DMTs Reduce the Risk of Conversion to Secondary Progressive MS

PARIS—Secondary progressive multiple sclerosis (MS) is at least partly a consequence of early inflammation, and the risk of conversion from relapsing-remitting MS to secondary progressive MS is modifiable over five years with existing disease-modifying therapies (DMTs), according to research described at the Seventh Joint ECTRIMS–ACTRIMS Meeting. High-efficacy therapies such as alemtuzumab and natalizumab reduce the risk to a greater extent than do other DMTs.

Current immunotherapies do not slow secondary progressive MS after disease onset. The extent to which secondary progressive MS reflects early inflammation is not certain. Also unclear is whether conversion to secondary progressive MS might be modified by immunomodulatory DMTs during the relapsing-remitting phase.

Using an objective definition of secondary progressive MS published by Lorscheider et al in 2016, J. William L. Brown, MD, of the Queen Square MS Center at University College of London Institute of Neurology, and colleagues examined whether DMTs delay or reduce conversion from relapsing-remitting MS to secondary progressive MS. They examined patients with relapsing-remitting MS who participated in the MSBase database and were treated with a single DMT with at least four years of on-treatment follow-up. In all, 240 patients received injectables (ie, interferons or glatiramer acetate), 109 took fingolimod, 93 received natalizumab, and 44 took alemtuzumab.

Participants were each propensity matched to untreated patients with relapsing-remitting MS from a historical cohort (n = 622; mean follow-up, 9.2 years) and then matched to different DMT groups. Patients were matched on gender, baseline age, annualized-relapse rate, Expanded Disability Status Scale (EDSS) score, and disease duration. The researchers used weighted conditional proportional hazards models adjusted for EDSS frequency with pairwise censoring to compare the proportions of patients in each group who were free from conversion to secondary progressive MS.

Because lower-efficacy drug groups may have been biased towards participants with milder disease through excluding patients with multiple DMTs (such as treatment escalators), the investigators limited the injectables group to patients followed up before higher-efficacy drugs became available in 2006.

All DMTs reduced the hazard of conversion to secondary progressive MS, compared with different groups of matched untreated patients, in a series of pairwise analyses. For injectables, the hazard ratio (HR) of conversion to secondary progressive MS was 0.31 (median censored on-treatment follow-up, 7.9 years). For fingolimod, the HR was 0.23 (follow-up, 4.6 years). Natalizumab was associated with an HR of 0.50 (follow-up, 4.9 years). Alemtuzumab had an HR of 0.60 (follow-up, 7.2 years).

When the investigators matched patients between the treated cohorts, they found no significant difference in rate of conversion to secondary progressive MS between alemtuzumab and natalizumab. Alemtuzumab and natalizumab were therefore combined in a category of high-efficacy therapies (n = 118) and matched and compared with the injectables group (n = 236). High-efficacy therapies conferred greater protection against conversion to secondary progressive MS than injectables did (HR, 0.65; follow-up, 5.7 years).

PARIS—Secondary progressive multiple sclerosis (MS) is at least partly a consequence of early inflammation, and the risk of conversion from relapsing-remitting MS to secondary progressive MS is modifiable over five years with existing disease-modifying therapies (DMTs), according to research described at the Seventh Joint ECTRIMS–ACTRIMS Meeting. High-efficacy therapies such as alemtuzumab and natalizumab reduce the risk to a greater extent than do other DMTs.

Current immunotherapies do not slow secondary progressive MS after disease onset. The extent to which secondary progressive MS reflects early inflammation is not certain. Also unclear is whether conversion to secondary progressive MS might be modified by immunomodulatory DMTs during the relapsing-remitting phase.

Using an objective definition of secondary progressive MS published by Lorscheider et al in 2016, J. William L. Brown, MD, of the Queen Square MS Center at University College of London Institute of Neurology, and colleagues examined whether DMTs delay or reduce conversion from relapsing-remitting MS to secondary progressive MS. They examined patients with relapsing-remitting MS who participated in the MSBase database and were treated with a single DMT with at least four years of on-treatment follow-up. In all, 240 patients received injectables (ie, interferons or glatiramer acetate), 109 took fingolimod, 93 received natalizumab, and 44 took alemtuzumab.

Participants were each propensity matched to untreated patients with relapsing-remitting MS from a historical cohort (n = 622; mean follow-up, 9.2 years) and then matched to different DMT groups. Patients were matched on gender, baseline age, annualized-relapse rate, Expanded Disability Status Scale (EDSS) score, and disease duration. The researchers used weighted conditional proportional hazards models adjusted for EDSS frequency with pairwise censoring to compare the proportions of patients in each group who were free from conversion to secondary progressive MS.

Because lower-efficacy drug groups may have been biased towards participants with milder disease through excluding patients with multiple DMTs (such as treatment escalators), the investigators limited the injectables group to patients followed up before higher-efficacy drugs became available in 2006.

All DMTs reduced the hazard of conversion to secondary progressive MS, compared with different groups of matched untreated patients, in a series of pairwise analyses. For injectables, the hazard ratio (HR) of conversion to secondary progressive MS was 0.31 (median censored on-treatment follow-up, 7.9 years). For fingolimod, the HR was 0.23 (follow-up, 4.6 years). Natalizumab was associated with an HR of 0.50 (follow-up, 4.9 years). Alemtuzumab had an HR of 0.60 (follow-up, 7.2 years).

When the investigators matched patients between the treated cohorts, they found no significant difference in rate of conversion to secondary progressive MS between alemtuzumab and natalizumab. Alemtuzumab and natalizumab were therefore combined in a category of high-efficacy therapies (n = 118) and matched and compared with the injectables group (n = 236). High-efficacy therapies conferred greater protection against conversion to secondary progressive MS than injectables did (HR, 0.65; follow-up, 5.7 years).

PARIS—Secondary progressive multiple sclerosis (MS) is at least partly a consequence of early inflammation, and the risk of conversion from relapsing-remitting MS to secondary progressive MS is modifiable over five years with existing disease-modifying therapies (DMTs), according to research described at the Seventh Joint ECTRIMS–ACTRIMS Meeting. High-efficacy therapies such as alemtuzumab and natalizumab reduce the risk to a greater extent than do other DMTs.

Current immunotherapies do not slow secondary progressive MS after disease onset. The extent to which secondary progressive MS reflects early inflammation is not certain. Also unclear is whether conversion to secondary progressive MS might be modified by immunomodulatory DMTs during the relapsing-remitting phase.

Using an objective definition of secondary progressive MS published by Lorscheider et al in 2016, J. William L. Brown, MD, of the Queen Square MS Center at University College of London Institute of Neurology, and colleagues examined whether DMTs delay or reduce conversion from relapsing-remitting MS to secondary progressive MS. They examined patients with relapsing-remitting MS who participated in the MSBase database and were treated with a single DMT with at least four years of on-treatment follow-up. In all, 240 patients received injectables (ie, interferons or glatiramer acetate), 109 took fingolimod, 93 received natalizumab, and 44 took alemtuzumab.

Participants were each propensity matched to untreated patients with relapsing-remitting MS from a historical cohort (n = 622; mean follow-up, 9.2 years) and then matched to different DMT groups. Patients were matched on gender, baseline age, annualized-relapse rate, Expanded Disability Status Scale (EDSS) score, and disease duration. The researchers used weighted conditional proportional hazards models adjusted for EDSS frequency with pairwise censoring to compare the proportions of patients in each group who were free from conversion to secondary progressive MS.

Because lower-efficacy drug groups may have been biased towards participants with milder disease through excluding patients with multiple DMTs (such as treatment escalators), the investigators limited the injectables group to patients followed up before higher-efficacy drugs became available in 2006.

All DMTs reduced the hazard of conversion to secondary progressive MS, compared with different groups of matched untreated patients, in a series of pairwise analyses. For injectables, the hazard ratio (HR) of conversion to secondary progressive MS was 0.31 (median censored on-treatment follow-up, 7.9 years). For fingolimod, the HR was 0.23 (follow-up, 4.6 years). Natalizumab was associated with an HR of 0.50 (follow-up, 4.9 years). Alemtuzumab had an HR of 0.60 (follow-up, 7.2 years).

When the investigators matched patients between the treated cohorts, they found no significant difference in rate of conversion to secondary progressive MS between alemtuzumab and natalizumab. Alemtuzumab and natalizumab were therefore combined in a category of high-efficacy therapies (n = 118) and matched and compared with the injectables group (n = 236). High-efficacy therapies conferred greater protection against conversion to secondary progressive MS than injectables did (HR, 0.65; follow-up, 5.7 years).