Adherence and cost in multiple sclerosis patients treated with IM IFN beta-1a: impact of the CARE patient management program.

BACKGROUND: Disease modifying treatments (DMT) for MS such as interferon beta (IFNß) have been shown to reduce the risk for disease progression. Therefore adherence to treatment is essential for treatment outcome.Here we want to evaluate if participation in a patient management program (PMP) improves adherence to DMT as well as health and cost outcomes associated with MS. METHODS: In this open-label multicentre prospective observational study, German MS patients treated with once weekly intramuscular (IM) IFNß-1a (Avonex), were offered participation in a PMP and followed for up to 12 months. The PMP included injection trainings, support and quarterly visits for up to 12 months after initiation of therapy. Utilisation of health care services was evaluated. The primary endpoint was to evaluate the direct and indirect cost associated with MS from payer, patient and societal perspective, in patients who participate in the PMP. Secondary endpoint was the clinical outcome in patients who participate in the PMP (differentiated in adherent versus non-adherent patients). RESULTS: In total 731 patients (mean age: 38.2, 73.7% female) were enrolled, 640 (88%) were observed for twelve months. After six months 34% of patients had participated in the PMP continuously and 21% temporarily; 39% had not participated. After twelve months, the proportions of participants were: 37% continuously and 19% temporarily; 40% had not participated. After 6 months, mean reduction in cost per patient in the participants group (€ 2151) was almost twice as high as the cost reduction amongst non-participants (€ 1131). After twelve months, the annual relapse rate was reduced by 58% compared to baseline in both the participant and non-participant groups. CONCLUSIONS: In a real-world-setting, participation in a patient management program was associated with improved medication adherence and lower total MS-related direct and indirect cost over time.

Interferon Beta-1a (AVONEX®) as a Treatment Option for Untreated Patients with Multiple Sclerosis (AXIOM): A Prospective, Observational Study.

The efficacy and safety of first-line disease-modifying therapies (DMT) for relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in pivotal, randomized trials, but these studies do not reflect the routine care setting where treatment gaps or switches are common. The Avonex as Treatment Option for Untreated MS Patients (AXIOM) trial assessed the efficacy of newly-initiated intramuscular interferon beta-1a (IM IFNb-1a) after a treatment-free interval, with particular consideration of the previous course of disease and therapy. The AXIOM trial was an open, 12-month, observational, non-interventional study with a retrospective and a prospective part conducted in Germany. RRMS patients with a treatment-free interval of at least three months were included and treated with IFNb-1a for up to 12 months. Relapse rate, disability progression, injection-related parameters and quality of life observed during the prospective part were compared with retrospectively-collected data. Two hundred and thirty five RRMS patients participated in AXIOM. The mean relapse rate decreased from 1.1 in the three months before baseline to 0.2 per quarter during the twelve-month observational period; the Multiple Sclerosis Functional Composite score improved during twelve months of IM IFNb-1a treatment, while the Expanded Disability Status Scale score did not change over the course of this study. Compared to previous DMTs (IM IFNb-1a, subcutaneous IFNb-1a (SC IFNb-1a), SC IFNb-1b, glatiramer acetate), the patients experienced less injection site reactions and flu-like symptoms, with a stated improved quality of life. IM IFNb-1a was effective and well accepted in RRMS patients with no or discontinued previous therapy. These results from the routine care setting may inform optimization of DMT treatment in RRMS, but need confirmation in further studies.

Impact of interferon beta exposure on birth outcome and child development - Results from the post-authorisation safety study PRIMA.

BACKGROUND: Interferon beta therapies are well-established disease-modifying treatments for patients with relapsing multiple sclerosis (MS). Based on clinical evidence from two large cohort studies, both, the EMA and FDA updated the labels of the interferon beta class in terms of pregnancy and breastfeeding in 2019 and 2020, respectively. To complement pregnancy label updates with patient-reported real-world data, this study examined German pregnancy and outcome reports including available data on child development from women with MS treated with peginterferon beta-1a or intramuscular (IM) interferon beta-1a. METHODS: The post-authorisation safety study PRIMA included adult women diagnosed with relapsing-remitting MS or clinically isolated syndrome, who were treated with peginterferon beta-1a or IM interferon beta-1a before or during pregnancy and registered in the marketing authorisation holder's MS Service center patient support program. In the prospective part of the study, conducted from April to October 2021, data on developmental milestones of the newborns were collected via telephone interview from mothers reporting live births. RESULTS: In total, 426 women were enrolled, reporting 542 pregnancies that resulted in 466 live births. A total of 162 women completed the questionnaire for 192 live births (53.1% male). Newborns had Apgar scores indicative of healthy infants. Weight, length and head circumference at birth and physical growth curves up to 48 months lay within the expected range of the German general population. Most newborn screenings and examinations during check-ups were inconspicuous over the study period of 48 months. Out of 158 breastfed infants, 112 (70.9%) were breastfed exclusively until month 5. CONCLUSION: Study results confirmed former reports indicating that exposure to interferon beta therapies during pregnancy or lactation had no adverse effects on intrauterine growth and child development over the study period, which covered the first 4 years of life. These real-world data obtained within the scope of a patient support program for peginterferon beta-1a or IM interferon beta-1a corroborate German and Scandinavian registry data and support the label update of all interferon beta therapies. REGISTRATION: NCT04655222, EUPAS38347.

Pregnancy outcomes in female multiple sclerosis patients exposed to intramuscular interferon beta-1a or peginterferon beta-1a reported in a German Patient Support Programme - results from the non-interventional post-authorization safety study PRIMA.

Background: Based on data from two large cohort studies, a label update became applicable for the class of interferon beta therapies in 9/2019, allowing interferons during pregnancy and breastfeeding. Objective: To assess pregnancy outcomes of women with multiple sclerosis (MS) exposed to peginterferon beta-1a or intramuscular interferon beta-1a therapy (IFN). Design: Non-interventional post-authorization safety study. Methods: PRIMA was conducted from April to October 2021 in Germany. Retrospective pregnancy data were retrieved from adult female patients diagnosed with relapsing-remitting MS or clinically isolated syndrome, exposed to IFN before or during pregnancy and registered in the patient support programme (PSP) of the marketing authorization holder's MS Service Centre. The primary endpoint was the outcome of pregnancy. Prospective postpartum data were collected from mothers reporting live births. Results: In total, 426 women reporting 542 pregnancies between December 2001 and July 2020 (14 pregnancies after the label update) were enrolled. Among patients with confirmed exposure during pregnancy (N = 362), 306 pregnancies (84.5%) resulted in live births (77.6% without defects, 1.9% with defects and 4.4% preterm). Spontaneous abortion, elective termination and stillbirth were reported in 10.9%, 2.8% and 0.2% of the cases, respectively. Higher rates of spontaneous abortions were reported in women with continuous IFN use. A total of 162 women completed the questionnaire for 192 live births within the prospective study part. Mothers restarted IFN therapy or switched to another disease-modifying therapy postpartum in 51.0% and 14.1% of cases, respectively. 158/192 infants (82.3%) were breastfed [34/158 (21.5%)] during IFN therapy. Postpartum relapse activity was low (mothers of 87.3% of breastfed infants remained relapse-free during lactation). Conclusion: Overall, the prevalence of spontaneous abortions and congenital anomalies of females exposed to IFN exposure before or during pregnancy was within the range reported for the general population. Most mothers paused IFN during pregnancy and breastfeeding. Relapse activity during pregnancy and lactation was observed to be low. These real-world data from a PSP corroborate European and Scandinavian registry data. Trial registration: NCT04655222, EUPAS38347.

Subcutaneous Interferon Beta Therapy in Multiple Sclerosis Patients - Characterization of Injection Site Reactions and Flu-Like Symptoms in a Daily Practice Setting - Results from the Non-Interventional Study PERFECT.

PURPOSE: The purpose of this study was to assess the prevalence of injection site reactions (ISR) and flu-like symptoms (FLS) during treatment with subcutaneous (SC) interferon (IFN) beta therapies and to document measures to mitigate and prevent ISR and FLS. PATIENTS AND METHODS: The cross-sectional post-authorization safety study PERFECT was conducted from 11/2017 to 7/2019 in neurology practices in Germany. Adult patients with relapsing-remitting multiple sclerosis (MS) receiving SC IFN beta for ≥3 months were eligible. The primary endpoints were patient-reported prevalence of ISR and FLS. Additional endpoints reported by patients, MS nurses, and neurologists included type, frequency, duration, time of occurrence, and management of ISR and FLS. RESULTS: In total, 603 patients (median age 45 years [range 36-53], 74% female) were included in the analysis. Time since MS diagnosis was >5 years in most patients. The majority had received none (64%) or 1 (22%) prior therapy. Current MS therapy in 36%, 32%, and 30% of patients was IFN beta-1b, IFN beta-1a, and peginterferon beta-1a, respectively. ISR and FLS under current therapy were reported by 84% and 68% of patients, respectively. ISR developed within 5 days after injection (84%) and lasted for 2-14 days (53%) in most patients. The most frequent patient-reported symptom was erythema (39%). ISR resolved or abated with systemic treatments or topical ointments. Most frequent preventive measures included alternating injection sites (58%). Occurrence of ISR rarely resulted in treatment interruption (5%). FLS occurred predominantly up to 6 h after injection (40%) and lasted <12 h (26%). The most frequent patient-reported symptoms were fatigue (15%) and aching limbs (15%). Assessments by physicians and MS nurses differed from patient-reported results. CONCLUSION: Although ISR were experienced by the majority of patients, they rarely resulted in treatment interruption. In this real-world setting, ISR and FLS management was in line with published expert recommendations.

Peginterferon beta-1a was associated with high adherence and satisfaction in patients with multiple sclerosis in a German real-world study.

BACKGROUND: Peginterferon beta-1a was developed for treatment of relapsing-remitting multiple sclerosis (RRMS) to provide an interferon with increased exposure to facilitate adherence by reducing frequency of application. This non-interventional observational study investigated the adherence to peginterferon beta-1a in real-world clinical practice settings. METHODS: This prospective study was conducted from 1/2015 to 1/2018 at 77 German MS sites. Adult patients with RRMS (previously treated or treatment-naïve) receiving peginterferon beta-1a (125 µg SC every 2 weeks) were eligible for participation. Data were documented every 3 months over 2 years (nine visits). The primary endpoint was the percentage of patients with overall adherence defined as ⩽10% of injections not administered throughout the 24-month observation period. Secondary endpoints included persistence, patient satisfaction, efficacy (relapse activity, disability progression), and tolerability. Patients were invited to participate in an individualised patient support programme. RESULTS: Out of 250 enrolled patients, 190 (aged 18-74 years, 75.3% female) were included in the efficacy analysis. Of those, 74 patients completed the study; 33.2% were treatment-naïve. The proportion of patients with an overall adherence of >90% was 75.7% (95% CI 67.9-81.6). The annualised relapse rate was 0.17. Compared with previous therapies, the scores for treatment satisfaction and convenience were markedly higher with peginterferon beta-1a. Overall, 87.4% participated in the patient support programme, and 47.8% of patients reported adverse events. CONCLUSIONS: Adherence to the bi-weekly treatment with peginterferon beta-1a was very high. Although adherence could have been positively influenced by the well-accepted patient support programme, the extent could not be unequivocally evaluated. Clinical disease activity remained low. Peginterferon beta-1a was well tolerated, and there were no new relevant safety findings.