Serum neurofilament light-chain levels and long-term treatment outcomes in relapsing-remitting multiple sclerosis patients: A post hoc analysis of the randomized CombiRx trial

Article

作者: Rudick, Richard A ; Lublin, Fred D ; Fisher, Elizabeth ; de Moor, Carl ; McFarland, Henry ; Singh, Carol M ; Koster, Thijs ; Wolinsky, Jerry S ; Jacobson, Steven ; Naylor, Maria L ; Cutter, Gary

Background CombiRx was a randomized, double-blind, placebo-controlled phase 3 trial in treatment-naive relapsing-remitting multiple sclerosis (RRMS) patients randomized to intramuscular interferon beta-1a (IM IFN beta-1a), glatiramer acetate (GA), or both therapies. Objective This analysis investigated changes in serum neurofilament light-chain (sNfL) levels in response to treatment and assessed baseline sNfL as a predictor of relapse. Methods RRMS patients treated with IM IFN beta-1a 30 µg weekly + placebo (n = 159), GA 20 mg/mL daily + placebo (n = 172), or IM IFN beta-1a + GA (n = 344) were included. A linear mixed model compared sNfL values over time. Cox regression models analyzed baseline sNfL and gadolinium-enhancing (Gd+) lesions as predictors of relapse. Results In all treatment arms, the proportion of patients with sNfL ≥16 pg/mL decreased significantly from baseline to 6 months and was maintained at 36 months. A significantly higher percentage of patients with both baseline sNfL ≥16 pg/mL and ≥1 Gd+ lesion experienced relapses within 90 days compared to patients with sNfL <16 pg/mL and/or no Gd+ lesions. Conclusion sNfL levels were reduced within 6 months and remained low at 36 months. Results suggest that the combination of lesion activity and sNfL was a stronger predictor of relapse than either factor alone.

2021-12-01·BMC Neurology4区 · 医学

Acute posterior reversible encephalopathy syndrome (PRES) in setting of interferon-beta use: case presentation with reduction of edema in 72 h after cessation of interferon-beta therapy with sub-clinical inflammation

4区 · 医学

ArticleOA

作者: Robertson, David ; Counts, Christopher ; Bjurström, Martin F ; Dietz, Nicholas ; Williams, Brian J ; Mufti, Zarmina ; Brown, Randal ; Yousaf, Muhammed

AbstractBackgroundPosterior reversible encephalopathy syndrome (PRES) represents a transient change in mental status with associated vasogenic edema of cortical and subcortical brain structures. It is often attributed to multifactorial etiology including hypertension and altered hemodynamics and disruption of vessel integrity. Patients with autoimmune disease and certain immune modulator therapies are at greater risk.Case presentationA 54-year-old female with past medical history of well-controlled multiple sclerosis on interferon-beta since 2013, presented with witnessed tonic colonic seizure. She also was noted to demonstrate left gaze deviation and left-sided hemiparesis. MRI fluid-attenuated inversion recovery sequence showed hyperintensity of the subcortical U fibers, concentrated in the occipital, parietal lobes and frontal lobes. Systolic blood pressure was 160 mmHg on arrival. The patient was started on seizure prophylxis and Interferon beta was discontinued. The patient’s mentation, seizures and hemiapresis significantly improved in next 72 h with tight blood pressure control, and had notble improvement on MRI imaging and inflammatory markers. Lumbar puncture CSF results were devoid of infectious and autoimmune pathology.ConclusionsA middle-aged female with multiple sclerosis who was on chronic IFN-beta presented to the emergency room with a witnessed tonic-clonic seizure, with MRI T2 FLAIR imaging consistent with PRES. She had notable clinical improvement with decreased edema on imaging and improved inflammatory markers 72 h after cessation of IFN-beta therapy.

2021-11-02·Journal of Community Hospital Internal Medicine Perspectives

Efficacy of subcutaneous interferon-beta in COVID-19: a meta-analysis and systematic review

Article

作者: Asif, Abuzar A. ; Syed, Salman B. ; Singhal, Malay ; Tharoor, Manisha ; Vanka, Varun ; Rathore, Urvashi ; Hussain, Habiba ; Rangwala, Umme Salma ; Senthil Kumaran, Sriviji ; Chatterjee, Tulika

Type 1 interferons, especially interferon-beta, has been reported to be effective in COVID-19 patients in multiple randomized controlled trials. The aim of our meta-analysis and systematic review is to assess efficacy of subcutaneous IFN-beta in regards to mortality and discharge rate. Prospective, retrospective and randomized controlled trials were included. Primary outcomes measured were 28-day mortality and discharge rate. Secondary outcomes measured were mean hospital stay and post-intervention intubation rate. A thorough literature search was conducted in Medline, PubMed, Ovid journals, Google Scholar, and Cochrane Central Register of Controlled Trials & Database of Systematic Reviews from 1 April 2020 to 28 February 2021. Relative risk was calculated using both the Mantel-Haenszel method (fixed-effects model) and DerSimonian Laird method (random effects model). The heterogeneity among studies was tested using Cochran's Q test, based upon inverse variance weights. 7 studies were included in the meta-analysis and systematic review. The IFN-beta group did not improve the 28-day mortality (RR = 1.276; 95% CI: 1.106-1.472, p = 0.001) or the discharge rate (RR = 0.906; 95% CI = 0.85-0.95, p = < 0.001). The mean hospital stay was 11.95± 2.5 days in the interferon-beta group and 11.43 ± 3.74 days in the traditional treatment group. Likewise, interferon-beta did not add any advantage to post-intervention intubation rate (RR = 0.92; 95% CI = 0.7841-1.0816, p = 0.3154). Our findings revealed that use of subcutaneous interferon-beta is futile in COVID-19.

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