Glucocorticoid withdrawal in an incident cohort of lupus nephritis patients

Séverine Wautier, Farah Tamirou, Séverine Nieuwland-Husson, Frédéric Houssiau Published in the journal : November 2018 Category : Mémoires de Recherche Clinique

Summary :


Nephritis is one the most frequent and severe manifestation of systemic lupus erythematosus. Treatment of lupus nephritis (LN) is based on the use of glucocorticoids (GC) and other immunosuppressants on the one hand, and on optimal renal protection on the other hand. The objective is to induce renal remission while avoiding cumulative damages. In this respect, chronic GC use is associated with many severe adverse events leading to increased morbidity. A prompt stop and withdrawal of GC is therefore of paramount importance.



Our retrospective study was aimed at defining the determinants of GC withdrawal in patients with incident LN and at assessing the corresponding benefits and risks.



We studied 90 cases of incident biopsy-proven LN from the LOUvain LUpus Nephritis Inception Cohort (LOULUNIC) that were followed in our center. We then determined the number of patients who were able to withdraw GC, either permanently or transiently. Next, we compared the groups at baseline and during follow-up. Clinical, pathological, and biological data were extracted from our database. The SLICC/ACR-DI was assessed upon last visit. We used the Lupus-QOL questionnaire to assess patients’ quality of life. Unpaired t-test, Mann-Whitney tests, and ANOVA were performed, as appropriate. RESULTS Among the 90 patients with incident LN, 43 (48%) could stop GC (E group), of whom 32 permanently (P group) and 11 transiently (T group). Median time to GC stop was 37 months. The remaining 47 patients (52%) never stopped GC (N group). At baseline, serum creatinine, uP/C ratio, ISN/RPS classes, activity, and chronicity indices did not differ between groups, nor did the mean initial dose of methylprednisolone (MP) (N: 28 mg/dl; E: 32 mg/dl; P: 31 mg/dl), and the use of IV MP pulses (82 and 77% in N and E groups, respectively) and IV cyclophosphamide (81 and 77%, respectively). During the first year, the mean (SD) uP/C decreased significantly more in the E group than in the N group (p=0.028 by ANOVA), with striking differences at 3 months (N: 1.73 ± 1.87; E: 0.96 ± 1.34; p=0.038 by unpaired t-test). A similar difference at 3 months was noticed in group P patients (0.85 ± 0.76; p=0.02 by unpaired t-test). Interestingly, the mean MP dose at 3 months was significantly higher in the E (19 ± 8) and P (20 ± 9) groups than in the N group (15 ± 6) (p=0.005 by unpaired t-test). At last follow-up, serum creatinine was significantly lower in patients from E and P groups compared to those from the N group. Eight of the 11 patients from the T group suffered from a renal relapse justifying GC resumption after a median duration of 30 months. Of note is that the SLICC/ACR-DI was significantly lower in patients from E and P groups than in those from the N group (p=0.0068 and 0.0027, respectively). Patients from P and T groups had a significantly better quality of life than patients from the N group (P: 86%; T: 71%; N: 68%).



We showed that i) half of LN patients were able to withdraw GC (one third permanently); ii) patients who achieved GC withdrawal accumulated less damages and enjoyed a better quality of life; iii) proteinuria of patients who stopped GC decreased much more promptly over time, including in the first year; iv): patients who stopped GC had received higher doses during the first 3 months of treatment, thus suggesting that higher GC doses during the first 3 months are associated with a higher probability of withdrawal.