Two studies in one: A propensity-score-matched comparison of fingolimod versus interferons and glatiramer acetate using real-world data from the independent German studies, PANGAEA and PEARL

Alsop, Jonathan; Medin, Jennie; Cornelissen, Christian; Vormfelde, Stefan Viktor; Ziemssen, Tjalf

doi:10.1371/journal.pone.0173353

Cited by 15 publications

(12 citation statements)

References 46 publications

(65 reference statements)

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“…The overall pattern of AEs or SAEs reported with long-term fingolimod treatment was similar to those reported in the feeder studies, 8–12 and from real-world studies. 13–19 In line with those previous studies, the most commonly reported AEs were headache, lymphopenia, and influenza, all of which showed a clear decreasing trend from year 1 to year 11 in LONGTERMS. In addition to selective drop out in the feeder studies, such a decrease in reported AEs could be due to reduced reporting by the investigators or patients who had adapted to recurring similar AEs.…”

Section: Discussionsupporting

confidence: 89%

“…Fingolimod (FTY720, Gilenya®), a sphingosine 1-phosphate receptor (S1PR) modulator, was the first oral DMT approved for the treatment of relapsing MS (RMS), 5–7 after efficacy and safety were demonstrated in pivotal phase III clinical trials against placebo (FREEDOMS, 8 FREEDOMS II 9 ) and interferon (IFN) beta-1a (TRANSFORMS). 10 First reports from extension studies 11,12 and from the use of fingolimod in real-world settings across different geographical regions 13–19 were consistent with the results of the pivotal studies. However, as for other DMTs, longer-term data on safety and efficacy of fingolimod are needed to optimize treatment strategies for MS disease management in routine clinical practice.…”

Section: Introductionsupporting

confidence: 60%

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Extended treatment with fingolimod for relapsing multiple sclerosis: the 14-year LONGTERMS study results

Cohen

Tenenbaum

Bhatt

et al. 2019

Ther Adv Neurol Disord

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Background: Multiple sclerosis (MS) is a chronic disease that may require decades of ongoing treatment. Therefore, the long-term safety and efficacy of disease-modifying therapies is an important consideration. Methods: The LONGTERMS study evaluated the safety and efficacy of fingolimod in patients with relapsing MS (RMS) with up to 14 years of exposure. This phase IIIb, open-label extension study included patients aged ⩾ 18 years with confirmed RMS diagnosis who completed previous phase II/III/IIIb core/extension studies of fingolimod. Patients received fingolimod 0.5 mg orally once daily; safety and efficacy (clinical and magnetic resonance imaging) were the main outcomes. Results: Of 4086 patients from the core studies who entered LONGTERMS, 3480 (85.2%) completed the study. The median age (range) was 38 (17–65) years and median fingolimod exposure was 944.5 (range 75–4777) days. Overall, 85.5% of patients experienced at least one adverse event (AE); most common AEs (⩾10%) were viral upper respiratory tract infection (17.3%), headache (13.3%), hypertension (11.0%) and lymphopenia (10.7%). Among patients with serious AEs (12.6%), basal cell carcinoma and MS relapse (0.9% each) were most frequently reported. The aggregate annualized relapse rate decreased from 0.22 (in years 0–2) to 0.17 (years 0–10); 45.5% of patients remained relapse free after 10 years. At year 10, 63.2% of patients were free from 6-month confirmed disability worsening. Conclusion: This long-term observational study of patients treated for up to 14 years with fingolimod confirmed its established safety profile with no new safety concerns. Patients with RMS receiving fingolimod had sustained low levels of disease activity and progression. Trial Registration: ClinicalTrials.gov identifier: NCT01201356.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionsupporting

confidence: 60%

Extended treatment with fingolimod for relapsing multiple sclerosis: the 14-year LONGTERMS study results

Cohen

Tenenbaum

Bhatt

et al. 2019

Ther Adv Neurol Disord

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“…Overall, the proportion of participants who were male (44/94, 47%) was higher than that seen in a recent German observational study of patients with MS using interferons or glatiramer acetate (120/429, 28%) [19]. This proportional shift may be due to the digital study design.…”

Section: Discussionmentioning

confidence: 65%

Assessment of Medication Adherence Using a Medical App Among Patients With Multiple Sclerosis Treated With Interferon Beta-1b: Pilot Digital Observational Study (PROmyBETAapp)

et al. 2019

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BackgroundAccurate measurement of medication adherence using classical observational studies typically depends on patient self-reporting and is often costly and slow. In contrast, digital observational studies that collect data directly from the patient may pose minimal burden to patients while facilitating accurate, timely, and cost-efficient collection of real-world data. In Germany, ~80% of patients with multiple sclerosis (MS) treated with interferon beta 1b (Betaferon) use an electronic autoinjector (BETACONNECT), which automatically records every injection. Patients may also choose to use a medical app (myBETAapp) to document injection data and their well-being (using a “wellness tracker” feature).ObjectiveThe goal of this pilot study was to establish a digital study process that allows the collection of medication usage data and to assess medication usage among patients with MS treated with interferon beta-1b who use myBETAapp.MethodsThe PROmyBETAapp digital observational study was a mixed prospective and retrospective, noninterventional, cohort study conducted among users of myBETAapp in Germany (as of December 2017: registered accounts N=1334; actively used accounts N=522). Between September and December 2017, users received two invitations on their app asking them to participate. Interested patients were provided detailed information and completed an electronic consent process. Data from consenting patients’ devices were collected retrospectively starting from the first day of usage if historical data were available in the database and collected prospectively following consent attainment. In total, 6 months of data on medication usage behavior were collected along with 3 months of wellness tracker data. Descriptive statistics were used to analyze persistence, compliance, and adherence to therapy.ResultsOf the 1334 registered accounts, 96 patients (7.2%) provided informed consent to participate in the study. Of these, one patient withdrew consent later. For another patient, injection data could not be recorded during the study period. Follow-up of the remaining 94 patients ended in May 2018. The mean age of participants was 46.6 years, and 50 (53%) were female. Over the 6-month study period, persistence with myBETAapp usage was 96% (90/94), mean compliance was 94% of injections completed, and adherence (persistence and ≥80% compliance) was 89% (84/94). There was no apparent difference between male and female participants and no trend across age groups. The wellness tracker was used by 21% of participants (20/94), with a mean of 3.1 entries per user.ConclusionsThis study provides important information on medication usage among patients with MS treated with interferon beta-1b and on consenting behavior of patients in digital studies. In future studies, this approach may allow patients’ feedback to be rapidly implemented in existing digital solutions.Trial RegistrationClinicalTrials.gov NCT03134573; https://clinicaltrials.gov/ct2/show/NCT03134573

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“…15,16 Data on drug-use patterns of DMDs in clinical practice and the incidence of serious adverse events from Germany is scarce. Available evidence is mostly restricted to studies of individual drugs [17][18][19][20][21][22][23] or is almost outdated and does not cover newer drugs, such as natalizumab or fingolimod. 24 Therefore, the objective of this study was to describe the clinical characteristics and drug-use patterns of MS patients using DMDs and to estimate the incidence of severe adverse events in DMD users.…”

Section: Introductionmentioning

confidence: 99%

<p>Drug-use patterns and severe adverse events with disease-modifying drugs in patients with multiple sclerosis: a cohort study based on German claims data</p>

Simbrich¹,

Thibaut²,

Khil³

et al. 2019

NDT

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Purpose: To describe drug-use patterns in patients with multiple sclerosis (MS) using disease-modifying drugs (DMDs) and to estimate the incidence of severe adverse events (SAEs) of treatment. Methods: We conducted a cohort study within the German Pharmacoepidemiological Research Database between January 1, 2006 and December 31, 2013. MS patients on DMDs were described in terms of clinical characteristics and drug-use patterns. Next, we assessed the incidence of AEs in new users of fingolimod, natalizumab, glatiramer acetate, and IFNβ 1a. Results: Among approximately 11 million insured members of German Statutory Health Insurance, the DMD-user cohort comprised 15,377 patients with MS, with a mean age of 39.6 years and 68% females. Nearly half of all DMD users had a diagnosis of depression, with prevalence ranging from 40.1% for IFNβ 1a to 62.3% for immunoglobulins. The overall rate of MS relapses per patient and year was 0.34 (95% CI 0.33-0.34). During an average follow-up of 1,650 days, the majority (42.4%) of MS patients were adherent to DMD treatment ("continuous single users"), followed by patients interrupting treatment (39.5%, "interrupters"). Switch of DMD treatment (11.9%) was less frequent, and only 5.6% discontinued treatment. Treatment discontinuation was most common in users of natalizumab (7.5%) and IFNβ 1b (7.0%). The most frequent SAE was hospitalization for depression, followed by any infectious disease and any malignancy. The incidence rate of all adverse events did not significantly differ across different DMDs. Conclusion: Treatment discontinuation with DMDs and treatment switch were rare. Causes of rather frequent DMD-treatment interruption have to be evaluated in further studies based on primary data collection. Active safety monitoring of new DMDs based on claims data requires large data sets to detect rare AEs and availability of up-to-date data.

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Two studies in one: A propensity-score-matched comparison of fingolimod versus interferons and glatiramer acetate using real-world data from the independent German studies, PANGAEA and PEARL

Cited by 15 publications

References 46 publications

Extended treatment with fingolimod for relapsing multiple sclerosis: the 14-year LONGTERMS study results

Extended treatment with fingolimod for relapsing multiple sclerosis: the 14-year LONGTERMS study results

Assessment of Medication Adherence Using a Medical App Among Patients With Multiple Sclerosis Treated With Interferon Beta-1b: Pilot Digital Observational Study (PROmyBETAapp)

<p>Drug-use patterns and severe adverse events with disease-modifying drugs in patients with multiple sclerosis: a cohort study based on German claims data</p>

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