How can Big Data be used in the field of multiple sclerosis? And what’s the latest on existing treatment options? The ECTRIMS congress in Berlin clarified.
Big MS Data (BMSD) Network represents a collaboration of the national MS registries of Denmark, Italy and Sweden, as well as MSBase and OFSEP (France). A cohort of 11 871 patients from this network has now been used to evaluate when to start disease-modifying therapy (DMT) to prevent longer-term disability accumulation [1]. Starting DMT within six months of disease onset proved optimal in this regard.
Also He et al. have used data from the MSBase registry and two local registries for a similar analysis [2]. They found that there was less disability accumulation in patients treated with high-potency therapy (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, natalizumab) early after diagnosis.
5-year data on ocrelizumab
In Berlin, many data on already approved therapeutic options were presented, including 5-year data on ocrelizumab in patients with relapsing-remitting MS (OPERA I and II studies) [3,4]. They showed that there was a rapid reduction in annual relapse rate (ARR) in patients who were switched from interferon β-1a to ocrelizumab after the two-year double-blind open-label extension (OLE) phase (“switchers”) [3]. Both in these “switchers” and in patients who had already received ocrelizumab in the double-blind phase (“OCR-OCR”), the achieved reduction in ARR was maintained into year 5. Compared with the “switchers,” the “OCR-OCR” patients also achieved a significant and sustained reduction in disability progression into year 5.
After the change in therapy, the switchers further experienced a robust and sustained reduction in disease activity (Gd+ T1 and new/enhancing T2 lesions) assessed by MRI until year 5 [4]. In the “OCR-OCR” group, the near-complete suppression of Gd+-T1 lesions achieved in the double-blind phase was maintained during OLE. The low number of new/enlarging T2 lesions also remained stable. Finally, after five years of therapy, patients initially randomized to ocrelizumab showed less brain matter loss than “switchers” (total brain volume and white and cortical gray matter).
Interferon β-1a vs. fingolimod in pediatric MS.
At this year’s ECTRIMS, the topic of pediatric MS was also on the agenda at several points. For example, in a Scientific Session, Brenda Banwell, MD, Philadelphia, presented data from the phase III PARADIGMS trial, the first completed active-controlled trial designed specifically for pediatric MS patients [5]. Ten- to 17-year-old patients received either 0.5 mg fingolimod per day (or 0.25 mg/d in patients ≤40 kg body weight) or 30 μg interferon (IFN) β-1a i.m. once weekly. Finally, there was a significant 82% reduction in ARR with fingolimod compared with IFN β-1a. MRI-detectable disease activity and acute inflammatory lesion volume were also significantly reduced by fingolimod compared with IFN β-1a. Brain atrophy rate significantly reduced by 40% on fingolimod. The safety profile of fingolimod in pediatric patients was consistent with that in adults [6]. The overall rate of adverse events was higher with IFN β-1a than with fingolimod (95.3% vs. 88.8%). Serious adverse events occurred in 16.8% of patients receiving fingolimod and 6.5% of patients receiving IFN β-1a.
Primary analysis of the phase II study with evobrutinib
Xavier Montalban, MD, Barcelona, presented the primary analysis of the phase II trial of the BTK inhibitor evobrutinib in the Late Breaking News Session [7]. BTK plays a central role in various adaptive and innate immune system processes relevant in the pathogenesis of MS. The placebo-controlled study now evaluated different doses of evobrutinib (25 mg QD, 75 mg QD, 75 mg BID) over a 24-week period. As shown, 75 mg QD and 75 BID resulted in a significant reduction in Gd+ T1 lesions vs. placebo. In addition, there was a trend toward a reduction in ARR. Overall, the treatment was well tolerated. Increases in several laboratory parameters (ALT, AST, lipase) were noted, particularly in the 75 mg evobrutinib BID group. However, these were reversible and asymptomatic. None of the three doses resulted in severe infections or lymphopenias. This is the first time that a BTK inhibitor has been shown to reduce disease activity in a randomized trial. The current study will now continue for another 24 weeks.
Source: ECTRIMS Congress, October 10-12, 2018, Berlin (D).
Literature:
- Iaffaldano P, et al: The optimal time to start treatment in relapsing remitting multiple sclerosis patients: results from the Big Multiple Sclerosis Data Network. Ectrims 2018; Abstract 204.
- He A, et al: Early start of high-efficacy therapies improves disability outcomes over 10 years. Ectrims 2018, Abstract P919.
- Hauser SL, et al: Long-term reduction of relapse rate and confirmed disability progression after 5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis. Ectrims 2018; Abstract P590.
- Arnold DL, et al: Long-term reduction in brain MRI disease activity and atrophy after 5 years of Ocrelizumab treatment in patients with relapsing multiple sclerosis. Ectrims 2018; Abstract P588.
- Chitnis T, et al: Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis. N Engl J Med 2018; 379: 1017-1027.
- Arnold D, et al: Effects of Fingolimod on MRI Outcomes in Patients with Pediatric Onset Multiple Sclerosis: Results from Phase 3 PARADIGMS Study. AAN 2018; Abstract S51.005.
- Montalban X, et al: Primary analysis of a randomised,
- placebo-controlled, phase 2 study of the Bruton’s tyrosine kinase inhibitor evobrutinib (M2951) in patients with relapsing multiple sclerosis. Ectrims 2018; Abstract 322.
Further reading:
- Torke S, et al: Inhibition of Bruton’s tyrosine kinase selectively prevents antigen-activation of B cells and ameliorates B cell-mediated experimental autoimmune encephalomyelitis. Ectrims 2018; Abstract P575.
InFo NEUROLOGY & PSYCHIATRY 2018; 16(6): 58-59.
