title: Dry Eye Signs and Symptoms Persist During Systemic Neutralization of IL-1β by Canakinumab or IL-17A by Secukinumab.
abstract: OBJECTIVE
  To evaluate whether inhibition of the proinflammatory cytokines IL-1β or IL-17A by canakinumab or secukinumab, respectively, influence the signs and symptoms of dry eye.
  
  
  METHODS
  In a randomized, double-masked, placebo-controlled, outpatient clinical trial, 72 patients with moderate to severe dry eye were randomly assigned in a 1:1:1 ratio to treatment with a single intravenous dose of canakinumab, of secukinumab, or of placebo. Signs and symptoms of dry eye were evaluated on the treatment day and 1 week, 4 weeks, and 8 weeks after treatment. The prespecified primary efficacy endpoint was corneal staining in the study eye 4 weeks after treatment. Secondary endpoints included tear production (Schirmer test), tear film breakup time, conjunctival redness, the ocular surface disease index (OSDI), the frequency of a desire for a topical ocular lubricant, and visual acuity.
  
  
  RESULTS
  Of the 71 patients included in the analysis of safety, the rate of adverse events was similar between treatment groups. The course of corneal staining scores from baseline to 4 weeks, respectively, were for canakinumab 1.46 to 1.33 (P = 0.62 compared with placebo), for secukinumab 1.46 to 1.23 (P = 0.22), and for placebo 1.68 to 1.42. There were no changes in the other measures of efficacy beyond what was within the range expected for stochastic day-to-day variation.
  
  
  CONCLUSIONS
  The results suggest that the inhibition of IL-1β or IL-17A obtained by systemic administration of neutralizing drugs does not influence the severity of dry eye.
authors.affiliation: *Translational Medicine, Novartis Institutes for Biomedical Research, Cambridge, MA; †Biometrics Matters Ltd, Hamilton, New Zealand; and ‡Ophthalmology Research, Novartis Institutes for Biomedical Research, Cambridge, MA.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Grosskreutz
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Hockey
authors.forename: Denise
authors.initials: D
authors.lastname: Serra
authors.forename: Thaddeus P
authors.initials: TP
authors.lastname: Dryja
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D015352:Dry Eye Syndromes / Q000175:diagnosis* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D013666:Tears / Q000502:physiology; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D020381:Interleukin-17; D053583:Interleukin-1beta; C541220:canakinumab; C555450:secukinumab