IFN-α kinoid in systemic lupus erythematosus: results from a phase IIb, randomised, placebo-controlled study

Ann Rheum Dis. 2020 Mar;79(3):347-355. doi: 10.1136/annrheumdis-2019-216379. Epub 2019 Dec 23.

Abstract

Objective: To evaluate the efficacy and safety of the immunotherapeutic vaccine interferon-α kinoid (IFN-K) in a 36-week (W) phase IIb, randomised, double-blind, placebo (PBO)-controlled trial in adults with active systemic lupus erythematosus (SLE) despite standard of care.

Methods: Patients with SLE (185) with moderate to severe disease activity and positive interferon (IFN) gene signature were randomised to receive IFN-K or PBO intramuscular injections (days 0, 7 and 28 and W12 and W24). Coprimary endpoints at W36 were neutralisation of IFN gene signature and the BILAG-Based Composite Lupus Assessment (BICLA) modified by mandatory corticosteroid (CS) tapering.

Results: IFN-K induced neutralising anti-IFN-α2b serum antibodies in 91% of treated patients and reduced the IFN gene signature (p<0.0001). Modified BICLA responses at W36 did not statistically differ between IFN-K (41%) and PBO (34%). Trends on Systemic Lupus Erythematosus Responder Index-4, including steroid tapering at W36, favoured the IFN-K and became significant (p<0.05) in analyses restricted to patients who developed neutralising anti-IFN-α2b antibodies. Attainment of lupus low disease activity state (LLDAS) at W36 discriminated the two groups in favour of IFN-K (53% vs 30%, p=0.0022). A significant CS sparing effect of IFN-K was observed from W28 onwards, with a 24% prednisone daily dose reduction at W36 in IFN-K compared with PBO (p=0.0097). The safety profile of IFN-K was acceptable.

Conclusions: IFN-K induced neutralising anti-IFN-α2b antibodies and significantly reduced the IFN gene signature with an acceptable safety profile. Although the clinical coprimary endpoint was not met, relevant secondary endpoints were achieved in the IFN-K group, including attainment of LLDAS and steroid tapering.

Trial registration number: NCT02665364.

Keywords: systemic lupus erythematosus; treatment; vaccination.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage
  • Adult
  • Autoantibodies / blood
  • Double-Blind Method
  • Female
  • Humans
  • Immunologic Factors / administration & dosage*
  • Injections, Intramuscular
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / immunology
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Treatment Outcome
  • Withholding Treatment / statistics & numerical data

Substances

  • Adrenal Cortex Hormones
  • Autoantibodies
  • Immunologic Factors
  • Interferon-alpha
  • Interferon-alpha2b

Associated data

  • ClinicalTrials.gov/NCT02665364
  • EudraCT/2015-001341-86