Author Topic: Refining the criteria for diagnosing SPMS  (Read 196 times)

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Offline agate

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Refining the criteria for diagnosing SPMS
« on: September 06, 2016, 02:38:31 pm »
From NEJM Journal Watch, September 6, 2016:

Quote
SUMMARY AND COMMENT | NEUROLOGY

August 31, 2016

Refining the Criteria for Diagnosing Secondary Progressive Multiple Sclerosis

Robert T. Naismith, MD Reviewing Lorscheider J et al., Brain 2016 Jul 7;
Investigators established a definition that identified secondary progression 3 years earlier than treating clinicians.

The diagnosis of secondary progressive multiple sclerosis (SPMS) is challenging and often made in retrospect. Investigators used the MSBase dataset to develop an objective measure that reflected long-term disease worsening. MSBase includes clinical data from more than 34,154 patients and 113 MS centers in 34 countries.

SPMS definitions were based on the following criteria: amount of Expanded Disability Status Scale (EDSS) worsening, minimum EDSS at progression, minimum pyramidal Functional System (FS) score at progression, time to confirmed progression, confirmation within the same FS that triggered the progression, relapse activity prior to progression event, and relapse activity after.

Of 17,356 patients with sufficient follow-up and complete data, SPMS was diagnosed in 2360 (14%). The best definition included:

~A 1-point EDSS worsening with EDSS ≤5.5 or a 0.5-point EDSS worsening with EDSS ≥6.0, in the absence of a relapse

~A minimum EDSS score of 4

~Pyramidal FS score of ≥2

~Confirmed worsening over ≥3 months, and

~Confirmation of worsening within the same FS as worsening onset.

This definition identified 18% of the patients as converting to SPMS. Among those with ≥5 years of follow-up after SPMS diagnosis by this definition, 78% had continuing disability worsening and 70% needed to use at least a cane to walk 100 m. This definition also enabled diagnosis 3 years earlier than a clinical diagnosis of SPMS by the treating physician.

Comment

This refinement of the SPMS research definition will increase the sensitivity and speed of the diagnosis compared with current clinical practice. Most patients who met these criteria continued worsening in subsequent years. Although the criteria may not be 100% specific (86% vs. 95% for clinician diagnosis), they help define a particular high-risk population. With possible therapies for progressive MS on the horizon, making an accurate diagnosis of primary and secondary MS will be increasingly important.

« Last Edit: September 07, 2016, 04:06:04 pm by agate »
MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.

Offline agate

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(ECTRIMS) An EDSS-based definition of SPMS
« Reply #1 on: September 18, 2016, 09:23:59 am »
More on how to classify SPMS, and this seems to be another study. It was presented as a poster session (#298) at the annual ECTRIMS conference (September 14-17, London), and several of the authors are well known in the MS research field:

Quote
An EDSS-based definition of secondary progressive multiple sclerosis

C. Diaz-Cruz1, A.S. Chua1, B.C. Healy1,2, N. Sattarnezhad1, B.I. Glanz1, H.L. Weiner1, T. Chitnis1,3

1Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, 2Biostatistics Center, 3Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital, Boston, MA, United States

Objective:

To assess the impact of different definitions of secondary progressive multiple sclerosis (SPMS) on clinical trial design.

Background:

Clinical trials and observational studies have used different definitions of SPMS. Expert consensus has defined SPMS as a phenotype “diagnosed retrospectively by a history of gradual worsening after an initial relapsing disease course”. However, a standardized definition of “gradual worsening” and the minimum time needed to confirm it is lacking.

Methods:

Patients in the Comprehensive Longitudinal Investigation of Multiple Sclerosis (MS) at the Brigham and Women's Hospital (CLIMB) with relapsing-onset MS were eligible.

We evaluated 9 definitions of SPMS using 3 expanded disability status scale (EDSS) score ranges (3-6.5, 3.5-6.5, 4-6.5) and 3 time intervals (12, 24, 36 months) during which the EDSS was required to remain within the specified range (screening phase). We also tested each definition only in patients with no relapses during the screening phase.

In order to simulate a 2-year clinical trial, patients satisfying any of the definitions with at least 2 years of follow-up after the screening phase were included in the analysis. For each definition, we calculated the proportion of patients experiencing confirmed disability worsening at 6 months (CDW6), defined as EDSS increase ≥1 if baseline EDSS≤5.5 or EDSS increase ≥0.5 if baseline EDSS≥6. We also calculated the proportion of patients who maintained the CDW6 for the remainder of follow up.

Results:

623 patients satisfied at least one definition of SPMS and 402 had at least 2 years of follow up (31% males, mean age at onset 34±11 years, mean disease duration 15±9 years). The percentage of patients experiencing CDW6 over two years ranged between 15-22%. In those experiencing CDW6, the proportion of patients maintaining the confirmed EDSS for all subsequent visits varied between 56-67%, 70-75% and 55-71% when the lowest EDSS in the screening phase was set to 3.0, 3.5 or 4.0, respectively (median (IQR) follow up after CDW6, 46 (65) months). Similar results were obtained when we excluded patients who had relapses during the screening phase.

Conclusions:

Regardless of the duration of the screening phase, a similar proportion of patients experienced CDW6 and maintained the EDSS score after the confirmed progression date. Our results indicate that it may be possible to reduce screening periods when recruiting patients for SPMS trials.

__________
Disclosure:

Camilo Diaz-Cruz received research support from Merck Serono and Google Life Sciences.
Alicia S. Chua has received research support from Google Life Sciences.
Brian C. Healy was on the Biogen Worldwide Medical Biostatistics Multiple Sclerosis Advisory Board and received grant support from Genzyme, Merck Serono, Novartis and Google Life Sciences.
Neda Sattarnezhad received research support from Merck Serono and Google Life Sciences.
Bonnie I. Glanz received research support from Merck Serono and Google Life Sciences.
Howard L. Weiner has received personal compensation for consulting, speaking activities and has served on the scientific advisory board of companies including Biogen Idec, Novartis, EMD Serono and Teva and research support from Google Life Sciences.
Tanuja Chitnis: Consulting for: Biogen-Idec, Novartis, Roche-Genetech. Advisory boards: Serves on advisory boards for pediatric clinical trials for Novartis and Genzyme-Sanofi. Research support: Serono, Biogen, Novartis, Google Life Sciences
MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.

 

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