Post hoc results from the Phase 3 ASCLEPIOS I and II studies (NCT02792218; NCT02792231) showed that ofatumumab (Kesimpta; Novartis) was superior to teriflunomide (Aubagio; Sanofi Genzyme) on a number of outcomes, including annualized relapse rate (ARR) and confirmed disability worsening (CDW), in patients with newly diagnosed, treatment-naïve (RDTN) multiple sclerosis (MS).1
In total, those treated with the B-cell targeting agent had an ARR of 0.09, otherwise a 50% greater reduction than those on teriflunomide (rate ratio [RR], 0.50; 95% CI, 0.33-0.74; P <.001 in addition ofatumumab numerically reduced the risk of cdw at months by ci>P = 0.065) and CDW at 6 months by 46% (RR, 0.54; 95% CI, 0.30-0.98; P = 0.044) compared to teriflunomide.
Lead author Ludwig Kappos, MD, professor of neurology at the University of Basel, and colleagues concluded that “these results are consistent with those observed in the general ASCLEPIOS population and show that ofatumumab can delay worsening disability at the onset of MS”. They added that these data continue to support the use of ofatumumab as a first-line treatment for this patient population.
Of the 1882 participants randomly assigned to treatment in the original ASLCEPIOS trials, 615 (32.7%) were RDTN (ofatumumab, n=314; teriflunomide, n=301), with a range of 0.1 to 2.9 years from diagnosis for both groups. As expected, RDTN participants in both groups were younger, with lower disability scores and lower T2 lesion volume at the time of analysis compared to the overall ASCLEPIOS population. A total of 90% of participants were treated with either drug for at least 1 year, and 25% received treatment for more than 2 years.
An additional post-hoc endpoint observed in the RDTN population was progression independent of relapse activity (PIRA), considered in the absence of confirmed relapses during the study. Although more than half of all 3-month CDW events and 6-month CDW events that occurred in the 2 treatment groups were considered PIRA, the proportion of participants in the ofatumumab group with PIRA events over 3 months was numerically lower (6.6% versus 9.1%; RR, 0.55; 95% CI, 0.27-1.11; P = 0.096), and the proportion of PIRA events at 6 months was significantly lower (3.6% versus 7.7%; HR, 0.44; 95% CI, 0.20-1.00; P = 0.049) compared to those on teriflunomide.
At the end of the treatment period, ofatumumab reduced the mean number of gadolinium-enhancing T1 lesions per scan by 95% compared to teriflunomide (0.02 versus 0.39; RR, 0.05; CI 95%, 0.02-0.10; P <.001 similarly kappos et al also observed an difference in the reduction of new or expanding t2 lesions between groups however they found no annual percentage change brain volume.>
Comparing the 2 treatment groups in Year 1, Year 2, and through Year 2, a total of 47.0%, 92.1%, and 44.6% of patients treated with ofatumumab achieved no signs of disease activity (NEDA) status 3, respectively, compared to 24.7%, 46.8% and 17.7% of those on teriflunomide. Although the investigators did not observe a difference in serum neurofilament light (NfL) concentration at month 3, the NfL concentration was significantly lower in the ofatumumab group at month 12 (6.60 vs 8.61 pg /mL, ratio, 0.77, 95% CI, 0.71-0.83; P P <.001>
In terms of safety, both treatments had a similar proportion of patients with adverse events (AEs), as well as serious AEs. Notably, no deaths, birth defects, or congenital malformations have been reported in people in either group exposed to the treatment during pregnancy. Neutropenia, a known risk associated with teriflunomide, occurred in 4 participants treated with teriflunomide versus 2 in the ofatumumab group. Additionally, both groups experienced a similar rate of infections (ofatumumab, 56.1%; teriflunomide, 56.5%), with 6 participants (1.9%) in the ofatumumab group and 2 (0.7% ) in the teriflunomide group with serious infections.
For those treated with ofatumumab, sub-lower limit of normal (LLN) B-cell depletion of 40 cells/µL was achieved in 97% of patients at week 2, which remained constant through end of the test. Additionally, 90% and 98% of ofatumumab-treated patients had B-cell depletion of less than or equal to 10 cells/µL at week 4 and week 12, respectively. After the last dose of ofatumumab in participants who discontinued treatment for any reason, B cell repletion (levels above the LIN) was observed in 12 of 27 participants (44%) at week 24, 13 of 21 (62%) at Week 36, 6 of 8 (75%) at Week 48, and 8 of 8 (100%) at Week 60.