Data suggest early diagnosis and treatment have positive effects on clinical outcomes

Over decades of successive multiple sclerosis (MS) diagnostic criteria, patients who went from a first demyelinating event—so-called clinically isolated syndrome (CIS)—to MS were diagnosed and treated for MS earlier and were less likely to reach a milestone of accrued disability, a retrospective cohort study found.

Median times from initial CIS event to MS treatment decreased from 35.8 months in the earliest period in the study (1994-2000) to 6.6 months in the latest (2017-2020), an overall reduction of 82%, reported Mar Tintore, MD, PhD, of the Universitat Autònoma de Barcelona in Spain, and co-authors in Neurology.

Tintore and colleagues evaluated relapsing-remitting MS diagnoses during five diagnostic criteria periods: Poser (1994-2000) and four McDonald criteria (2001-2004, 2005-2009, 2010-2016, and 2017 to present), referred to as the first year of their respective applicability (e.g., McDonald 2005). All people in the study had CIS and were 18 or older.

The researchers found:

  • A higher proportion of MS diagnosed and treated patients were seen in more recent diagnostic criteria periods: overall, 62.6% were eventually diagnosed with MS, with an increase from 25.2% to 55.1% using earliest to latest criteria.
  • A sustained decrease in the time from CIS to MS diagnosis over the years; median time to MS diagnosis was 11.1 months with a 77% decrease in time to MS diagnosis.
  • Patients diagnosed in more recent diagnostic criteria periods had lower risk of reaching Expanded Disability Status Scale (EDSS) score of 3.0 or worse. The adjusted HR for reaching that score, using the earliest period (Poser) as a reference, was 0.47 for the second period, 0.25 for the third, 0.30 for the fourth, and 0.07 for the fifth period (McDonald 2017).
  • Improvement in disability outcome over time occurred, even when only the most recent diagnostic criteria (McDonald 2017) were used for all patients.

Tintore and colleagues studied 1,174 patients of age <50 years who were enrolled in the Barcelona-CIS cohort between January 1994 and March 2020. All participants had one otherwise unexplained episode suggestive of central nervous system demyelination (i.e., CIS).

When MS was diagnosed in a different period than the CIS episode, patients were classified as “catch up” patients and year of MS diagnosis was assigned as the first year of applicable criteria use (e.g., McDonald 2005 for those diagnosed between 2005-2009). The cohort was comprised of 68% women and median follow-up was 9.1 years.

Median age at time of CIS was 31.6 years, with a progressive increase in age at CIS diagnosis and at MS diagnosis over the course of the study. The median age at MS diagnosis was 33 years, and median age at MS diagnosis increased from 29 to 36 years from earliest to latest criteria.

If MS treatment began prior to a second episode suggestive of demyelination, it was considered early, otherwise, late. Treatment was early in 22.5% and late in 25%; the remainder received no treatment. Median time from CIS onset to treatment was 5.9 months in the early and 24 months in the late group. Early treatment was independently associated with lower risk of reaching EDSS of 3 or more (HR 0.53, 95% CI 0.33-0.85).

“A sustained increase both in the proportion of diagnosed and treated patients was found across diagnostic criteria periods after excluding ’catch up’ patients,” the researchers noted. Median time to MS diagnosis decreased overall from a 77% reduction to a 63% reduction across time periods when catch up patients were excluded.

“These data suggest that both early diagnosis and early treatment of MS have a positive effect on clinical outcome,” noted Oliver Tobin, MB, BCh, BAO, PhD, of the Mayo Clinic, in Rochester, Minnesota, in an accompanying editorial.

“It is challenging to disentangle the effect of high efficacy disease-modifying therapies on the outcome of this analysis; however, the analyses all point in the same direction—early diagnosis and treatment of MS results in lower MS-associated disability,” he added.

Over half of the cohort did not receive any treatment over the study period, and patients who did receive treatment tended to have markers of more aggressive disease, Tobin pointed out.

“Therefore, although we can conclude that as a group, patients with relapsing-onset MS are likely best served by early treatment, this does not discount the existence of patients for whom disease modifying therapies may confer no benefit or possibly even pose harm (so called benign MS),” he wrote. “The question as to whether long-term side effects of high-efficacy disease-modifying therapies warrant their use over traditional ’platform therapies’ is not addressed by this study.”

Despite this limitation, “this study provides evidence that early and accurate diagnosis of MS is an important factor in disability outcomes and that recent iterations of MS diagnostic criteria, when appropriately used, have succeeded in the goal of early diagnosis,” Tobin added. “It also provides additional evidence that for most patients with relapsing-onset MS, early initiation of disease-modifying therapies improves outcome.”

“Diagnostic criteria influence how we count patients with MS, thus influencing what we see as the ultimate outcome of the disease and how payers allocate resources,” Tintore and colleagues observed.

“Trials reporting long-term outcomes report what amounts to a delayed-start design, as patients cannot remain randomized for the 10- to 20-year time period needed to determine the long-term efficacy of disease-modifying therapy on disability accrual,” they added. “For this reason, long-term, well-characterized population-based studies are essential in providing reliable data on the long-term effectiveness of disease-modifying therapy for the prevention of disability in patients with multiple sclerosis.”

Limitations of the study included its lack of pediatric patients; results are not applicable to pediatrics patients or to patients older than 50, the researchers said. The analysis also did not account for changes in lifestyle factors such as diet, exercise, smoking, vitamin D use, and obesity that may affect time to diagnosis, disease severity, and response to treatment, the editorialist noted.

  1. Over decades of successive multiple sclerosis (MS) diagnostic criteria, patients who went from a clinically isolated syndrome (CIS) event to MS were diagnosed and treated for MS earlier and were less likely to reach a milestone of accrued disability.

  2. The findings suggest early MS diagnosis and treatment have a positive effect on clinical outcomes, the editorialist noted.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This study was funded by the European Regional Development Fund and received support from Instituto Carlos III, Red Española de Esclerosis Múltiple, Ajuts per donar Suport als Grups de Recerca de Catalunya, and a grant from Biogen to Fundacio privada Cemcat for statistical analysis.

Tintore has received compensation for consulting services and speaking honoraria from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela-Bio, and Teva Pharmaceuticals.

Tobin receives research funding from the Mayo Clinic Center for MS and Autoimmune Neurology, Mallinckrodt Inc., and the National Institutes of Health.

Cat ID: 130

Topic ID: 82,130,730,130,36,192,925