title: Interleukin-1 Antagonist Anakinra in Amyotrophic Lateral Sclerosis--A Pilot Study.
abstract: Preclinical studies show that blocking Interleukin-1 (IL-1) retards the progression of Amyotrophic Lateral Sclerosis (ALS). We assessed the safety of Anakinra (ANA), an IL-1 receptor antagonist, in ALS patients. In a single arm pilot study we treated 17 ALS patients with ANA (100 mg) daily for one year. We selected patients with dominant or exclusive lower motor neuron degeneration (LMND) presentation, as peripheral nerves may be more accessible to the drug. Our primary endpoint was safety and tolerability. Secondary endpoints included measuring disease progression with the revised ALS functional rating scale (ALSFRSr). We also quantified serum inflammatory markers. For comparison, we generated a historical cohort of 47 patients that fit the criteria for enrollment, disease characteristics and rate of progression of the study group. Only mild adverse events occurred in ALS patients treated with ANA. Notably, we observed lower levels of cytokines and the inflammatory marker fibrinogen during the first 24 weeks of treatment. Despite of this, we could not detect a significant reduction in disease progression during the same period in patients treated with ANA compared to controls as measured by the ALSFRSr. In the second part of the treatment period we observed an increase in serum inflammatory markers. Sixteen out of the 17 patients (94%) developed antibodies against ANA. This study showed that blocking IL-1 is safe in patients with ALS. Further trials should test whether targeting IL-1 more efficiently can help treating this devastating disease.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01277315.
authors.affiliation: Department of Neurology, Charité-University Hospital, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Maier
authors.affiliation: Max-Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Deigendesch
authors.affiliation: Neurology Department, Ulm University, Ulm, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Müller
authors.affiliation: Neurology Department, Ulm University, Ulm, Germany.
authors.forename: Jochen H
authors.initials: JH
authors.lastname: Weishaupt
authors.affiliation: Department of Biostatistics, Coordination Center for Clinical Trials, Charité-University Hospital, Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Krannich
authors.affiliation: Department of Biostatistics, Coordination Center for Clinical Trials, Charité-University Hospital, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Röhle
authors.affiliation: Max-Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Meissner
authors.affiliation: Max-Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Kaaweh
authors.initials: K
authors.lastname: Molawi
authors.affiliation: Department of Neurology, Charité-University Hospital, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Münch
authors.affiliation: Department of Neurology, Charité-University Hospital, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: Holm
authors.affiliation: Department of Neurology, Charité-University Hospital, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Meyer
authors.affiliation: Department of Neurology, Charité-University Hospital, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meyer
authors.affiliation: Max-Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Arturo
authors.initials: A
authors.lastname: Zychlinsky
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000188:drug therapy / Q000378:metabolism; D009142:Musculoskeletal Physiological Phenomena / Q000187:drug effects; D010865:Pilot Projects
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1