Azathioprine (AZA) and mycophenolate mofetil (MMF) are first-line steroid-sparing agents used in combination with a corticosteroid for the treatment of pemphigus, but few direct comparisons between these two treatment modalities have been made. |
Reliable data on whether AZA or MMF differ in efficacy may be valuable, especially in financially restrained countries where anti-CD20 antibodies are not readily available or affordable. |
Corticosteroid in combination with either AZA or MMF is an effective treatment regimen for pemphigus, with similarly high rates of patients on AZA or MMF as adjuvant achieving remission. |
Compared to AZA, MMF demonstrates a shorter time to achieve complete remission in patients with pemphigus on therapy and a significantly higher steroid-sparing effect. |
Introduction
Methods
Assessments of Treatment Response
Other Outcome Assessments
Statistical Analysis
Results
Characteristics | AZA group (n = 37) | MMF group (n = 25) | p value |
---|---|---|---|
Sex (male/female), n | 16/21 | 7/18 | 0.223 |
Diagnosis (PV/PF), n | 29/8 | 15/10 | 0.118 |
Extent of involvement (mucosal only/cutaneous only/mucocutaneous), n | 6/8/23 | 4/12/9 | 0.074 |
Patient category (new/old/relapse), n | 23/9/5 | 12/11/2 | 0.256 |
Age at onset (years), mean (SD) | 44.54 (13.68) | 55.13 (17.36) | 0.062 |
Age at diagnosis (years), mean (SD) | 44.92 (13.78) | 52.29 (17.30) | 0.070 |
Age at start adjuvant (years), mean (SD) | 46.27 (13.71) | 52.4 (17.22) | 0.125 |
Disease duration (months), median (range) | 10 (0.5180) | 6 (0.5,96) | 0.959 |
Follow-up duration (days), median (range) | 595 (7,2363) | 399 (13,1834) | 0.199 |
Baseline ABSIS, median (range) | 4.5 (0.25,43.75) | 4 (1.125,41) | 0.293 |
Baseline anti-Dsg-1 (≤ 20/21–100/101–200/> 200 U/mL), n | 1/6/7/15 | 2/5/3/14 | 0.677 |
Baseline anti-Dsg-3 (≤ 20/21–100/101–200/> 200 U/mL), n | 5/3/5/16 | 8/4/6/5 | 0.101 |
Baseline prednisolone (mg/kg), mean (SD) | 0.53 (0.24) | 0.48 (0.21) | 0.479 |
Outcomes | AZA (n = 37) | MMF (n = 25) | p value |
---|---|---|---|
No. of patients reaching ECP | |||
PV + PF | 30/34 (88.24%) | 15/21 (71.43%) | 0.156 |
PV | 23/27 (85.19%) | 8/12 (66.67%) | 0.221 |
PF | 7/7 (100%) | 7/9 (77.78%) | 0.475 |
No. of patients achieving CR on therapy | |||
PV + PF | 27/37 (72.97%) | 18/25 (72%) | 0.933 |
PV | 22/29 (75.86%) | 11/15 (73.33%) | 1.00 |
PF | 5/8 (62.50%) | 7/10 (70%) | 1.00 |
No. of patients achieving CR off therapy | |||
PV + PF | 9/37 (24.32%) | 5/25 (20%) | 0.69 |
PV | 7/29 (24.14%) | 3/15 (20%) | 1.00 |
PF | 2/8 (25%) | 2/10 (20%) | 1.00 |
No. of patients achieving immunological remission | |||
PV + PF | 13/36 (36.11%) | 9/24 (37.50%) | 0.913 |
PV | 12/28 (42.86%) | 5/14 (35.71%) | 0.657 |
PF | 1/8 (12.50%) | 4/10 (40%) | 0.314 |
Median time (months) to reach ECP (95% CI) | |||
PV + PF | 2.9 (2.1, 4.4) | 3.5 (1.6, 5.9) | 0.362 |
PV | 3.7 (2.1, 4.6) | 4.1 (1.8, –) | 0.319 |
PF | 1.8 (0.6, 2.9) | 1.6 (1.4, –) | 0.329 |
Median time (months) to achieve CR on therapy ( 95% CI) | |||
PV + PF | 12.5 (8.7, 17.4) | 7.3 (5.2, 12.3) | 0.019* |
PV | 14.4 (8.9, 18.2) | 6.5 (3.8, 15.7) | 0.093 |
PF | 8.3 (3.5, –) | 8.6 (3.4, 10.9) | 0.329 |
Median time (months) to achieve CR off therapy (95% CI) | |||
PV + PF | 52.3 (49.7,60.5) | 29.5 (17.8, –) | 0.11 |
PV | 52.2 (49.7, –) | 29.5 (18, –) | 0.370 |
PF | 55.0 (33.4, –) | 17.8 (14.4, –) | 0.128 |
Median time (months) to achieve immunological remission (95% CI) | |||
PV + PF | 41.9 (15.0, –) | 15.3 (5.38, –) | 0.157 |
PV | 41.4 (13.3, –) | 15.6 (11.7, –) | 0.527 |
PF | – (4.2, –) | 5.4 (4.9, –) | 0.255 |
Cumulative steroid level at ECP (mg), median (range) | |||
PV + PF | 2730 (360, 20,175) | 1480 (700, 12,127.5) | 0.63 |
PV | 2905 (420, 20,175) | 2022.5 (840, 12,127.5) | 0.588 |
PF | 1680 (360, 4550) | 1330 (700, 5985) | 0.749 |
Cumulative steroid level at CR on therapy (mg), median (range) | |||
PV + PF | 7740 (610, 42,990) | 3473.8 (397.5, 12,367.5) | 0.007* |
PV | 8583.75 (610,42,990) | 3252.5 (397.5, 12,367.5) | 0.012* |
PF | 4080 (1342.5, 12670) | 4117.5 (1262.5, 9010) | 0.569 |
Cumulative steroid level at CR off therapy (mg), mean (SD) | |||
PV + PF | 12,857.3 (4491.71) | 7590.5 (3428.34) | 0.043* |
PV | 11621.11 (4065.65) | 8380.83 (3937.04) | 0.278 |
PF | 17,185 (3751.20) | 6405 (3365.82) | 0.094 |
Characteristic | Crude HR (95% CI) for CR when on therapy | p value | Adjusted HRa (95% CI) for CR when on therapy | p value |
---|---|---|---|---|
Treatment | ||||
MMF | 2.07 (1.11–3.86) | 0.021 | 2.55 (1.15–5.63) | 0.021 |
AZA | 1 | 1 |
Steroid-Sparing Effect, Pemphigus Recurrence and Adverse Events
Adverse events | AZA (n = 37) | MMF (n = 25) | p value |
---|---|---|---|
Oral candidiasis | 7 (18.92%) | 2 (8%) | 0.29 |
Dermatophyte infection | 2 (5.41%) | 0(0%) | 1 |
Cellulitis | 2 (5.41%) | 3 (12%) | 0.39 |
Pneumonia | 1 (2.7%) | 1 (4%) | 1 |
Hyperglycemia | 6 (4.2%) | 1 (4%) | 0.23 |
Fever | 5 (2.41%) | 0 (0%) | 0.51 |
Abdominal discomfort | 1 (2.7%) | 0 (0%) | 1 |
Hepatitis | 4 (10.81%) | 1 (4%) | 0.64 |
Meningitis | 1 (2.7%) | 0 (0%) | 1 |
TB infection | 1 (2.7%) | 0 (0%) | 1 |
Nausea/vomiting | 1 (2.7%) | 0 (0%) | 1 |
Diarrhea | 0 (0%) | 1 (4%) | 0.16 |
Herpes zoster | 2 (5.41%) | 2 (8%) | 1 |
URI | 0 (0%) | 2 (8%) | 0.16 |
Mild transaminitis | 2 (5.41%) | 0 (0%) | 0.51 |
Bone marrow suppression | 2 (5.41%) | 0 (0%) | 1 |
Eczema herpeticum | 0 (0%) | 1 (4%) | 0.4 |
Adverse events leading to drug withdrawal | 8 (21.6%): hepatitis (4), meningitis (1), TB infection (1), BM suppression (2) | 3 (12%): hepatitis (1), pneumonia (1), cellulitis followed by DVT (1) | 0.33 |