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Induction versus escalation in multiple sclerosis: a 10-year real-world study
L. Prosperini1, C.R. Mancinelli2, C.M. Solaro3, V. Nociti4, S. Haggiag1, C. Cordioli2, L. De Giglio5, N. De Rossi2, S. Galgani1, F. Gurreri5, S. Rasia2, S. Ruggieri5, C. Tortorella1, R. Capra2, M. Mirabella4, C. Gasperini1 1S. Camillo-Forlanini Hospital, Rome, 2Multiple Sclerosis Centre, ASST Spedali Civili di Brescia, P.O. Montichiari, Brescia, 3Rehabilitation Unit 'Mons. L. Novarese' Hospital, Loc.Trompone, Moncrivello (VC), 4Fondazione Policlinico Universitario ‘A. Gemelli’, IRCCS, Università Cattolica del Sacro Cuore, 5Sapienza University, Rome, Italy
Background: Escalation and induction are the main treatment strategy adopted in multiple sclerosis (MS). Escalation refers to starting in newly diagnosed patients with less potent, but relatively safe, agents and eventually moving on to more potent drugs in case of disease activity. Induction refers to starting early on high-efficacy immunosuppressant agents, followed by maintenance with immunomodulation. To date, induction is rarely used only in aggressive MS, and long-term real-world data are not available.
Objective: To directly compare escalation and induction strategies on the risk of reaching the disability milestone of Expanded Disability Status Scale (EDSS) ≥6.0 over a 10-year follow-up.
Methods: We collected data of patients with relapsing-remitting MS who started interferon beta (escalation) and mitoxantrone or cyclophosphamide (induction) as initial treatment. The main inclusion criteria were: age < 55 years; < 5 years since MS onset; EDSS ≤4.0; ≥1 relapse in previous year. We performed a 1:1 ratio propensity score (PS)-based nearest-neighbor matching (without replacement) to select patients with homogeneous baseline characteristics. Comparisons were then conducted using a Cox model stratified by matched pairs, with time to EDSS ≥6.0 as main outcome.
Results: Overall, 738 and 74 eligible patients were started with escalation and induction, respectively. Serious adverse events occurred more frequently in induction (n=8, 10.8%) than in escalation (n=12, 1.6%) group (p< 0.001). At follow-up, 108 (14.6%) and 20 (27.0%) patients reached the outcome in escalation and induction group, respectively (p=0.005). However, there was a significant between-group imbalance in baseline characteristics as for older age, higher EDSS and more pre-treatment relapses in the induction group (p< 0.05). This imbalance did not survive after the PS-matching procedure retaining 148 patients (74 per group). In the re-matched samples, proportions of patients reaching the outcome was lower in induction (n=20, 27.0%) than escalation group (n=28, 37.8%; HR=0.46, p=0.014). We found similar results even after matching in a 1:2 ratio (HR=0.59, p=0.042).
Discussion: In patients with bad prognostic factors, initial treatment with an induction approach was more effective than escalation in preventing the risk of disability milestone, but at the price of a worse safety profile. Further efforts are now warranted to clarify if the newer induction agents could provide a better risk:benefit ratio.
L. Prosperini1, C.R. Mancinelli2, C.M. Solaro3, V. Nociti4, S. Haggiag1, C. Cordioli2, L. De Giglio5, N. De Rossi2, S. Galgani1, F. Gurreri5, S. Rasia2, S. Ruggieri5, C. Tortorella1, R. Capra2, M. Mirabella4, C. Gasperini1 1S. Camillo-Forlanini Hospital, Rome, 2Multiple Sclerosis Centre, ASST Spedali Civili di Brescia, P.O. Montichiari, Brescia, 3Rehabilitation Unit 'Mons. L. Novarese' Hospital, Loc.Trompone, Moncrivello (VC), 4Fondazione Policlinico Universitario ‘A. Gemelli’, IRCCS, Università Cattolica del Sacro Cuore, 5Sapienza University, Rome, Italy
Background: Escalation and induction are the main treatment strategy adopted in multiple sclerosis (MS). Escalation refers to starting in newly diagnosed patients with less potent, but relatively safe, agents and eventually moving on to more potent drugs in case of disease activity. Induction refers to starting early on high-efficacy immunosuppressant agents, followed by maintenance with immunomodulation. To date, induction is rarely used only in aggressive MS, and long-term real-world data are not available.
Objective: To directly compare escalation and induction strategies on the risk of reaching the disability milestone of Expanded Disability Status Scale (EDSS) ≥6.0 over a 10-year follow-up.
Methods: We collected data of patients with relapsing-remitting MS who started interferon beta (escalation) and mitoxantrone or cyclophosphamide (induction) as initial treatment. The main inclusion criteria were: age < 55 years; < 5 years since MS onset; EDSS ≤4.0; ≥1 relapse in previous year. We performed a 1:1 ratio propensity score (PS)-based nearest-neighbor matching (without replacement) to select patients with homogeneous baseline characteristics. Comparisons were then conducted using a Cox model stratified by matched pairs, with time to EDSS ≥6.0 as main outcome.
Results: Overall, 738 and 74 eligible patients were started with escalation and induction, respectively. Serious adverse events occurred more frequently in induction (n=8, 10.8%) than in escalation (n=12, 1.6%) group (p< 0.001). At follow-up, 108 (14.6%) and 20 (27.0%) patients reached the outcome in escalation and induction group, respectively (p=0.005). However, there was a significant between-group imbalance in baseline characteristics as for older age, higher EDSS and more pre-treatment relapses in the induction group (p< 0.05). This imbalance did not survive after the PS-matching procedure retaining 148 patients (74 per group). In the re-matched samples, proportions of patients reaching the outcome was lower in induction (n=20, 27.0%) than escalation group (n=28, 37.8%; HR=0.46, p=0.014). We found similar results even after matching in a 1:2 ratio (HR=0.59, p=0.042).
Discussion: In patients with bad prognostic factors, initial treatment with an induction approach was more effective than escalation in preventing the risk of disability milestone, but at the price of a worse safety profile. Further efforts are now warranted to clarify if the newer induction agents could provide a better risk:benefit ratio.