This year marks the centenary of two important events in medicine. In January of 1922, Frederick Banting became the first to successfully treat diabetes with intravenous insulin. (Nicolae Paulescu was less celebrated for opting for the rectal route and is now better known as the founder of a Romanian fascist party.)
The second event was the publication of the Association for Research in Nervous and Mental Disease (ARNMD) monograph on multiple sclerosis (disseminated sclerosis). ARNMD was the International Working Group or Canadian Working Group of its day. Following a two-day meeting in December 1921, ARNMD provided the first comprehensive summary of what was known about MS. Group members were fairly certain that MS was not bacterial in origin but were unsure if MS was an inflammatory or neurodegenerative disease.
ARNMD’s first monograph a year before addressed the outbreak of encephalitis lethargica following the Spanish flu pandemic. The fourth wave of the pandemic had finally petered out a year before after infecting some 500 million people. The estimated death toll in the U.S. was 800,000.
Tragically, the U.S. surpassed that grim milestone in 2021: more Americans have now died of COVID-19 than the Spanish flu. In the coming year, the number of COVID-19 cases worldwide (currently 329 million) will likely surpass the number of Spanish flu cases. To date, Canada has seen 31,530 COVID deaths (vs. 50,000 from Spanish flu). Fortunately, the global case-mortality rate for COVID (1.7%) is less than one-half of what was seen with Spanish flu.
The latest wave of COVID-19 began in November with detection of the variant dubbed Omicron (next up is Pi, which is irrational and a constant). So we are likely to see a new round of studies on vaccine efficacy against Omicron this year. Clinicians can also expect to see updated data on the safety of COVID vaccinations in pregnancy. A preliminary analysis of the U.S. Vaccine Adverse Event Reporting System reported no apparent safety signals (Shimabukuro et al. N Engl J Med 2021; 384:2273-2282). Also anticipated are new data from the ongoing phase II/III trial of COVID-19 vaccination in children aged 5-11 years (Walter et al. N Engl J Med 2022;386:35-46; free full text at www.ncbi.nlm.nih.gov/pmc/articles/PMC8609605/pdf/NEJMoa2116298.pdf).
This year should see additional data on COVID-19 outcomes in MS patients from the Global Data Sharing Initiative and other databases. Of particular interest would be more details about the higher mortality rate that was reported at last year’s ECTRIMS meeting (Prosperini et al. P759. Evangelou et al. P142). MS databases should also provide more information on COVID-19 outcomes with DMTs of interest, such as the anti-CD20s and S1PR agonists.
The pandemic has focussed attention on the safety of anti-CD20 therapies and new data should clarify two areas of special interest. There are preliminary data indicating that patients receiving an anti-CD20 agent can mount a robust spike-specific CD4+ and CD8+ T cell response (Madelon et al. Clin Infect Dis 2021; epublished November 17, 2021); more data will be forthcoming. Secondly, it appears that anti-CD20 agents have differing effects on serum immunoglobulin levels. Expect an update on the impact of ofatumumab on serum Ig levels; initial data were presented at last year’s ECTRIMS (Wiendl et al. P931).
Vaccine safety will continue to be a concern as an increasing number of MS patients get their booster shots. A third dose is of particular importance for MS patients on high-efficacy DMTs (e.g. Ocrevus) who likely had a suboptimal vaccine response to the two-dose regimen. The Canadian Network of MS Clinics has not provided any guidance on the timing of booster shots but may do so yet. As of January, the booster program was well underway and 33% of Canadians had already received their third dose (https://globalnews.ca/news/8492863/covid-19-vaccine-and-booster-tracker-coronavirus-canada/).
January 2022 saw the approval of the first in-home treatment for COVID-19. Paxlovid (nirmatrelvir + ritonavir) is an antiviral cocktail that reduced severe COVID outcomes by 89% versus placebo when administered within three days of symptom onset, according to the phase II/III EPIC-HR trial. However, the supply appears to be limited and access is likely to be a problem.
A number of studies may post results this year. Of interest are the phase IV DISCOMS study of DMT discontinuation, the KYRIOS study of COVID-19 in patients receiving ofatumumab, and the phase III trial of the tyrosine kinase inhibitor masitinib in SPMS. We may also see interim results from the two early high-efficacy DMT trials (TREAT-MS, DELIVER-MS), from the RIDOSE-MS trial of low-dose rituximab and the trial of high-dose ocrelizumab. The century-old discussion about the role of inflammation and neurodegeneration in MS progression is unlikely to be resolved but will doubtless continue.