Current and Emerging Therapies in Multiple Sclerosis: Implications for the Radiologist, Part 2—Surveillance for Treatment Complications and Disease Progression

Abstract

SUMMARY: An understanding of the new generation of MS drugs in conjunction with the key role MR imaging plays in the detection of disease progression, opportunistic infections, and drug-related adverse effects is of vital importance to the neuroradiologist. Part 1 of this review outlined the current treatment options available for MS and examined the mechanisms of action of the various medications. It also covered specific complications associated with each form of therapy. Part 2, in turn deals with the subject of pharmacovigilance and the optimal frequency of MRI monitoring for each individual patient, depending on his or her unique risk profile. Special attention is given to the diagnosing of progressive multifocal leukoencephalopathy in patients treated with natalizumab as this is a key area in which neuroradiologists can contribute to improved patient outcomes. This article also outlines the aims of treatment and reviews the possibility of "no evidence of disease activity" becoming a treatment goal with the availability of more effective therapies. Potential future areas and technologies including image subtraction, brain volume measurement and advanced imaging techniques such as double inversion recovery are also reviewed. It is anticipated that such advancements in this rapidly developing field will improve the accuracy of monitoring an individual patient's response to treatment. ABBREVIATIONS:BV ϭ brain volume; DIR ϭ double inversion recovery; DMT ϭ disease-modifying therapy; IRIS ϭ immune reconstitution inflammatory syndrome;

Depletion of PD-1-positive cells ameliorates autoimmune disease

“…PD-1 + cell depletion preserves normal adaptive immunity, which sharply contrasts from the generalized immune deficiency caused by currently available immune suppressants 6,[9][10][11][12]46 . It is acknowledged that PD-1 + cell depletion could diminish non-autoreactive PD-1 + lymphocytes including PD-1 + effector cells and Tregs 49 .…”

“…The αPD-1-ABD-PE treatment did not cause lymphopenia that is often associated with therapeutics for autoimmune diseases 6,[9][10][11][12]46 . We compared the B220+, CD4+ and CD8+ lymphocytes in blood and spleens of C57BL/6 mice ( Figure 6a) after mice received one dose of 1) αPD-1-ABD-PE, 2) PBS, 3) a mixture of αPD-1 and ABD-PE, or 4) cyclophosphamide (CP).…”

“…Targeted suppression of certain lymphocyte populations is an effective strategy to treat the diseases that has yielded new therapies for multiple sclerosis (MS) and systemic lupus erythematosus (SLE) [5][6][7][8] . However, these therapies are rarely considered as first-line therapeutic options due to their indiscriminate inhibition of normal adaptive immunity 6,[9][10][11][12] . This inhibition occurs because these therapies target lymphocytes too broadly [4][5][6]11 .…”

Mechanisms and therapeutic strategies of immune checkpoint molecules and regulators in type 1 diabetes

“…Although T1D is considered one of the annoying side effects induced by immune checkpoint inhibitors, immune checkpoint molecules exhibit the potential as a therapeutic maneuver for T1D control ( 20 , 89 , 94 ). In general, inhibition of autoreactive lymphocyte populations is considered an effective therapeutic strategy for the treatment of autoimmune diseases including T1D, but its clinical application is limited due to the massive suppression of lymphocytes involved in normal adaptive immunity ( 17 , 95 , 96 ). Therefore, targeted inhibition of pathogenic lymphocytes associated with autoimmune diseases generated considerable clinical interest ( 97 , 98 ).…”

The effect of combining PD-1 agonist and low-dose Interleukin-2 on treating systemic lupus erythematosus

“…Zhao P et al. established three groups of models (spontaneous T1D model disease delay study, cyclophosphamide (CP) accelerated T1D model disease delay study and α PD-1 accelerates T1D mode disease delay research) and showed that PD-1 + not only helped to control autoimmune diseases, but also maintained the normal adaptive immunity of the body ( 31 , 83 , 84 ).Therefore, we speculated that PD-1 agonists might be able to achieve specific inhibition of highly activated immune cells through PD-1 inhibition signals.…”