Background/Purpose: ENT involvement is the most prevalent manifestation of GPA.  Rituximab (RTX) is a proven effective remission induction therapy for

severe GPA with vasculitic manifestations.  The efficacy of RTX for the granulomatous manifestations of GPA is debated.  No previous studies have looked at the efficacy of RTX specifically for ENT manifestations of GPA.  The aim of this study was to compare the efficacy of RTX to other therapies for the ENT manifestations of GPA, in a well-characterized cohort.

Methods: Subjects with GPA seen at a tertiary care ENT practice between 2003 and 2013 were identified via ICD-9 code.  Charts were reviewed for demographics, organ involvement, ENT disease activity, medications, and procedures at each visit.  At each visit subjects had complete ENT exam including endoscopic visualization of the upper airway and audiometry, for those with otologic involvement. Endoscopic exam and assessment of ENT disease activity were all performed by one otolaryngologist with specific expertise in GPA.  Primary outcome was ENT disease activity at each visit in subjects on RTX versus those on all other therapy.  RTX use was defined a priori as most recent infusion within 6 months or continued B cell depletion at the time of the visit. Secondary outcomes were comparison of ENT disease activity in subjects on RTX to those on MTX, AZA, CYC or TMP-SMX. 

Results:

99 subjects with GPA were identified and 975 office visits from the subjects were analyzed.  The mean age was 49.8 years, mean disease duration 8.1 years, 68.7% were female, 63.5% had limited disease and 76.8% had positive PR3.  48 subjects never received RTX and 51 received RTX at least once.  Comparing patients who ever received RTX to those who did not, those treated with RTX were significantly more likely to have severe disease (48% vs 26%, p=0.027) and were also more likely to have ENT damage at baseline (94% vs73%, p=0.004).  There were no other differences between the groups. 

Outcomes: There was no active ENT disease at 92.4% of visits for subjects on RTX compared to 53.7% of visits for subjects not receiving RTX (OR 11.0; 95%CI 5.5-22.0, p<0.0001).  Adjusting for ENT damage, extent and duration of disease, age, and sex, RTX was still favored (OR 12.0; 95%CI 5.9-24.3, p<0.0001).  Subjects on RTX compared to MTX, AZA, CYC, or TMP-SMX were significantly more likely to be in ENT remission, p<.0001 for each comparison. (Table1)

Conclusion: RTX is an effective treatment for ENT manifestations of GPA. Subjects treated with RTX were  >11 times less likely to have active ENT disease compared to those not on RTX.   Those treated with RTX were far less likely to have active ENT disease than those treated with other immunosuppressives. This represents the largest cohort of patients in whom meticulously assessed ENT outcomes with RTX versus other therapies is described and suggests RTX is superior to conventional immunosuppressives for ENT manifestations of GPA.