Patient background
The characteristics of the patients are shown in Table 1. The characteristics of each patient at the diagnosis of EGPA are shown in Supplementary Table 1. At the time of initiating MPZ therapy, the median age [interquartile range] of the 16 patients with EGPA was 61.5 [53.3−70.5] years, and the disease duration was 54 [22−144] months. Regarding medical history, all patients were treated with CS. The without-MPZ included four patients with relapsing EGPA, 11 with refractory EGPA, and one with remission, while the with-MPZ included 10 patients with relapsing EGPA and six with refractory EGPA. No statistically significant differences were observed in the concomitant CS dose or the rate of concomitant immunosuppressant use between both groups. There were also no statistically significant differences in BVAS, VDI, positivity rate for anti-neutrophil cytoplasmic antibody, eosinophil count, or C-reactive protein level between the two groups.
Effectiveness of MPZ
The remission rates at 1 year (the primary endpoint) were 6.3% at month 1, 12.5% (1/16 patients) at month 3, 6.3% at month 6, and 0% at month 12 in the without-MPZ, thereby showing no statistically significant differences. The corresponding rates in the with-MPZ were 12.5% at month 1, 31.3% at month 3, 50.0% at month 6, and 75.0% at month 12. In this group, the remission rate significantly increased at month 3 onwards (Figure 1A). The remission rate at 1 year was significantly higher in the with-MPZ than in the without-MPZ.
In the without-MPZ, BVASs were 0 [0−2.0] at month 1, 0 [0−2.0] at month 3, 0 [0−2.0] at month 6, and 1.0 [0−3.8] at month 12, showing no significant change from the BVAS at month 0. In the with-MPZ, BVASs were 0 [0−2.8] at month 1, 0 [0−0] at month 3, 0 [0−0] at month 6, and 0 [0−0] at month 12. BVASs at month 1 and afterward significantly decreased from BVAS at month 0 (Figure 1B). The decrease in BVAS during the 1-year period in the with-MPZ was 0.5 [0−3.5], which was significantly larger than −2.0 [−3.0−0] in the without-MPZ (Figure 2A).
Based on the changes in BVASs for each item, respiratory symptoms were exacerbated in the without-MPZ but improved immediately after initiating MPZ therapy. The number of patients with symptoms decreased from 11/16 to 2/16 after 1 year of treatment. Ear, nose, and throat symptoms also improved as the number of patients with symptoms decreased from 3/16 to 6/16 patients at 1 year after initiating MPZ therapy. In contrast, neuropathy did not improve in either the with-MPZ or without-MPZ. In the with-MPZ, no organ dysfunction was exacerbated at month 12 (Table 2).
In the without-MPZ, VDI scores were 3.5 [3.0−4.8] at month 1, 4.0 [3.0−5.5] at month 3, 4.0 [3.0−5.5] at month 6, and 4.0 [3.0−5.5] at month 12, showing no significant increase compared with those at month 0. In the with-MPZ, VDI scores were 4.0 [3.0−5.5] at month 1, 4.0 [3.0−5.5] at month 3, 4.0 [3.0−5.5] at month 6, and 4.0 [3.0−5.5] at month 12, showing no significant changes (Figure 1C). The increase in the VDI score during the 1-year period was 0 [0−0.8] in the without-MPZ and 0 [0−0] in the with-MPZ, showing no significant difference between the two groups (Figure 2B).
In the without-MPZ, eosinophil counts were 280.4 [63.2−426.8]/μL at month 1, 217.8 [93.3−1354.2]/μL at month 3, and 293.9 [39.1−880.7]/μL at month 6, showing no significant changes compared with those at month 0. In the with-MPZ, eosinophil counts were 54.8 [10.6−99.8]/μL at month 1, 25.2 [12.8−53.9]/μL at month 3, 29.4 [9.63−42.5]/μL at month 6, and 28.8 [20.5−68.0] at month 12, showing significant reduction at month 1 onwards (Figure 1D). The reduction in the eosinophil count during the 1-year period in the with-MPZ was 146.2 [9.88−2449.9], which was significantly higher than −8.8 [−2927.4−175.4] in the without-MPZ (Figure 2C).
In the without-MPZ, concomitant CS doses were 8.0 [5.0−10.0] mg/day at month 1, 7.0 [3.5−10.0] mg/day at month 3, 6.5 [2.6−10.0] mg/day at month 6, and 6.0 [2.6−10.0] mg/day at month 12, showing no significant changes compared with those at month 0. In the with-MPZ, concomitant CS doses were 6.5 [2.6−10.0] mg/day at month 1, 5.0 [2.3−7.4] mg/day at month 3, 4.5 [0.5−5.0] mg/day at month 6, and 2.5 [0.1−3.8] mg/day at month 12, showing significant reduction at month 3 onwards (Figure 1E). When cumulative concomitant CS doses were compared between the with-MPZ and without-MPZs, the doses were 2665 [1473.8−3993.8] mg/year in the without-MPZ and 1655 [570.0−2190.0] mg/year in the with-MPZ. The cumulative concomitant CS doses significantly decreased in the with-MPZ (Figure 2D). The changes in the use of immunosuppressant(s) are shown in Table 3. The number of patients with concomitant immunosuppressant(s) use reduced from 10 to nine patients at 1 year in the without-MPZ and from nine to five patients in the with-MPZ.
MPZ retention rate and safety
The 1-year MPZ retention rate was 100%. Although three patients had an infection, all patients continued MPZ. Adverse events before and after initiating MPZ therapy are shown in Table 4. All three patients who had an infection after initiating MPZ therapy had the same infection within 1 year before initiating MPZ therapy. No patients had a new infection after initiating therapy.