MS trial tracks patient-reported benefits of switching from an injectable to fingolimod

Patients with relapsing-remitting multiple sclerosis who switched from an injectable disease-modifying therapy to orally administered fingolimod reported significantly greater treatment satisfaction as well as functional and quality of life outcomes than did those who took the same or a different injectable therapy in a phase IV, open-label, randomized trial.

The results of this trial, called EPOC (Evaluate Patient Outcomes), were similar to those reported for changes in activities of daily living according to the PRIMUS (Patient Reported Indices for Multiple Sclerosis) Activities scale in the double-blind, randomized TRANSFORMS trial that compared fingolimod (Gilenya) to intramuscular interferon beta-1a. However, these measurements did not reach statistical significance in EPOC, possibly because its 6-month duration was not long enough to detect differences, Dr. Edward Fox of Central Texas Neurology Consultants, Round Rock, and his colleagues reported on behalf of the EPOC study investigators.

"Our findings are consistent with those of studies in other diseases, such as thromboembolism prophylaxis, iron chelation, and oncology, which have also found greater levels of patient satisfaction and improved QOL associated with oral versus injectable therapies," the investigators wrote.

For the EPOC trial, investigators from 158 centers in the United States and Canada randomized 1,053 patients with relapsing-remitting MS to either fingolimod 0.5 mg once daily (790 patients) or an injectable disease-modifying therapy (iDMT; 263 patients). The iDMT options included interferon beta-1b subcutaneous 0.25 mg every other day (Betaseron), interferon beta-1a intramuscular 30 mcg once per week (Avonex), interferon beta-1a subcutaneous three times per week (Rebif), or glatiramer acetate subcutaneous 20 mg once daily (Copaxone). The patients had taken an iDMT for at least 6 months and had no washout period before making a switch. They had a mean duration of MS symptoms of 12 years and a mean Expanded Disability Status Scale score of 2.4 (Mult. Scler. Relat. Disord. 2014 July 3 [doi: 10.1016/j.msard.2014.06.005]).

At the time of randomization, most patients were taking glatiramer acetate (33%-35%), followed by intramuscular interferon beta-1a (23%-26%), subcutaneous interferon beta-1a (25% in each), and interferon beta-1b (16%-18%). The patients’ most commonly cited reasons for wishing to switch to a different therapy included mode of administration in 61%-62%, tolerability issues in 13%-14%, and physician-determined lack of efficacy in 12%-16%. Of the 263 patients who stayed on an iDMT, 26 switched to a different drug.

By 6 months, fingolimod-treated patients had significantly higher treatment satisfaction than did those who remained on an iDMT, based on the primary endpoint of difference between the groups on the change in the Global Satisfaction subscale score of the Treatment Satisfaction Questionnaire for Medication. They also reported significant improvements over patients who remained on an iDMT on secondary endpoints that measured changes on the Fatigue Severity Scale, the Beck Depression Inventory II, and the 36-item Short-Form Health Survey’s domains of physical health, bodily pain, vitality, social functioning, role limitation due to emotional problems, and general mental health. The two groups reported no statistically significant differences on changes in perceived activity limitations as measured by the PRIMUS Activities scale.

The physician-rated Clinical Global Impression of Improvement scores significantly favored fingolimod over iDMT (3.2 vs. 3.9, respectively), and although these scores were "in the range of only minimal improvement to no change in both the fingolimod and the iDMT groups, it is worth noting that the effect was measured early in the course of fingolimod treatment in this cohort of patients with long-standing MS," Dr. Fox and his associates wrote.

Adverse events occurred more often among patients who took fingolimod than in those who took an iDMT (79% vs. 62%, respectively), and the most common of these for fingolimod-treated patients were headache and fatigue at 12% each. There was no difference in the incidence of serious adverse events between patients who took fingolimod or an iDMT (4% vs. 2%, respectively), including MS relapse (0.6% vs. 0.8%) and lymphopenia (0.3% vs. 0%). Overall, 41 fingolimod-treated patients discontinued treatment because of an adverse event, compared with 4 iDMT-treated patients.

"Notably, the absence of a washout period between cessation of the iDMT and initiation of fingolimod did not appear to be associated with deleterious additive immune system effects," the investigators wrote.

The study was funded by Novartis, which markets fingolimod. Many authors reported financial relationships with Novartis as well as with the marketers of Betaseron (Bayer HealthCare), Avonex (Biogen Idec), Rebif (EMD Serono and Pfizer), and Copaxone (Teva Neuroscience). Four authors are or were employees of Novartis.

[email protected]

Patients with relapsing-remitting multiple sclerosis who switched from an injectable disease-modifying therapy to orally administered fingolimod reported significantly greater treatment satisfaction as well as functional and quality of life outcomes than did those who took the same or a different injectable therapy in a phase IV, open-label, randomized trial.

The results of this trial, called EPOC (Evaluate Patient Outcomes), were similar to those reported for changes in activities of daily living according to the PRIMUS (Patient Reported Indices for Multiple Sclerosis) Activities scale in the double-blind, randomized TRANSFORMS trial that compared fingolimod (Gilenya) to intramuscular interferon beta-1a. However, these measurements did not reach statistical significance in EPOC, possibly because its 6-month duration was not long enough to detect differences, Dr. Edward Fox of Central Texas Neurology Consultants, Round Rock, and his colleagues reported on behalf of the EPOC study investigators.

"Our findings are consistent with those of studies in other diseases, such as thromboembolism prophylaxis, iron chelation, and oncology, which have also found greater levels of patient satisfaction and improved QOL associated with oral versus injectable therapies," the investigators wrote.

For the EPOC trial, investigators from 158 centers in the United States and Canada randomized 1,053 patients with relapsing-remitting MS to either fingolimod 0.5 mg once daily (790 patients) or an injectable disease-modifying therapy (iDMT; 263 patients). The iDMT options included interferon beta-1b subcutaneous 0.25 mg every other day (Betaseron), interferon beta-1a intramuscular 30 mcg once per week (Avonex), interferon beta-1a subcutaneous three times per week (Rebif), or glatiramer acetate subcutaneous 20 mg once daily (Copaxone). The patients had taken an iDMT for at least 6 months and had no washout period before making a switch. They had a mean duration of MS symptoms of 12 years and a mean Expanded Disability Status Scale score of 2.4 (Mult. Scler. Relat. Disord. 2014 July 3 [doi: 10.1016/j.msard.2014.06.005]).

At the time of randomization, most patients were taking glatiramer acetate (33%-35%), followed by intramuscular interferon beta-1a (23%-26%), subcutaneous interferon beta-1a (25% in each), and interferon beta-1b (16%-18%). The patients’ most commonly cited reasons for wishing to switch to a different therapy included mode of administration in 61%-62%, tolerability issues in 13%-14%, and physician-determined lack of efficacy in 12%-16%. Of the 263 patients who stayed on an iDMT, 26 switched to a different drug.

By 6 months, fingolimod-treated patients had significantly higher treatment satisfaction than did those who remained on an iDMT, based on the primary endpoint of difference between the groups on the change in the Global Satisfaction subscale score of the Treatment Satisfaction Questionnaire for Medication. They also reported significant improvements over patients who remained on an iDMT on secondary endpoints that measured changes on the Fatigue Severity Scale, the Beck Depression Inventory II, and the 36-item Short-Form Health Survey’s domains of physical health, bodily pain, vitality, social functioning, role limitation due to emotional problems, and general mental health. The two groups reported no statistically significant differences on changes in perceived activity limitations as measured by the PRIMUS Activities scale.

The physician-rated Clinical Global Impression of Improvement scores significantly favored fingolimod over iDMT (3.2 vs. 3.9, respectively), and although these scores were "in the range of only minimal improvement to no change in both the fingolimod and the iDMT groups, it is worth noting that the effect was measured early in the course of fingolimod treatment in this cohort of patients with long-standing MS," Dr. Fox and his associates wrote.

Adverse events occurred more often among patients who took fingolimod than in those who took an iDMT (79% vs. 62%, respectively), and the most common of these for fingolimod-treated patients were headache and fatigue at 12% each. There was no difference in the incidence of serious adverse events between patients who took fingolimod or an iDMT (4% vs. 2%, respectively), including MS relapse (0.6% vs. 0.8%) and lymphopenia (0.3% vs. 0%). Overall, 41 fingolimod-treated patients discontinued treatment because of an adverse event, compared with 4 iDMT-treated patients.

"Notably, the absence of a washout period between cessation of the iDMT and initiation of fingolimod did not appear to be associated with deleterious additive immune system effects," the investigators wrote.

The study was funded by Novartis, which markets fingolimod. Many authors reported financial relationships with Novartis as well as with the marketers of Betaseron (Bayer HealthCare), Avonex (Biogen Idec), Rebif (EMD Serono and Pfizer), and Copaxone (Teva Neuroscience). Four authors are or were employees of Novartis.

[email protected]

Patients with relapsing-remitting multiple sclerosis who switched from an injectable disease-modifying therapy to orally administered fingolimod reported significantly greater treatment satisfaction as well as functional and quality of life outcomes than did those who took the same or a different injectable therapy in a phase IV, open-label, randomized trial.

The results of this trial, called EPOC (Evaluate Patient Outcomes), were similar to those reported for changes in activities of daily living according to the PRIMUS (Patient Reported Indices for Multiple Sclerosis) Activities scale in the double-blind, randomized TRANSFORMS trial that compared fingolimod (Gilenya) to intramuscular interferon beta-1a. However, these measurements did not reach statistical significance in EPOC, possibly because its 6-month duration was not long enough to detect differences, Dr. Edward Fox of Central Texas Neurology Consultants, Round Rock, and his colleagues reported on behalf of the EPOC study investigators.

"Our findings are consistent with those of studies in other diseases, such as thromboembolism prophylaxis, iron chelation, and oncology, which have also found greater levels of patient satisfaction and improved QOL associated with oral versus injectable therapies," the investigators wrote.

For the EPOC trial, investigators from 158 centers in the United States and Canada randomized 1,053 patients with relapsing-remitting MS to either fingolimod 0.5 mg once daily (790 patients) or an injectable disease-modifying therapy (iDMT; 263 patients). The iDMT options included interferon beta-1b subcutaneous 0.25 mg every other day (Betaseron), interferon beta-1a intramuscular 30 mcg once per week (Avonex), interferon beta-1a subcutaneous three times per week (Rebif), or glatiramer acetate subcutaneous 20 mg once daily (Copaxone). The patients had taken an iDMT for at least 6 months and had no washout period before making a switch. They had a mean duration of MS symptoms of 12 years and a mean Expanded Disability Status Scale score of 2.4 (Mult. Scler. Relat. Disord. 2014 July 3 [doi: 10.1016/j.msard.2014.06.005]).

At the time of randomization, most patients were taking glatiramer acetate (33%-35%), followed by intramuscular interferon beta-1a (23%-26%), subcutaneous interferon beta-1a (25% in each), and interferon beta-1b (16%-18%). The patients’ most commonly cited reasons for wishing to switch to a different therapy included mode of administration in 61%-62%, tolerability issues in 13%-14%, and physician-determined lack of efficacy in 12%-16%. Of the 263 patients who stayed on an iDMT, 26 switched to a different drug.

By 6 months, fingolimod-treated patients had significantly higher treatment satisfaction than did those who remained on an iDMT, based on the primary endpoint of difference between the groups on the change in the Global Satisfaction subscale score of the Treatment Satisfaction Questionnaire for Medication. They also reported significant improvements over patients who remained on an iDMT on secondary endpoints that measured changes on the Fatigue Severity Scale, the Beck Depression Inventory II, and the 36-item Short-Form Health Survey’s domains of physical health, bodily pain, vitality, social functioning, role limitation due to emotional problems, and general mental health. The two groups reported no statistically significant differences on changes in perceived activity limitations as measured by the PRIMUS Activities scale.

The physician-rated Clinical Global Impression of Improvement scores significantly favored fingolimod over iDMT (3.2 vs. 3.9, respectively), and although these scores were "in the range of only minimal improvement to no change in both the fingolimod and the iDMT groups, it is worth noting that the effect was measured early in the course of fingolimod treatment in this cohort of patients with long-standing MS," Dr. Fox and his associates wrote.

Adverse events occurred more often among patients who took fingolimod than in those who took an iDMT (79% vs. 62%, respectively), and the most common of these for fingolimod-treated patients were headache and fatigue at 12% each. There was no difference in the incidence of serious adverse events between patients who took fingolimod or an iDMT (4% vs. 2%, respectively), including MS relapse (0.6% vs. 0.8%) and lymphopenia (0.3% vs. 0%). Overall, 41 fingolimod-treated patients discontinued treatment because of an adverse event, compared with 4 iDMT-treated patients.

"Notably, the absence of a washout period between cessation of the iDMT and initiation of fingolimod did not appear to be associated with deleterious additive immune system effects," the investigators wrote.

The study was funded by Novartis, which markets fingolimod. Many authors reported financial relationships with Novartis as well as with the marketers of Betaseron (Bayer HealthCare), Avonex (Biogen Idec), Rebif (EMD Serono and Pfizer), and Copaxone (Teva Neuroscience). Four authors are or were employees of Novartis.

[email protected]