Table 1.
Characteristics/measures of 70 AAV patients at first rituximab infusion.
| Characteristics or measures | Discovery cohort (N = 35) | Validation cohort (N = 35) | Total cohort (N = 70) |
|---|---|---|---|
| Age [mean (SD) years] | 51 (16.9) | 53 (20.2) | 52 (18.5) |
| Male [N (%)] | 19 (54.3) | 19 (54.3) | 38 (54.3) |
| Ethnicity [N (%)] | |||
| Caucasian | 28 (80.0) | 33 (94.3) | 61 (87.1) |
| South Asian | 5 (14.2) | 2 (5.7) | 7 (10.1) |
| Chinese/South East Asian | 1 (2.9) | 0 | 1 (1.4) |
| Mixed race | 1 (2.9) | 0 | 1 (1.4) |
| Disease duration [median (IQR) years] | 2.2 (0.9–5.3) | 1.9 (0.4–3.5) | 2 (0.6–4.4) |
| Disease type [N (%)] | |||
| Granulomatosis with polyangiitis (GPA) | 29 (82.9) | 22 (62.9) | 51 (72.9) |
| Microscopic polyangiitis (MPA) | 6 (17.1) | 10 (28.6) | 16 (22.9) |
| Eosinophilic granulomatosis with polyangiitis (EGPA) | 0 | 3 (8.6) | 3 (4.3) |
| Positive ANCA at diagnosis [No. (%)] | 34 (97.1) | 30 (85.7) | 64 (91.4) |
| Anti-PR3 antibody | 25 (71.4) | 19 (54.3) | 44 (62.9) |
| Anti-MPO antibody | 5 (14.3) | 10 (28.6) | 15 (21.4) |
| Immunofluoresence only | 4 (11.4) | 1 (2.9) | 5 (7.1) |
| Negative but with a positive histology of GPA/EGPA | 1 (2.9) | 5 (14.3) | 6 (8.6) |
| Positive anti-PR3/anti-MPO at cycle 1 rituximab infusion [N (%)] | 26 (74.3) | 25 (71.4) | 51 (72.9) |
| Prior/concomitant therapy with cyclophosphamide [N (%)] | 32 (91.4) | 30 (85.7) | 62 (88.6) |
| No. of prior immunosuppressant failure (including Cyclophosphamide and plasma exchange but excluding steroid) [median (range)] | 2 (0–5) | 2 (0–4) | 2 (0–5) |
| Concomitant immunosuppressant/started within 3 months of cycle 1 rituximab infusion [N (%)] | 23 (65.7) | 23 (65.7) | 46 (65.7) |
| Methotrexate | 6 (17.1) | 4 (11.4) | 10 (14.3) |
| Azathioprine | 8 (22.9) | 11 (31.4) | 19 (27.1) |
| Mycophenolate mofetil | 9 (25.7) | 6 (17.1) | 15 (21.4) |
| Cyclophosphamide a | 2 (5.7) | 3 (8.6) | 5 (7.1) |
| Tacrolimus | 0 | 1 (2.9) | 1 (1.4) |
| Concomitant oral prednisolone [N (%)] | 30 (85.7) | 32 (91.4) | 62 (88.6) |
| Oral prednisolone dose [mean (SD), mg/day] | 13 (9.6) | 23 (13.3) | 18 (12.6) |
| Organ system involvement [N (%)] | |||
| Ear, nose, and throat (ENT) | 25 (71.4) | 23 (65.7) | 48 (68.6) |
| Musculoskeletal and general | 20 (57.1) | 22 (62.9) | 21 (58.3) |
| Chest | 16 (45.7) | 17 (48.6) | 33 (47.1) |
| Renal | 12 (34.3) | 13 (37.1) | 25 (35.7) |
| Mucocutaneous | 8 (22.9) | 6 (17.1) | 14 (20) |
| Nervous system | 3 (8.6) | 6 (17.1) | 9 (12.9) |
| Eyes | 6 (17.1) | 3 (8.6) | 9 (12.9) |
| Abdominal | 1 (2.9) | 1 (2.9) | 2 (2.9) |
| BVAS 3.0 score [mean (SD)] | 10.5 (5.9) | 11.5 (5.5) | 11 (5.7) |
| VDI score (median (range)] | 0 (0–5) | 1 (0–5) | 1 (0–5) |
| Immunoglobulin level [mean (SD), g/dl] | |||
| IgM (normal range, 0.5–2.0 g/L) | 0.95 (0.67) | 0.91 (0.85) | 0.93 (0.76) |
| IgA (normal range, 0.8–4.0 g/L) | 2.22 (1.35) | 1.73 (0.79) | 1.97 (1.13) |
| IgG (normal range, 6.0–16.0 g/L) | 10.03 (4.92) | 8.86 (3.86) | 9.44 (4.43) |
| Lymphocyte count [mean (SD), ×109/L] (normal range 1.00–4.50) | 1.35 (0.65) | 1.10 (0.63) | 1.2 (0.6) |
| Total B cells [median (IQR), ×109 cells/L] | 0.0402 (0.0181–0.0835) | 0.0512 (0.0144–0.1741) | 0.0410 (0.0160–0.1200) |
| Naïve B cells [median (IQR), ×109 cells/L] | 0.0259 (0.0086–0.0540) | 0.0275 (0.0060–0.1021) | 0.0259 (0.0075–0.0782) |
| Memory B cells [median (IQR), ×109 cells/L] | 0.0148 (0.0057–0.0331) | 0.0129 (0.0045–0.0358) | 0.0132 (0.0055–0.0344) |
| Plasmablasts [median (IQR), ×109 cells/L] | 0.0021 (0.0011–0.0032) | 0.0014 (0–0.0033) | 0.0018 (0.0007–0.0032) |
| CRP [mean (SD), mg/L] | 29.1 (37.4) | 27.1 (37.5) | 28.1 (37.2) |
| Total B-cell counts [median (interquartile range), ×109 cells/L] | |||
| Group 1: Patients without concomitant oral immunosuppressant | 0.0519 (0.0713) | 0.0584 (0.2244) | 0.0551 (0.1115) |
| Group 2: Patients with concomitant oral immunosuppressant | 0.0370 (0.0641) | 0.0362 (0.1582) | 0.0369 (0.0789) |
| Difference between groups | p = 0.899 | p = 0.232 | p = 0.509 |
| Total B-cell counts [median (interquartile range), ×109 cells/L] | |||
| Group 1: Patients without concomitant oral prednisolone | 0.0445 (0.0399) | 0.1708 (0.1923) | 0.0583 (0.1338) |
| Group 2: Patients with concomitant oral prednisolone | 0.0402 (0.0804) | 0.0362 (0.1511) | 0.0399 (0.1070) |
| Difference between groups | p = 0.659 | p = 0.226 | p = 0.171 |
BVAS, Birmingham Vasculitis Activity Score version 3.0; IS, immunosuppressant; rituximab, rituximab; VDI, Vasculitis Damage Index.
a
Combination of rituximab and 2–4 pulses of intravenous cyclophosphamide were administered for remission induction of severe AAV to 5 patients with critical subglottic stenosis (N = 3), renal involvement with rapidly rising serum creatinine (N = 1), and probable cardiac involvement (N = 1).