A real world experience with fingolimod in active RRMS patients naïve to second-line agents: a 2 years, intention-to-treat, observational, single center study

Abstract

Background: Fingolimod is approved by EMA as a second-line treatment for relapsing-remitting multiple sclerosis (RRMS). Experience with fingolimod in real life is still limited. Aim of our study was to report data on fingolimod effectiveness in a real life cohort of Italian active RRMS patients, naïve to second-line agents, followed for 2 years. Fingolimod was a part of the patients' regular treatment and is produced by Novartis. Methods: We included all consecutive RRMS patients starting fingolimod at our center according to EMA criteria before January 1st 2013. Exclusion criteria were a previous treatment with natalizumab or an immunosuppressant therapy in the previous 12 months. All patients were clinically evaluated quarterly, and performed brain MRI yearly. Definition of "no evidence of disease activity" (NEDA-3): no relapses, no brain MRI activity and no 6-months confirmed worsening in EDSS score. Results: We included 38 RRMS patients, 35 switched from first-line injectable therapies. Six patients were also previously treated with immunosuppressants (5 mitoxantrone, 1 cyclophosphamide). At 24 th month 34 patients continued fingolimod treatment. Main adverse events were infections (18 %), liver-enzymes elevation (8 %), and leukopenia (8 %). After 12 and 24 months 79 and 63 % of patients were relapses-free. Fingolimod significantly reduced ARR compared to the previous year (0.3 ± 0.6 vs 1.2 ± 0.5; p < 0.001). After 12 and 24 months 63 and 37 % of patients had NEDA-3. Previous use of immunosuppressants and an ARR ≥1 in the 2 years predicted disease activity. Conclusion: Fingolimod significantly reduce disease activity in active RRMS patients, with no severe/ unexpected safety issues. Patients previously treated with immunosuppressants and with a higher ARR at baseline may respond less to fingolimod treatment.

Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry

“…Our findings confirmed fingolimod effectiveness in reducing relapse activity seen in pivotal trials [ 7 , 9 ]. The ARR after 1 year of treatment (0.32) was similar to those reported in other RWE studies (0.28 [ 24 ], 0.31 [ 26 ], 0.32 [ 27 , 28 ]) and between the range of other lower (0.23 [ 14 ]) and higher (0.42 [ 30 ]) ARR findings. Notably, the ARR continued to decrease with each year of fingolimod treatment.…”

“…The novelty and strength of the present study lies in the fact that, to our knowledge, it is one of the first studies reporting data from patients treated with fingolimod stratified according to prior treatment with a follow-up of 4 years. This is a longer follow-up than in previous prospective studies, including both observational studies [ 11 , 26 , 27 ] and clinical trials [ 7 , 9 ], or the observational period in retrospective studies which has usually been 1 or 2 years [ 14 , 24 , 25 , 28 ], with a maximum follow-up of 3 years [ 11 ].…”

“…Compared to the FREEDOMS and TRANSFORMS clinical trials [ 7 , 9 ], patients in our study were older (39.1 years old vs 36.6 in FREEDOMS and 36.7 in TRANSFORMS), had higher EDSS scores (3.03 vs 2.3 in FREEDOMS and 2.24 in TRANSFORMS), and a higher proportion of patients had received at least on prior DMT (91.1% vs 42.6% in FREEDOMS and 55.2% in TRANSFORMS). However, when these baseline characteristics are compared with other real-world evidence (RWE) studies, the profile in terms of age, EDSS, or prior DMT use [ 11 , 14 , 24 – 27 ] is similar, although older patients and higher EDSS scores were also reported [ 28 ]. These differences in patient profile between the pivotal trials and RWE studies reinforce the importance of conducting studies in more realistic conditions to complement clinical trial data.…”

The real-world effectiveness and safety of fingolimod in relapsing-remitting multiple sclerosis patients: An observational study

“…For example, in Europe only six observational studies have been performed, five studies in Italy and one in Portugal [10,11,15–18], all of which had a limited patient numbers and/or short follow-up periods [10,11,15–18]. …”

“…As fingolimod is a relatively new MS treatment, most of the observational studies that have been published to date, have included only a limited number of patients and/or followed the cohort of patients for a short period of time [ 8 – 18 ]. For example, in Europe only six observational studies have been performed, five studies in Italy and one in Portugal [ 10 , 11 , 15 – 18 ], all of which had a limited patient numbers and/or short follow-up periods [ 10 , 11 , 15 – 18 ].…”