Real-world evidence and patient preference for subcutaneous versus intravenous natalizumab in the treatment of relapsing-remitting multiple sclerosis - initial results from the observational SISTER study.

Background: The consideration of patient preference for a certain drug route of administration (RoA) plays an important role in promoting patient adherence in chronic diseases. Natalizumab is an established treatment for relapsing-remitting multiple sclerosis (RRMS) and can be administered as intravenous (IV) infusion or subcutaneous (SC) injection developed to enable a shorter and easier administration versus IV RoA. Study objectives: Primary objective is to compare patients' preference for RoA and satisfaction with SC versus IV natalizumab at baseline and subsequent visits up to 12 months. Secondary objectives include drug utilization, clinical outcomes, safety, and treatment satisfaction in a usual care setting. Design and methods: SISTER (Subcutaneous: Non-Interventional Study for Tysabri Patient Preference - Experience from Real World) is an ongoing, prospective, observational study where natalizumab is utilized according to local label. RRMS patients are included in three natalizumab cohorts: Patients switching from current IV to SC administration (switcher) and patients newly starting natalizumab on either SC or IV route (starter SC/IV). This interim analysis includes 262 patients (184 switchers, 39 SC starters, and 39 IV starters), median observation period was 9 months. Results: 80.8% IV starters and 93.9% SC starters reported at baseline that they prefer the assigned RoA. Although initial satisfaction with chosen RoA was maintained over time from baseline through Month 12 in all three cohorts, the wish for change of the current RoA after 6 and 12 months was more frequently expressed among IV starters than in either SC cohort. Consistently, six patients (23.1%) starting with IV changed their RoA from IV to SC route.Mean global treatment satisfaction according to TSQM-II score at baseline remained high in the switcher group and increased through Month 12 in both IV and SC starter cohorts. Conclusion: Based on current data, there is a trend toward patients' preference for the natalizumab SC route over the IV route, which provides valuable insights into patients' preference for natalizumab RoA in routine care and complements available data from clinical studies with real-world data on SC natalizumab. Trial registration: This observational (non-interventional) study was registered in the local German PEI register for non-interventional studies (NIS-No. 611) and in the international CTgov register (NCT05304520).

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.

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.

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.

Efficacy and safety of fumaric acid esters in combination with phototherapy in patients with moderate-to-severe plaque psoriasis (FAST).

BACKGROUND: While treatment of patients with moderate-to-severe psoriasis using a combination of fumaric acid esters (FAE, Fumaderm® ) and phototherapy (UV) is common practice, there have been hardly any studies investigating this regimen. Available information is limited to data from a small pilot study. The objective of the present study was to evaluate FAE/UV combination therapy in a larger patient cohort with moderate-to-severe psoriasis. PATIENTS AND METHODS: In this prospective noninterventional multicenter study, data from patients treated with FAE/UV combination therapy was assessed with regard to efficacy (PGA' PASI, DLQI, EQ-5D), safety, and dosage over a twelve-month period. The findings were subsequently compared to data from a previous retrospective study on FAE monotherapy. RESULTS: Data from 363 patients was included in the analysis. Efficacy measures improved substantially on combination therapy. Compared to FAE monotherapy, FAE/UV therapy led to a faster clinical response, however, there was no difference in efficacy after 12 months. Neither the duration nor the type of phototherapy had an impact on efficacy. In general, combination therapy was well tolerated. Seven percent of patients experienced adverse events. CONCLUSIONS: FAE/UV combination therapy is effective and well tolerated in patients with moderate-to-severe psoriasis. Such treatment may induce a faster therapeutic response, and appears to be useful, particularly in the first three months of FAE therapy.

Wirksamkeit und Sicherheit von Fumarsäureestern in Kombination mit Phototherapie bei Patienten mit moderater bis schwerer Plaque-Psoriasis (FAST).

HINTERGRUND: Die Behandlung von Psoriasis-Patienten mit einer Kombination aus Fumarsäureestern (FSE, Fumaderm® ) und Phototherapie (UV) ist verbreitet, wurde aber im Rahmen von Studien wenig untersucht. Bisher liegen lediglich Daten aus einer kleinen Pilotstudie vor. Intention dieser Studie war, eine FSE/UV-Kombinationsbehandlung an einem größeren Patientenkollektiv mit mittelschwerer bis schwerer Psoriasis zu untersuchen. PATIENTEN UND METHODIK: In dieser prospektiven, multizentrischen, nichtinterventionellen Studie wurden Daten von Patienten mit FSE/UV-Kombinationstherapie hinsichtlich der Wirksamkeit (PGA' PASI, DLQI, EQ-5D), Sicherheit und Dosierung über einen Zeitraum von zwölf Monaten erfasst und mit Daten einer retrospektiven Studie mit FSE-Monotherapie verglichen. ERGEBNISSE: Es wurden Daten von 363 Patienten ausgewertet. Unter der Kombinationstherapie verbesserten sich alle Wirksamkeitsparameter deutlich. Im Vergleich zur Monotherapie mit FSE konnte durch die Kombination mit UV ein schnellerer Wirkeintritt erzielt werden, wobei nach zwölf Monaten kein Unterschied in der Wirksamkeit bestand. Die Dauer und Art der Phototherapie zeigte keinen Einfluss auf die Wirksamkeitsparameter. Allgemein wurde die Kombinationstherapie gut vertragen. Unerwünschte Ereignisse wurden bei 7 % der Patienten berichtet. SCHLUSSFOLGERUNGEN: Die FSE/UV Kombinationstherapie zeigt eine gute Wirksamkeit und Verträglichkeit und kann zu einem schnelleren Wirkeintritt führen. Eine Kombinationstherapie erscheint vor allem in den ersten drei Monaten der FSE Behandlung sinnvoll.

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.