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Interferons and Multiple Sclerosis: Lessons from 25 Years of Clinical and Real-World Experience with Intramuscular Interferon Beta-1a (Avonex).

ABSTRACT: Recombinant interferon (IFN) β-1b was approved by the US Food and Drug Administration as the first disease-modifying therapy (DMT) for multiple sclerosis (MS) in 1993. Since that time, clinical trials and real-world observational studies have demonstrated the effectiveness of IFN therapies. The pivotal intramuscular IFN β-1a phase III trial published in 1996 was the first to demonstrate that a DMT could reduce accumulation of sustained disability in MS. Patient adherence to treatment is higher with intramuscular IFN β-1a, given once weekly, than with subcutaneous formulations requiring multiple injections per week. Moreover, subcutaneous IFN β-1a is associated with an increased incidence of injection-site reactions and neutralizing antibodies compared with intramuscular administration. In recent years, revisions to MS diagnostic criteria have improved clinicians' ability to identify patients with MS and have promoted the use of magnetic resonance imaging (MRI) for diagnosis and disease monitoring. MRI studies show that treatment with IFN β-1a, relative to placebo, reduces T2 and gadolinium-enhancing lesions and gray matter atrophy. Since the approval of intramuscular IFN β-1a, a number of high-efficacy therapies have been approved for MS, though the benefit of these high-efficacy therapies should be balanced against the increased risk of serious adverse events associated with their long-term use. For some subpopulations of patients, including pregnant women, the safety profile of IFN β formulations may provide a particular benefit. In addition, the antiviral properties of IFNs may indicate potential therapeutic opportunities for IFN β in reducing the risk of viral infections such as COVID-19.

SUBMITTER: Cohan SL

PROVIDER: S-EPMC8258741 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionCutaneous adverse events (AEs) have been observed in clinical studies of daclizumab high-yield process (HYP) in relapsing-remitting multiple sclerosis (RRMS). Here, we report cutaneous AEs observed in the randomized, double-blind, active-comparator DECIDE study (ClinicalTrials.gov identifier, NCT01064401).MethodsDECIDE was a randomized, double-blind, active-controlled phase 3 study of daclizumab HYP 150 mg subcutaneous every 4 weeks versus interferon (IFN) beta-1a 30 mcg intramuscular (IM) once weekly in RRMS. Treatment-emergent AEs were classified and recorded by investigators. Investigators also assessed the severity of each AE, and whether it met the criteria for a serious AE. Cutaneous AEs were defined as AEs coded to the Medical Dictionary for Regulatory Activities System Organ Class of skin and subcutaneous tissue disorders. The incidence, severity, onset, resolution, and management of AEs were analyzed by treatment group.ResultsCutaneous AEs were reported in 37% of daclizumab HYP-treated patients and 19% of IFN beta-1a-treated patients. The most common investigator-reported cutaneous AEs with daclizumab HYP were rash (7%) and eczema (4%). Most patients with cutaneous AEs remained on treatment (daclizumab HYP, 81%; IM IFN beta-1a, 90%) and had events that were mild or moderate (94% and 98%) and subsequently resolved (78% and 82%). Most patients with cutaneous AEs did not require treatment with corticosteroids or were treated with topical corticosteroids (daclizumab HYP, 73%; IM IFN beta-1a, 81%). Serious cutaneous AEs were reported in 14 (2%) daclizumab HYP patients and one (<1%) IM IFN beta-1a patient.ConclusionThere was an increased risk of cutaneous AEs with daclizumab HYP. While physicians should be aware of the potential for serious cutaneous AEs, the typical cutaneous AEs were mild-to-moderate in severity, manageable, and resolved over time.FundingBiogen and AbbVie Biotherapeutics Inc.Trial registrationClinicalTrials.gov identifier, NCT01064401.

Project description:This study aimed to review and evaluate our experience in 750 patients, who underwent transhiatal esophagectomy (THE) and analyze our data. Special attention was paid to some strategies, which we developed in the course of time, regarding the postoperative management of these patients and formulation of improved guidelines.This is a retrospective analysis of all THE operations performed between January 1981 until May 2007 in 750 patients: 60 patients (8%) had benign lesions, while 690 (92%) had malignant ones (5.2% of malignancies were located in the upper esophagus, 7.4% in the middle esophagus, 19% in the lower esophagus, and 68.4% at the cardioesophageal junction). THE and esophageal reconstruction were performed at the same operation in all patients. The stomach was our esophageal substitute of first choice with the colon and jejunum being acceptable alternatives in patients with prior gastric surgery and those necessitating synchronous gastrectomy for cancer invasion. A gastric tube was used as an esophageal substitute in 624 patients (83.2%), the whole stomach in 70 (9.4%), the colon in 43 (5.73%), and a jejunal loop in 13 (1.73%).The overall in-hospital mortality rate was 2.93% (22 patients). There was no intraoperative death. Major complications included atelectasis or pneumonia (4.8%), pleural effusion (22.7%), myocardial infarction (0.5%), recurrent laryngeal nerve paralysis (1.33%), and three tracheal lacerations (0.4%). The anastomotic leak rate decreased gradually over time from 29.4% to 11.1% in the last 6 years. The average intraoperative blood loss was 315 ml and 82% of the patients did not receive any blood transfusion. Late functional results were good or excellent in 93%. The average length of hospital stay was 11 days and intensive care unit stay was 2.3 days. The actuarial 5-year survival rate after THE for carcinoma was 21%.THE is a safe and effective method of esophageal resection with low morbidity and mortality rates and good functional results when performed by experienced surgeons. We believe that our strategies concerning the way of dissecting the cervical esophagus, avoidance of performing pyloromyotomy, the delayed removal of the cervical drain and the delayed advance to oral feeding have reduced, noticeably, morbidity and mortality in our series.

Project description:In Brazil, inclusion and exclusion of health technologies within the Unified Health System (SUS) is the responsibility of the National Committee for Health Technology Incorporation (CONITEC). A recent Cochrane systematic review demonstrated that intramuscular interferon beta 1a (IFN-?-1a-IM) was inferior to the other beta interferons (IFN-?s) for multiple sclerosis (MS). As a result, CONITEC commissioned an analysis to review possible disinvestment within SUS. The objective of this paper is to describe the disinvestment process for IFN-?-1a-IM in Brazil. The first assessment comprised a literature review and mixed treatment comparison meta-analysis. The outcome of interest was the proportion of relapse-free patients in 2 years. This analysis confirmed the inferiority of IFN-?-1a-IM. Following this, CONITEC recommended disinvestment, with the decision sent for public consultation. More than 3000 contributions were made on CONITEC's webpage, most of them against the preliminary decision. As a result, CONITEC commissioned a study to assess the effectiveness of IFN-?-1a-IM among Brazilian patients in routine clinical care. The second assessment involved an 11-year follow-up of a non-concurrent cohort of 12,154 MS patients developed by deterministic-probabilistic linkage of SUS administrative databases. The real-world assessment further demonstrated that IFN-?-1a-IM users had a statistically higher risk of treatment failure, defined as treatment switching or relapse treatment or death, with the assessment showing that IFN-?-1a-IM was inferior to the other IFN-?s and to glatiramer acetate in both direct and indirect analysis. In the drug ranking with 40,000 simulations, IFN-?-1a-IM was the worst option, with a success rate of only 152/40,000. Following this, CONITEC decided to exclude the intramuscular presentation of IFN-? from the current MS treatment guidelines, giving patients who are currently on this treatment the option of continuing until treatment failure. In conclusion, we believe this is the first example of this new disinvestment process in action, providing an exemplar for other treatments in Brazil as well as other countries.

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Interferons and Multiple Sclerosis: Lessons from 25 Years of Clinical and Real-World Experience with Intramuscular Interferon Beta-1a (Avonex).

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