Respiratory Trials·org

Interstitial lung disease · Immunosuppression in connective tissue ILD

EVER-ILD

Rituximab and mycophenolate mofetil in interstitial lung disease

EVER-ILD trial design and results
Design Randomised, double-blind, placebo-controlled trial
Treatment Rituximab plus mycophenolate mofetil
Control Placebo plus mycophenolate mofetil
Population 122 patients with interstitial lung disease and a non-specific interstitial pneumonia pattern
Follow-up 6 months
Primary endpoint Change from baseline in percentage predicted FVC at 6 months
Result FVC change +1.60% predicted with rituximab plus mycophenolate versus -2.01% with mycophenolate alone — between-group difference 3.60 (95% CI 0.41 to 6.80, p=0.0273). Progression-free survival favoured the combination (HR 0.47, 0.23 to 0.96, p=0.03). Serious adverse events occurred in 41% versus 39%, with more viral infections on rituximab.
Secondary endpoints Progression-free survival, serious adverse events, infection

Combination of rituximab and MMF was superior to MMF alone in patients with ILD and a NSIP pattern. The use of this combination must take into consideration the risk of viral infection.

The trial authors, in the published abstract

How it has aged

One of the few positive immunosuppression trials in ILD, and a useful reminder that the antifibrotic story of INBUILD does not apply everywhere: inflammatory NSIP still responds to immunosuppression. Small, short, and the infection signal is the thing to weigh.

Publications

Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial

Mankikian J, Caille A, Reynaud-Gaubert M, et al. Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial. Eur Respir J 2023 Jun;61(6).

  • FVC improved by 3.6 percentage points relative to mycophenolate alone
  • Progression-free survival more than halved in hazard
  • More viral infections with rituximab