Peginterferon Beta-1a Research Articles

Efficacy and safety of peginterferon beta-1a compared to interferon beta-1a in relapsing remitting multiple sclerosis patients: A phase 3, randomized, non-inferiority clinical trial (PEGINTEGRITY)

BackgroundMultiple sclerosis (MS) is a prevalent, disabling, inflammatory, neurodegenerative disease that typically manifests during a highly productive stage of life. Interferon beta-1a was among the first approved disease-modifying therapies for MS and remains among the first-line treatment options. Pegylation of the interferon beta-1a molecule prolongs its half-life while maintaining its efficacy and safety profile. In PEGINTEGRITY study, we aimed to compare peginterferon beta-1a with interferon beta-1a in terms of efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) patients. MethodsThis study was a randomized, active-controlled, parallel-group, multi-center Phase 3 trial conducted in Iran in participants with RRMS. Participants received 125 µg of subcutaneous peginterferon beta-1a every two weeks or 30 µg of intramuscular interferon beta-1a once a week for up to 96 weeks. The primary outcome was the non-inferiority of peginterferon beta-1a to interferon beta-1a in reducing annualized relapse rate (ARR). Other outcomes included the number of patients with 12-week confirmed disability progression, the number of new or newly-enlarging T2 hyperintense lesions, the number of gadolinium-enhancing lesions, the number of new T1 hypointense lesions, the volume of new or newly-enlarging T2 hyperintense lesions, changes in brain volume, immunogenicity, and safety assessments. ResultsA total of 168 patients who met the eligibility criteria were enrolled and assigned to two arms of the study, each consisting of 84 participants. Totally, 41 participants (24 patients in the peginterferon beta-1a group and 17 patients in the interferon beta-1a group) were withdrawn from the study. The withdrawn patients were included in the per-protocol analysis for the period of time they were in the study. In 96 weeks, in the per-protocol population, the ARR was 0.05 in the peginterferon beta-1a group versus 0.11 in the interferon beta-1a group, which does not reflect a statistically significant difference (p=0.09; 95 % CI, 0.18-1.14). Considering the upper limit of the one-sided 95 % CI of the rate ratio of peginterferon beta-1a compared to interferon beta-1a, as well as the non-inferiority margin, it can be concluded that the primary outcome was met. The results were also comparable for other efficacy and safety outcomes. ConclusionThe results demonstrate the non-inferiority of peginterferon beta-1a to interferon beta-1a with similar efficacy in 96-week ARR in RRMS patients. Both arms were also comparable in other efficacy outcomes and safety profiles with no statistically significant differences. These findings support considering peginterferon beta-1a as a safe and efficient option in patients with RRMS.This study was registered on Iranian Registry of Clinical Trials (IRCT201612306135N8) and clinicaltrials.gov (NCT05242133).

Safety and clinical effectiveness of peginterferon beta-1a for relapsing multiple sclerosis in a real-world setting: Final results from the Plegridy Observational Program.

Interferon beta-1a remains an important treatment option for multiple sclerosis, particularly when safety or tolerability concerns may outweigh the benefits of higher-efficacy disease-modifying therapies. The five-year phase 4 Plegridy Observational Program (POP) study (NCT02230969) collected data on real-world safety and effectiveness of Plegridy® (peginterferon beta-1a) treatment in patients with relapsing multiple sclerosis. To explore the real-world safety and effectiveness of peginterferon beta-1a in patients with relapsing multiple sclerosis, including factors influencing treatment discontinuation. Data were collected prospectively from patients ≥ 18 years old with relapsing multiple sclerosis for overall population analysis and for subpopulations including newly/previously diagnosed patients, age, and experience with peginterferon beta-1a. Outcome measures included annualized relapse rates, adverse events, and predictors of time to treatment discontinuation. Mean (SD) treatment duration in the overall population (N = 1172) was 896.0 (733.15) days. Incidence of adverse events was higher in new than experienced users (79.4% vs. 57.0%). New users were more likely than experienced users to discontinue (hazard ratio = 1.60; P < 0.0001). The adjusted annualized relapse rate was 0.09, and at the end of 5 years, 77.1% of patients were relapse-free. Peginterferon beta-1a is an effective therapy for managing relapsing multiple sclerosis. The identification of predictors of discontinuation can help inform strategies to enhance treatment persistence.

Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis.

Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis.

Interferon β-1a ring prophylaxis to reduce household transmission of SARS-CoV-2: a cluster randomised clinical trial

Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNβ-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125μg subcutaneous pegylated IFNβ-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n=831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNβ-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNβ-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction=-0.2%, 95% CI=-8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction=3.87%, 95% CI=-3.6% to 11.3%). Treatment with IFNβ-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Based upon the primary analyses, IFNβ-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Biogen PTY Ltd. Supply of interferon as 'Plegridy (peginterferon beta-1a).' The study was substantially funded by BHP Holdings Pty Ltd.

Darren P. Baker, PhD A Pioneer in the Development of Pegylated Interferon-β for Clinical Use

Darren P. Baker, PhD A Pioneer in the Development of Pegylated Interferon-β for Clinical Use

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.

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. To assess pregnancy outcomes of women with multiple sclerosis (MS) exposed to peginterferon beta-1a or intramuscular interferon beta-1a therapy (IFN). Non-interventional post-authorization safety study. 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. 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). 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. NCT04655222, EUPAS38347.

Multiple sclerosis clinical decision support system based on projection to reference datasets.

Multiple sclerosis (MS) is a multifactorial disease with increasingly complicated management. Our objective is to use on-demand computational power to address the challenges of dynamically managing MS. A phase 3 clinical trial data (NCT00906399) were used to contextualize the medication efficacy of peg-interferon beta-1a vs placebo on patients with relapsing-remitting MS (RRMS). Using a set of reference patients (PORs), selected based on adequate features similar to those of an individual patient, we visualize disease activity by measuring the percentage of relapses, accumulation of new T2 lesions on MRI, and worsening EDSS during the clinical trial. We developed MS Vista, a functional prototype of clinical decision support system (CDSS), with a user-centered design and distributed infrastructure. MS Vista shows the medication efficacy of peginterferon beta-1a versus placebo for each individual patient with RRMS. In addition, MS Vista initiated the integration of a longitudinal magnetic resonance imaging (MRI) viewer and interactive dual physician-patient data display to facilitate communication. The pioneer use of PORs for each individual patient enables personalized analytics sustaining the dialog between neurologists, patients and caregivers with quantified evidence.

Standard Dose Weekly Intramuscular Beta Interferon-1a May Be Inadequate for Some Patients with Multiple Sclerosis: A 19-Year Clinical Experience Using Twice a Week Dosage.

IntroductionResults from several clinical trials suggest there is a dose–response effect for beta interferon-1a (INFβ1a) in multiple sclerosis (MS).MethodsOur objective was to confirm these results through a retrospective analysis of patients with MS who had breakthrough disease (BD) on intramuscular (IM) INFβ1a (Avonex®) once per week (QW), who were switched to twice per week (BIW) IM INFβ1a between 1995 and 2015. The primary outcome measure was no further BD for at least 24 months. A secondary outcome measure was decrease in mean percentage of disease activity over time. BD was defined as continued relapses, new T2 or enhanced lesions on magnetic resonance imaging (MRI) of the brain, or worsening of the Expanded Disability Status Scale (EDSS) or the neurological examination.ResultsAmong 92 patients on QW IM INFβ1a, 53 patients with BD were switched to BIW IM INFβ1a. Of these 53 patients, 44 had adequate follow-up for at least 2 years. Twenty-three of these had no further BD for 24 months or more (range 24–192 months). Beta interferon neutralizing antibody testing was negative in 19 patients. An intent-to-treat analysis of the uncensored data from 52 switched patients also supported a treatment benefit.ConclusionFor patients with MS having breakthrough disease on QW INFβ1a, switching to more frequently administered INFβ may be an option. Advantages to using IM INFβ1a for this include no skin reactions and a lower incidence of neutralizing antibodies. Further pragmatic, observational, larger-group studies comparing treatment with Avonex® and higher dosed IM INFβ1a, such as the recently FDA-approved IM peginterferon beta-1a, may be indicated.

Comparison of Pharmacokinetic Profiles and Safety Outcomes with Peginterferon Beta-1a Administration in Black/African American and White Participants (P4-4.009)

Comparison of Pharmacokinetic Profiles and Safety Outcomes with Peginterferon Beta-1a Administration in Black/African American and White Participants (P4-4.009)

FACTORS ASSOCIATED WITH SWITCHING FROM INJECTABLE TO ORAL DISEASE MODIFYING AGENTS AMONG PATIENTS WITH MULTIPLE SCLEROSIS

BackgroundSince the introduction of oral disease-modifying agents (DMA) in 2010, the treatment options for multiple sclerosis (MS) have changed significantly. There is limited information regarding the factors associated with switching to oral DMA among prevalent injectable DMA users. ObjectiveThis study evaluated the factors associated with switching to oral DMAs among prevalent injectable DMA users with MS. MethodsA retrospective observational cohort study using the TriNetX electronic medical records (EMR) data was conducted among patients with MS. The study included prevalent injectable DMA users with at least two injectable DMA (interferon beta-1a, interferon beta-1b, peginterferon beta-1a, or glatiramer acetate) prescription records within 6 months between September 2010 and May 2018. The second injectable DMA prescription date was considered as the index date. Switching was defined as any oral DMA prescription record (fingolimod, dimethyl fumarate, or teriflunomide) within 12 months after the index date. Patients with any infusion DMA prescription after the first injectable DMA prescription, and those less than 18 years of age were excluded from the study. The Andersen Behavioral Model was used as the conceptual framework to identify predisposing, enabling, and need factors measured during the 1-year baseline period before the index date. A multivariable logistic regression model was used to examine the predisposing (age, sex, race, and ethnicity), enabling (time-period), and need factors (comorbidities, MS symptoms, MS-related medication, and healthcare utilization) associated with switching from injectable to oral DMAs. ResultsAmong 2,943 prevalent injectable users included in this study, 8.09% (n=238) patients switched to oral DMAs. Patients who switched to oral DMAs were primarily younger adults aged 18-44 years (64.29%), females (82.77%), had sensory and visual symptoms, and had corticosteroid utilization during the one-year look-back period compared to non-switchers. Results from multivariable logistic regression model revealed that middle-aged adults (45-64 years, adjusted odds ratio [aOR]: 0.43, 95% Confidence Interval [CI]: 0.32-0.58), old adults (≥65 years, aOR: 0.30, 95% CI: 0.13-0.66) and men (aOR: 0.67, 95% CI: 0.47-0.96) were associated with decreased odds of switching to oral DMAs. Presence of MS-related sensory symptoms (aOR: 1.52, 95% CI: 1.07-2.16), visual symptoms (aOR: 1.59, 95% CI: 1.10-2.31), and corticosteroids usage (aOR: 1.44, 95% CI: 1.04-1.98) were associated with increased odds of switching to oral DMAs. ConclusionThe study found that about one in twelve prevalent injectable DMA users switched to oral DMA. Both demographic and clinical factors were associated with switching to oral DMAs. Further research is needed to evaluate the outcomes of switching to inform treatment decisions for MS management.

Peginterferon beta-1a concentrations in breast milk of lactating multiple sclerosis patients

BackgroundPeginterferon beta-1a is an interferon beta-1a formulation that has been pegylated, resulting in a longer half-life than other interferon beta formulations. We examined concentrations of peginterferon beta-1a in breast milk of lactating patients with multiple sclerosis (MS) receiving peginterferon beta-1a as their postpartum disease-modifying therapy. MethodsAfter completion of titration to a full dose of peginterferon beta-1a and following a single full dose peginterferon beta-1a injection (125 µg), breast milk samples (≥10 mL) were collected by 5 women on days 1–14 post injection. Peginterferon beta-1a concentrations in breast milk samples were measured by a qualified enzyme-linked immunosorbent assay (detection threshold: 15 pg/mL). Mean and median daily concentrations and median maximum concentration (Cmax), time of Cmax (Tmax), time of last measurable concentration (Tlast), area under the concentration-time curve (AUClast), and relative infant dose (RID) were determined. ResultsAfter receiving a single full dose peginterferon beta-1a injection, the maximum breast milk concentration recorded in an individual patient was 126.2 pg/mL (0.00013 µg/mL) on day 6. The remaining patients all had maximum breast milk concentrations <72 pg/mL. The geometric mean of Cmax was 48.9 pg/mL and the median Tmax and Tlast were 4 and 7 days, respectively. The median AUClast was 210.9 day*pg/mL. Among the 5 study patients, the mean breast milk concentration across all study days was 35.95 pg/mL, with an estimated RID of 0.0054% of the maternal dose. ConclusionMinimal concentrations of peginterferon beta-1a were detected in the breast milk samples. These findings may be useful for clinicians considering postpartum MS treatment options.

Early treatment responses to peginterferon beta-1a are associated with longer-term clinical outcomes in patients with relapsing-remitting multiple sclerosis: Subgroup analyses of ADVANCE and ATTAIN

BackgroundEarly intervention with well-tolerated disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) is recommended in order to delay disease progression, reduce neurologic damage, preserve brain volume, and optimize long-term patient outcomes. Lack of conversion of new/newly enlarging T2 (NET2) or gadolinium-enhancing (Gd+) lesions to chronic hypointensities (black hole conversion) and achievement of no evidence of disease activity (NEDA) early in the course of treatment are considered potential indicators of treatment effect and predictors of longer-term clinical outcomes. MethodsPatients with RRMS who were treated with peginterferon beta-1a in the 2-year ADVANCE phase 3 clinical trial (NCT0090639) and its 2-year open-label extension study, ATTAIN (NCT01332019), were grouped as newly diagnosed (diagnosed ≤1 year prior to enrollment and DMT naive) or non–newly diagnosed. For analyses of the impact of early treatment and disease activity control, the newly diagnosed and non–newly diagnosed subgroups were further divided based on whether they initiated peginterferon beta-1a every 2 weeks (Q2W) starting in study year 1 (continuously treated) or peginterferon beta-1a Q2W or every 4 weeks in study year 2 (delayed treatment). Patient subgroups were evaluated for conversion of NET2 or Gd+ lesions to persistent black holes (PBHs), brain atrophy (percentage change in whole brain volume [WBV]), achievement of NEDA composite outcomes, and the association of these disease activity measures with longer-term clinical outcomes (annualized relapse rate [ARR] and confirmed disability worsening [CDW]). ResultsAt 2 years, significantly fewer PBHs developed from NET2 lesions or Gd+ lesions in newly diagnosed and non–newly diagnosed patients continuously treated with peginterferon beta-1a than in the corresponding delayed-treatment groups (all p<0.0001). Percentage decrease in WBV from 6 months (rebaselined) to 2 years was significantly lower for newly diagnosed and non–newly diagnosed patients who received continuous peginterferon beta-1a treatment than for patients who received delayed treatment (both p ≤ 0.0442). In study year 1, a higher proportion of newly diagnosed and non–newly diagnosed patients treated with peginterferon beta-1a than those treated with placebo achieved NEDA (newly diagnosed: 28.3% vs 13.5% [p = 0.0010]; non–newly diagnosed: 40.8% vs 15.8% [p<0.0001]). NEDA rates remained stable over study years 2–4 for the newly diagnosed (range: 50.0%–53.9%) and non–newly diagnosed (range: 54.4%–57.0%) subgroups. Patients without PBH conversion had significantly lower ARR at 2 years (newly diagnosed: p = 0.0109; non–newly diagnosed: p = 0.0044) and a lower proportion of patients with 12-week CDW at 2 years (newly diagnosed: p = 0.2787; non–newly diagnosed: p = 0.0045) than the corresponding patient subgroups with PBH conversion. Patients who achieved NEDA in ADVANCE (study years 1–2) had a significantly lower ARR in ATTAIN (study years 3–4) than patients who did not achieve NEDA (newly diagnosed, p = 0.0003; non–newly diagnosed, p = 0.0001). Over 4 years, safety outcomes did not differ for the newly diagnosed and non–newly diagnosed patient subgroups. ConclusionsThese results indicate that newly diagnosed and non–newly diagnosed patients treated continuously with peginterferon beta-1a Q2W experienced better disease control over time than those who received delayed treatment. Patients with NEDA or evidence of less radiological disease activity in the first 2 years of treatment had better longer-term clinical outcomes than those with evidence of greater disease activity.

Safety and clinical effectiveness of peginterferon beta-1a for relapsing multiple sclerosis in the real-world setting: Interim results from the Plegridy Observational Program

BackgroundThe Plegridy Observational Program (POP) is an ongoing, 5-year, phase 4 real-world study of the safety and effectiveness of subcutaneous peginterferon beta-1a in patients with relapsing multiple sclerosis (RMS). MethodsThis interim analysis from POP assessed the safety and effectiveness of peginterferon beta-1a, including subgroup analyses of patients aged < 50 and ≥ 50 years, newly diagnosed and non–newly diagnosed patients, and new and experienced peginterferon beta-1a users. ResultsA total of 1208 patients enrolled in POP. Mean (standard deviation) peginterferon treatment duration in the overall population was 757.0 (529.5) days. The overall incidence of treatment-emergent adverse events (AEs) was 65.5%, and the incidence was higher in new than experienced peginterferon beta-1a users (78.1 vs 52.4%). The overall incidence of treatment-emergent serious AEs was 7.6%, and the incidence was lower in younger than older patients (5.8 vs 11.1%). No new or unexpected safety signals were reported. Overall treatment discontinuation due to AEs occurred in 20.7% of patients, with a higher proportion of new than experienced peginterferon beta-1a users (27.0 vs 14.2%) discontinuing treatment due to AEs. Flu-like symptoms and injection site reactions were significant predictors of time to treatment discontinuation. The adjusted annualized relapse rate (ARR) was 0.12 (95% confidence interval 0.11–0.13) in the overall population and was similar across all subgroups. In the overall population at 4 years, 79.1% of patients were relapse free, the estimated cumulative proportion of patients with confirmed disability worsening was 1.8%, and > 67% of patients achieved clinical no evidence of disease activity (NEDA). ConclusionsSafety data of patients enrolled in POP are consistent with the established clinical safety profile of peginterferon beta-1a. In addition, the low ARR and high proportion of patients achieving clinical NEDA at 4 years across all subgroups indicates the effectiveness of peginterferon beta-1a in treating RMS in real-world clinical settings.

Disease-modifying agents for multiple sclerosis and the risk for reporting cancer: A disproportionality analysis using the US Food and Drug Administration Adverse Event Reporting System database.

While the efficacy of disease-modifying therapies (DMTs) for patients with multiple sclerosis (MS) is established, little is known about their long-term safety. Cancer-risk after DMT use remains unclear. This study aimed to investigate whether the prescription of DMTs for patients with MS increases the risk of reporting cancer. Data from the Food and Drug Administration Adverse Event Reporting System were extracted from 2004 to 2020. After data cleaning, the crude and adjusted reported odds ratios (cROR and aROR) for cancer were calculated for DMTs with Interferon beta-1a as the reference drug. Sensitivity analyses investigated the group of reports with multiple registered DMTs, the effect of indication restriction and the results when using the rest of the DMTs as reference. For malignant tumours, aROR (95% confidence interval [CI]) values were Cladribine 0.46 (0.18-0.95), Dimethyl fumarate 0.30 (0.27-0.34), Fingolimod 0.61 (0.53-0.70), Glatiramer 0.50 (0.43-0.58), Alemtuzumab 0.84 (0.64-1.08), Interferon beta-1b 0.49 (0.42-0.56), Natalizumab 0.36 (0.34-0.39), Ocrelizumab 0.48 (0.29-0.74), Peginterferon beta-1a 0.35 (0.26-0.48), Siponimod 0.89 (0.47-1.54) and Teriflunomide 0.25(0.21-0.30) adjusted to age, gender and concomitant medications. In the sensitivity analysis, when the rest of the drugs were used as a reference, Interferon beta-1a and Peginterferon beta-1a had aROR (95% CI) 2.60 (2.47-2.74, P < .001) and Alemtuzumab had aROR 1.47 (1.13-1.88, I = .003). No safety signal for increased cancer risk was detected among the approved DMTs. A potential safety signal detected in the sensitivity analysis concerning Interferon beta-1a and Alemtuzumab requires further evaluation with more robust evidence.

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.

PurposeThe 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 MethodsThe 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.ResultsIn 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.ConclusionAlthough 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.

Multicenter Interventional Phase IV Study for the Assessment of the Effects on Patient's Satisfaction of Peg IFN Beta-1a (Pre-filled Pen) in Subjects With Relapsing-Remitting Multiple Sclerosis Unsatisfied With Other Injectable Subcutaneous Interferons (PLATINUM Study).

Subcutaneous (SC) interferons beta (IFN-beta) are effective therapies for the treatment of relapsing–remitting multiple sclerosis (RRMS). Factors such as dosing schedule, needle intolerance/fatigue, and side effects may impact patient satisfaction with treatment. Improvement of patient satisfaction may increase the adherence to treatment and the patient quality of life. This study was aimed at evaluating the impact of switching to “Peginterferon beta-1a (Peg-IFN beta-1a)” in patients with RRMS unsatisfied with other SC interferons. The multicenter, open-label, phase IV PLATINUM study was conducted in 32 Italian centers. The primary endpoint was changes from baseline in the score of a convenience satisfaction domain of the TSQM-9 questionnaire at 12 weeks. The secondary endpoints were patients' global satisfaction, short-term adherence to treatment, satisfaction with the injection system, effect on fatigue, disease activity, and patient inability score. A total of 193 patients were enrolled and 166 (86%) completed the study, receiving Peg-IFN beta-1a for 24 weeks. Patients switching to Peg-IFN beta-1a from other SC interferons reported a significant improvement (p < 0.001) of Convenience Score and all other scores of the TSQM-9 questionnaire at 12 and 24 weeks (p < 0.001). Peg IFN beta-1a attained very high adherence to the treatment (92 and 86% at 12 and 24 weeks, respectively) with a stable annualized relapse rate (ARR). At 24 weeks, 94% of the participants were relapse free. Adverse events (AEs), recorded on 82 patients (42%), were mild or moderate. The most common AE was flu-like syndrome (29.2%). Patients switching from SC IFN beta therapy to Peg IFN beta-1a showed high treatment satisfaction with a positive safety profile, comparable with that of other currently approved first-line injectable SC interferons. This study suggests that Peg IFN beta-1a might represent a treatment choice to improve adherence in RRMS patients unsatisfied with other SC interferons.

Characteristics and clinical outcomes of underserved minority patients with multiple sclerosis treated with peginterferon beta-1a or intramuscular interferon beta-1a in MS PATHS (2392)

Characteristics and clinical outcomes of underserved minority patients with multiple sclerosis treated with peginterferon beta-1a or intramuscular interferon beta-1a in MS PATHS (2392)

Real-world propensity score comparison of treatment effectiveness of peginterferon beta-1a vs. subcutaneous interferon beta-1a, glatiramer acetate, and teriflunomide in patients with relapsing-remitting multiple sclerosis

BackgroundMultiple disease-modifying therapies (DMTs) have been approved by the U.S. Food & Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS). In separately conducted clinical trials, peginterferon beta-1a, subcutaneous interferon beta-1a (SC IFN beta-1a), glatiramer acetate (GA), and teriflunomide have demonstrated efficacy for reducing relapses. No head-to-head phase III clinical trials have directly compared the treatment efficacy of peginterferon beta-1a with these other DMTs. ObjectivesA propensity score-based comparison was conducted of the treatment effectiveness of peginterferon beta-1a vs. SC IFN beta-1a, GA, and teriflunomide among patients with RRMS identified from a large U.S. administrative healthcare claims database. MethodsAdult patients (18-65 years of age) who had ≥1 claim for an MS diagnosis between November 2013 and June 2017 and ≥1 claim for peginterferon beta-1a, SC IFN beta-1a, GA, or teriflunomide between November 1, 2014, and March 31, 2017 were identified from the IBM® MarketScan® Commercial database. The index date was the first claim of a patient's DMT initiated. Only patients who had ≥12 months of insurance enrollment pre-index (baseline period) and ≥90 days post-index (variable length follow-up period) were included. Patients were grouped into cohorts according to the index DMT. Patient demographics and clinical characteristics were evaluated. Propensity score matching (PSM) was separately conducted for pairwise comparisons of treatment effectiveness between peginterferon beta-1a and the other DMT cohorts. During the post-index follow-up period, annualized relapse rate (ARR; relapse defined as hospitalization or outpatient visit with subsequent treatment), annualized number and length of inpatient stays, and the number of claims for durable medical equipment were evaluated. ResultsWith PSM, there were 325 patients (mean age: 46.0 years) in the peginterferon beta-1a cohort compared to 967 (mean age: 46.9 years) in the SC IFN beta-1a cohort; likewise there were 564 patients (mean age: 47.4 years) in the peginterferon beta-1a and 1688 (mean age: 47.6 years) in the GA cohort; and finally there were 584 patients (mean age: 49.1 years) in the peginterferon beta-1a cohort and 1742 (mean age: 49.0 years) in the teriflunomide cohort. During the post-index follow-up period, the ARR did not significantly differ between the peginterferon beta-1a and SC IFN beta-1a cohorts; the ARR was lower among patients treated with peginterferon beta-1a than among those treated with GA (Least squares mean [LSM] estimate: 0.25 vs. 0.31; LSM ratio: 0.809; P=0.027) or teriflunomide (LSM estimate: 0.26 vs. 0.37; LSM ratio: 0.704; P<0.001). The annualized mean number and length of inpatient stays and the mean number of claims for durable medical equipment during the post-index follow-up did not differ between the matched peginterferon beta-1a and GA cohorts nor the peginterferon beta-1a and teriflunomide cohorts. ConclusionIn this real-world comparative analysis of patients with similar patient characteristics, treatment with peginterferon beta-1a was associated with lower ARRs than treatment with either GA or teriflunomide; ARRs did not differ among patients treated with SC IFN beta-1a. Also, all other measured secondary outcomes did not differ between study cohorts. These real-world data may help support decision-making in the treatment of patients with RRMS.

Global Peginterferon Beta-1a Tolerability Management Best Practices: A Nurse-Focused Delphi Approach.

IntroductionInjection site reactions (ISRs) and flu-like symptoms (FLS) are common in patients with relapsing forms of multiple sclerosis (MS) treated with peginterferon beta-1a. The purpose of this Delphi analysis was to explore peginterferon beta-1a discontinuation rates across MS treatment centers, to obtain consensus on effective mitigation and management strategies for ISRs and FLS, and to identify areas where additional training and education for nurses and patients could improve treatment outcomes.MethodsIn this modified Delphi process, an international steering committee of eight MS-certified nurses developed two rounds of surveys, which were completed by 262 and 188 MS nurses, respectively, representing nine countries.ResultsOn average, nurses reported that 25% and 30% of patients treated with peginterferon beta-1a experienced ISRs and FLS, respectively. Discontinuation due to severe ISRs or FLS was most common in the first 6 months of treatment, yet follow-up visits typically took place 6 months after peginterferon beta-1a initiation. Preferred management strategies for ISRs included nonsteroidal anti-inflammatory drugs and rotation of the injection site, whereas preferred management strategies for FLS included acetaminophen/paracetamol and hydration/nutrition. Most nurses (77%) agreed that additional education and training on ISR and FLS management would bolster their confidence in treating patients with these symptoms.ConclusionDelphi respondents reached consensus on ISR and FLS management strategies, which can help to inform treatment decisions. The results of this global Delphi analysis indicate that management of ISRs and FLS could be improved with more frequent follow-up visits and individualized training and education.

COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies.

BackgroundDisease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS (PwMS).ObjectiveThe objective of this study was to describe the overall risk of coronavirus disease 2019 (COVID-19) infection, severe disease course, and potential population-level predictors of COVID-19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies.MethodsThe IBM® Explorys electronic health record database of > 72,000,000 patients from US healthcare networks identified patients with MS or SLE, with and without polymerase chain reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths among DMT classes were compared using logistic regression (adjusted for age, sex, body mass index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-19 reports for Biogen MS therapies were extracted and described from Biogen’s Global Safety Database.Results30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p < 0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine.ConclusionsComorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen MS therapies were consistent with the Explorys database and MS literature, illustrating the replicability and power of this approach.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-021-00804-1.