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Multicenter Study: Rituximab Promising for Interstitial Pneumonia with Autoimmune Features

Key findings

  • In the first multicenter study of the question, the efficacy and safety of rituximab for treating interstitial pneumonia with autoimmune features was retrospectively examined at Massachusetts General Hospital (n=36) and University of Chicago Medicine (n=14)
  • Similar percentages of patients in the two cohorts stabilized or improved as defined by the composite of clinician global assessment, oxygen requirement, need for unplanned respiratory-related hospitalization and survival at one year
  • Stabilization or improvement of pulmonary function was also similar in the two cohorts after rituximab initiation
  • Adverse events included minor infusion reactions and infections (the relationship between infections and rituximab is unknown because most patients received concomitant glucocorticoid therapy)

In 2015, the European Respiratory Society and American Thoracic Society introduced the diagnostic entity "interstitial pneumonia with autoimmune features" (IPAF). Its classification criteria apply to the many patients with interstitial lung disease (ILD) who have clinical, laboratory or imaging features suggesting an autoimmune inflammatory lung disease but don't meet the criteria for systemic rheumatic disease.

Medical therapy for IPAF is still undefined, but since it's similar to ILD associated with systemic rheumatic diseases, a benefit from immunosuppressive therapy is plausible.

Massachusetts General Hospital's Hyon Choi, MD, program director of the Clinical Epidemiology Program and clinical rheumatologist with the Division of Rheumatology, Allergy and ImmunologySydney B. Montesi, MD, clinician-researcher in the Division of Pulmonary and Critical Care, Kristin M. D'Silva, MD, former research fellow in the Rheumatology Unit, and colleagues recently conducted the largest study to date to examine the efficacy and safety of rituximab for IPAF.

In Rheumatology Advances in Practice, they report similarly positive results at two large academic medical centers.


The researchers identified adults with IPAF who had been treated with rituximab at Mass General Brigham (MGB, 2000–2018) or University of Chicago Medical (UCM, 2006–2019). Rituximab was chosen at the discretion of the treating physician. Its efficacy was evaluated using two co-primary outcomes:

  • A composite of four domains—clinician global assessment, oxygen requirement, need for unplanned respiratory-related hospitalization and survival at one year
  • Change in pulmonary function tests (PFT)—improvement was defined as ≥10% increase in the percentage predicted forced vital capacity (FVC), stability as the percentage predicted FVC within ±10% of initial measurement, and worsening as ≥10% decrease in percentage predicted FVC

Follow-up started at the time of rituximab initiation. The authors report on the cohorts separately because of baseline differences in age, race/ethnicity, comorbidities, prior treatments and clinical manifestations.

Composite Outcome

The respective outcomes for the 36 patients in the MGB cohort and the 14 in the UCM cohort were:

  • Improved—50% in the MGB cohort, and 57% in the UCM cohort
  • Stable—33% and 14%
  • Worsened and died—17% and 21%
  • Lost to follow-up—1 patient in the UCM cohort

Change in Pulmonary Function

PFT data were available for 32 MGB patients and 12 UCM patients:

  • Improved—42% in the MGB cohort, and 58% in the UCM cohort
  • Stable—40% and 42%
  • Worsened and died—9% and 0%
  • Tapered off glucocorticoids completely—39% and 50%


Few adverse events were noted:

  • Minor infusion reactions—0 MGB patients and 2 UCM patients
  • Infections—7 and 2
  • Infections requiring hospitalization—5 and 2
  • Discontinued therapy because of infection—2 and 0

Most patients were receiving concomitant glucocorticoid therapy during some portion of follow-up, so it's impossible to say what proportion of infections resulted from rituximab exposure alone.

Future randomized, controlled trials might be able to determine which clinical, serologic and radiologic factors influence response to rituximab in patients with IPAF.

Learn more about the Division of Rheumatology, Allergy & Immunology

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