Confirmed Progression independent of Relapse Activity in Multiple Sclerosis Patients under long-term Natalizumab Treatment.

Objective: To evaluate confirmed progression independent of relapse activity (cPIRA) as an indicator for secondary progressive multiple sclerosis (SPMS) during long-term natalizumab treatment in relapsing-remitting multiple sclerosis (RRMS) patients. Background: While early natalizumab treatment may delay SPMS conversion, real-world data on the long-term effect are rare. Design/Methods: We performed a retrospective chart review study of RRMS patients on long-term (≥24 months) natalizumab therapy at the University hospitals of Dusseldorf and Munich. cPIRA was defined as ≥12 week confirmed disability progression on a roving Expanded Disability Status Scale (EDSS) reference score by 1 point in patients with EDSS ≤3 or 0.5 in patients with EDSS ≥3.5 in the absence of a relapse. Results: We identified 194 patients on long-term natalizumab therapy. Of these patients, 44 developed cPIRA under natalizumab (22.7%), 140 patients remained relapsing-remitting (72.2%) and 10 patients developed cPIRA outside natalizumab therapy (5.1%). Kaplan Meier curves with cox proportional hazard models were used to analyze cPIRA development depending on both disease and natalizumab treatment duration. cPIRA occurred earlier in the disease course in patients with an earlier natalizumab therapy onset (≤8.6 versus >8.6 years, p 3.5 at natalizumab onset neither in disease (p=0.075) nor in therapy duration (p=0.565). Furthermore, patients with >2 disease-modifying therapies (DMT) before natalizumab developed cPIRA significantly earlier in the disease course than patients with ≤2 DMTs prior to natalizumab (p=0.005), but the duration of natalizumab therapy before cPIRA did not differ (p=0.876). Conclusions: More than 20% of patients on long-term natalizumab treatment developed cPIRA independent of the EDSS at natalizumab onset. The significant difference regarding the natalizumab onset analyses reflects that patients with a more severe disease course are more likely to receive natalizumab earlier. Disclosure: Dr. Graf has nothing to disclose. Dr. Leussink has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis. Dr. Leussink holds stock and/or stock options in Biogen. Dr. Leussink has received research support from Biogen, Novartis. Dr. Soncin has nothing to disclose. Dr. Lepka has nothing to disclose. Dr. Meinl has nothing to disclose. Dr. Kuempfel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer Healthcare, Teva Pharma, Merck, Novartis Pharma, Sanofi-Aventis/Genzyme, CLB Behring, Roche Pharma, and Biogen. Dr. Kuempfel has received research support from Bayer-Schering AG, Novartis, and Chugai Pharma. Dr. Hartung has received personal compensation from Bayer Healthcare, Biogen Idec, CSL Behring, GeNeuro, Genzyme, MedImmune, Merck Serono, Novartis, Opexa, Receptos, Roche, Sanofi, Teva, and Viela Bio.Dr. Havla has received research support from Merck, Novartis, Roche, Santhera, Biogen, Alexion, and Sanofi Genzyme.Dr. Aktas has received personal compensation from Almirall, Bayer HealthCare, Biogen, Genzyme, MedImmune, Merck Serono, Novartis, Roche, Teva, Viela Bio. Dr. Aktas has received research support from Bayer HealthCare, Biogen, Genzyme, Novartis, Teva and Viela BioDr. Albrecht has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Allergan, Merz Pharmaceuticals, Novartis, Roche, Teva, Ipsen, Bayer and Merck.