238. EFFICACY OF CONVENTIONAL IMMUNOSUPPRESSANTS IN STEROID-DEPENDENT OR REFRACTORY EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS: STUDY ON A NEW CANADIAN PATIENT COHORT
Bibliographic record
Abstract
Background: Mepolizumab and rituximab have been shown to be effective in relapsing, refractory and/or steroid-dependent eosinophilic granulomatosis with polyangiitis (EGPA), though limited data exists for conventional immunosuppressants. We aimed to describe a new cohort of adults with EGPA and report on the disease control efficacy of conventional immunosuppressants. Methods: A retrospective analysis of an EGPA cohort from Toronto was conducted. Five-year relapse-free survival analyses were computed comparing ANCA status, sex and year of diagnosis. Patients with relapsing, refractory and/or steroid-dependent EGPA with similar entry criteria as the main mepolizumab trial or rituximab cohort, who were started on conventional immunosuppressant’s, were assessed for remission at 24- and 52-weeks after treatment initiation. Remission was defined as a Birmingham Vasculitis Activity Score of 0 and a prednisone dose of 4 mg, ⩽7.5 mg or any prednisone dose per day (defined as MEPO4, MEPO7.5 or RITUX, corresponding to the mepolizumab or rituximab study endpoints, respectively). Results: In this cohort of 110 patients with EGPA, 1, 2, and ⩾3 relapses occurred in 38 (34.6%), 10 (9.1%), and 4 patients (3.6%), respectively. Five-year relapse-free survival rates were 40.9% (95% CI 0.490-0.698) for all patients; 40% (95% CI 0.371-0.683) for ANCA-positive and 39.2% (95% CI 0.463-0.750) for ANCA-negative patients (p = 0.683); 53.7% (95% CI 0.549-0.820) for females and 30.4% (95% CI 0.327-0.632) for males (p = 0.030); 64.3% (95% CI 0.543-0.803) for those diagnosed in 2010, and 40.7% (95% CI 0.298-0.635) for those diagnosed >2010 (p = 0.013). Twenty-four patients met eligibility criteria of relapsing, refractory and/or steroid-dependent EGPA and used methotrexate (n = 15), azathioprine (n = 8), or leflunomide (n = 1). Remission rates achieved at 24-weeks in our study [vs the corresponding mepolizumab or rituximab trial rates] were 8.3% for MEPO4 [vs. 28.0%]; 41.6% in MEPO7.5 [vs. 45%] and 62.5% for RITUX [vs. 34%]; remission at 52-weeks was 16.7% for MEPO4 [vs. 19%], 45.8% for MEPO7.5 [vs. 24%] and 50.0% for RITUX [vs. 49%]. Conclusion: Though retrospective biases must be acknowledged, the rates of remission observed in our study using conventional immunosuppressant’s were substantial and should be kept in mind when interpreting results of recent and future studies on biologics in EGPA. Disclosures: CP reports receiving fees for serving on advisory boards from Chemocentryx, GlaxoSmithKline, Sanofi and Hoffman-LaRoche; he also reports lecture fees and research grant support from Hoffman-La Roche.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".