Which Therapies Offer the Lowest Relapse Rates in Early MS?

B cell-depleting therapies (BCDTs) might lead to fewer relapses and lower brain lesion volume than oral therapies in people newly diagnosed with multiple sclerosis (MS), a new prospective study showed.In the analysis of more than 500 adults with no history of disease-modifying therapy (DMT), BCDTs were associated with a 62% lower relapse rate and lower T2 brain lesion volume vs oral platform therapies over 2 years. Treatment adherence was also higher with BCDTs, with 94% of patients staying on their initial therapy at 2 years.Despite these differences in inflammatory disease activity, treatment strategies did not differ significantly in disability and serum neurofilament light chain (sNfL), a blood biomarker of nerve cell injury.“These findings may help doctors and people with MS talk about what to expect from early treatment,” investigator Fredrik Piehl, MD, PhD, professor at Karolinska Institutet in Stockholm, Sweden, said in a statement. “No single treatment will be the best choice for everyone, and patient characteristics need to be considered when selecting therapy.”The study was published online on September 9 in Neurology Open Access.Early Treatment StrategiesMS is a chronic autoimmune disease characterized by inflammation, demyelination, and neurodegeneration. Although DMTs have expanded treatment options, the optimal strategy for initiating therapy remains unclear.Much of what is known about the drugs’ efficacy comes from randomized trials that typically enroll only select patients and operate under controlled conditions, which may not reflect the range of patients and treatment decisions clinicians encounter in everyday practice.With few prospective international studies looking at both MRI findings and blood biomarkers in early MS, investigators of the Pan-European MultipleMS Study compared 2-year clinical, radiologic, and biomarker outcomes across DMTs in treatment-naive patients with newly diagnosed MS using standardized follow-up.The investigators also examined sNfL and serum glial fibrillary acidic protein (sGFAP), a marker of glial activation that has been associated with chronic inflammation and progression independent of relapse activity.The prospective, multicenter observational study comprised 509 adults (mean age, 33 years; 63.9% women) with newly diagnosed MS who were recruited between September 2017 and December 2020 at centers in Belgium, Denmark, Germany, Italy, Norway, Spain, and Sweden.Participants were classified according to the initial DMT started within 6 months of study entry: injectable platform therapies (interferon-beta and glatiramer acetate; 17.1%), oral platform therapies (dimethyl fumarate and teriflunomide; 29.9%), high-efficacy therapies (fingolimod, cladribine, natalizumab, and alemtuzumab; 15.5%), BCDTs (rituximab and ocrelizumab; 19.8%), or no treatment (17.7%).Investigators used the oral therapy cohort as the reference group, noting that it included the most participants and represented moderate efficacy.Participants underwent standardized clinical assessments, MRI, and blood biomarker testing, and 89.4% completed the 2-year follow-up.Primary outcomes included the annualized relapse rate (ARR), change in T2 lesion volume, and sNfL Z-score at 24 months. Secondary outcomes included T2 lesion count, sGFAP Z-score, change in Expanded Disability Status Scale (EDSS), and adherence with the initial DMT.Because treatment was not randomly assigned, investigators adjusted analyses for baseline factors including age, sex, disease duration, MS phenotype, prior-year relapse rate, EDSS, lesion volume, sNfL, sGFAP, and country.Fewer Relapses, Less Lesion GrowthMost participants had relapsing MS (n = 486), 22 had primary progressive MS, and one had secondary progressive MS. The median disease duration was 0.66 years, and the median baseline EDSS score was 1.5.Compared to the oral therapy group, those taking BCDTs had the lowest ARR (0.04 vs 0.16) and a 62% lower relapse rate (adjusted incidence rate ratio, 0.38; 95% CI, 0.15-0.92).High-efficacy therapies also had fewer relapses than the reference group (0.11 vs 0.16), although the difference was not statistically significant. Injectable therapies were associated with the highest relapse rate (ARR, 0.21).MRI findings showed a similar pattern. Compared with oral platform therapies, BCDTs were associated with a modest reduction in T2 lesion volume (volume ratio, 0.87; 95% CI, 0.76-0.99). High-efficacy therapies had the largest median reduction in lesion volume at 24 months (-0.35 mL) compared to those taking oral treatments, but the difference was not statistically significant.There were no significant differences between treatment groups in changes in EDSS or sNfL at 2 years.Meanwhile, the largest sGFAP decline was reported in patients who received oral platform therapies. However, levels remained higher in patients who received high-efficacy therapies and BCDTs, although adjusted between-group differences were not significant.Treatment adherence also differed across treatment groups at 24 months, with the highest rate with BCDTs (93.8%), followed by high-efficacy therapies (86.5%), oral platform therapies (72.3%), and injectable platform therapies (60.8%).After adjustment, BCDTs were associated with about five times higher odds of remaining on the initial treatment than oral platform therapies (adjusted odds ratio [OR], 4.88; 95% CI, 1.56-15.31). More than half of initially untreated patients subsequently started a DMT.What the Data May Not CaptureTreatment groups differed most in measures of acute inflammatory activity, whereas disability and blood biomarkers showed a less clear pattern over the first 2 years.“While this possibly reflects the short study follow-up, it may likely reveal the poor sensitivity to change of the EDSS,” Carmen Tur, MD, PhD, a neurologist and clinical neuroimmunology researcher at Vall d’Hebron Institut de Recerca in Barcelona, Spain, wrote in an accompanying editorial.Tur also noted that patient-reported and patient-administered measures of neurologic function may be more sensitive for detecting progression.The biomarker findings offered another perspective. sGFAP levels decreased most in the oral platform group, while levels remained relatively higher among patients who received high-efficacy therapies and BCDTs. There were no significant differences between groups in sGFAP at 2 years. This pattern may point to differences in chronic inflammation that are not captured by measures of acute disease activity, Tur suggested.“Taken together, these results underscore an unmet therapeutic need and support the concept that chronic CNS [central nervous system] compartmentalized inflammation evolves largely independently of acute inflammatory activity,” she wrote.Whether the differences seen in relapses and MRI activity will translate into differences in disability or other clinically meaningful outcomes remains uncertain, particularly given the short follow-up, Tur added.Disclosure information for study authors is available in the original study publication. Tur reported receiving honoraria from Roche, Novartis, Merck, Sanofi, Immunic Therapeutics, and Bristol Myers Squibb.