pharmacological interventions aim to modulate its role in immune cell trafficking through sequestration of autoreactive lymphocytes in the lymphoid organs to reduce their recirculation and subsequent infiltration into the central nervous system. Indeed, receptor subtype selectivity for S1PR1 is theoretically favored to minimize safety concerns related to interaction with other S1PR subtypes. Improved understanding of fingolimod's mechanism of action has provided strategies for the development of the more selective second-generation S1PR modulators. This selectivity serves to reduce the most important safety concern regarding cardiac-related side effects, such as bradycardia, which requires prolonged first-dose monitoring. It has led to the generation of smaller molecules with shorter half-lives, improved onset of action with no requirement for phosphorylation for activation, and preserved efficacy. The shorter half-lives of the second-generation agents allow for more rapid reversal of their pharmacological effects following treatment discontinuation. This may be beneficial in addressing further treatment-related complications in case of adverse events, managing serious or opportunistic infections such as progressive multifocal leukoencephalopathy, and eliminating the drug in pregnancies. In March 2019, a breakthrough in MS treatment was achieved with the FDA approval for the second S1PR modulator, siponimod (Mayzent), for both active secondary progressive MS and relapsing-remitting MS. This was the first oral DMT specifically approved for active forms of secondary progressive MS. Furthermore, ozanimod received FDA approval in March 2020 for treatment of relapsing forms of MS, followed by subsequent approvals from Health Canada and the European Commission. Other second-generation selective S1PR modulators that have been tested for MS, with statistically significant data from phase II and phase III clinical studies, include ponesimod (ACT-128800), ceralifimod (ONO-4641), and amiselimod (MT-1303). This review covers the available data about the mechanisms of action, pharmacodynamics and kinetics, efficacy, safety, and tolerability of the various S1PR modulators for patients with relapsing-remitting, secondary progressive, and, for fingolimod, primary progressive MS.