BIOLOGIC THERAPY IN ANCA-ASSOCIATED VASCULITIS: NEW PERSPECTIVES

U. SpecksMayo Clinic, Rochester, MN, United StatesThis lecture reviews the medical management of diffuse alveolar hemorrhage (DAH) in light of the results of randomized controlled trials and recent cohort studies with particular emphasis on the efficacy of rituximab as primary remission induction agent and the role of plasma exchange (PLEX) as an adjunct. Diffuse alveolar hemorrhage is a disease manifestation affecting up to 25% of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). It frequently leads to respiratory failure and reported mortality is high. Early recognition and implementation of definitive remission induction therapy is essential to control this severe disease manifestation and assure a good outcome. Conventional therapy consisted of combination of glucocorticoids with cyclophosphamide (CYC). Patients with respiratory failure due to DAH are thought to benefit from PLEX, but the literature is not clear on this, and PLEX is the subject of an ongoing multicenter randomized controlled trial. A quarter of the participants of a large randomized, double-masked, double dummy-controlled trial comparing RTX to CYC for remission induction in severe GPA and MPA (RAVE) had documented DAH at the time of enrollment. The trial showed that RTX is not inferior to CYC. This finding was consistent across all primary and secondary endpoints and outcome measures as well as patient subset analyses including those with major renal disease and DAH. For patients who entered the trial with a disease relapse, and those who were PR3-ANCA positive, RTX was shown to be superior. However, as patients requiring mechanical ventilation for respiratory failure caused by DAH were excluded from the RAVE trial, the efficacy of RTX in that subset of patients with GPA and MPA deserves further study. In a recent analysis of 73 consecutive patients with DAH caused by GPA or MPA a SpO2/FiO2 ratio of <450, neutrophilic alveolitis determined by bronchoalveolar lavage (>30% neutrophils on cell differential), and a serum C-reactive protein level >25 mg/dL were identified by multivariate analysis as predictors of respiratory failure. There was no difference in hospital mortality, hospital length of stay, ICU length of stay, or days on mechanical ventilation between patients who received CYC (n=31) compared to those who receive RTX (n=37) as sole remission induction agent in addition to glucocorticoids. However, 89% of RTX-treated patients were in complete remission at 6 months, compared to 68% of CYC-treated patients (p=0.02). 32 of the 73 patients with DAH received PLEX as adjunct to remission induction therapy. Patients who received PLEX had more severe vasculitis activity and worse respiratory failure than patients who did not. However, even after adjusting for the probability of receiving PLEX based on more severe disease, there was no difference in any of the outcomes measures between patients who received PLEX versus those who did not. Similarly, among an aggregate of patients with DAH due to GPA and MPA combined from 11 studies from 1985 and 2015, there is no difference in resolution of DAH and hospital mortality associated with the use of PLEX. In conclusion, RTX is an effective remission induction agent in patients with DAH caused by GPA or MPA, regardless of the severity of DAH. The addition of PLEX to standard remission induction therapy is not clearly supported by currently available data and the outcome of a large multicenter randomized controlled trial of this treatment modality is eagerly awaited. Disclosure of Interest: U. Specks Consultant for: Genentech DOI: 10.1136/annrheumdis-2015-eular.6807Citation: Annals of the Rheumatic Diseases, volume 74, supplement 2, year 2015, page 3Session: Difficult vasculitis (Speaker Presentations )