Efficacy of Lower Dose Prednisolone in the Induction of Remission of Lupus Nephritis

• Status: Completed
• Trial end date: 2019-09-30
• Target enrollment: 0
• Participant gender: All

Summary

The LN is a common cause of mortality and morbidity in SLE. The use of high-dose glucocorticoids (GC) with an immunosuppressive agent is usual practice for treating this condition. Higher dose of GC use might cause adverse effects along with clinical improvement. Studies had reported comparable outcome of lower dose of GC with minimum side effects. The aim of this study was to determine the outcome of lower dose prednisolone in the induction of remission of proliferative LN.

This prospective, clinical trial was conducted in Rheumatology outpatient and inpatient department of BSMMU from July 2018 to September 2019. Thirty-two subjects were enrolled after having informed consent. The ACR (American College of Rheumatology) criteria was followed for diagnosis of SLE. The patients of both genders, age ≥18 years, who fulfilled the ACR criteria of LN and unable to afford MMF were enrolled.

The patient evaluation tool was SELENA-DAI and Bengali version of SF-12 questionnaire. The 24-hour urinary protein, urine R/M/E, serum creatinine, CBC, serum C3, C4 levels and anti-dsDNA were done at baseline and at final visit of the study.

All patients received pulse I/V methylprednisolone 500 mg/day daily for 3 doses. After then experimental group received oral prednisolone 0.5 mg/kg/day and control group received oral prednisolone 1 mg/kg/day for a period of 4 weeks. After then the prednisolone was tapered by 10 mg/day in every two weeks until 40 mg/day, then 5 mg/day in every two weeks until 10 mg/day is reached, after two weeks the dose was tapered by 2.5 mg/day to a maintenance dose of 7.5 mg/day. Both groups were treated in the background of hydroxychloroquine (HCQ), angiotensin receptor blocker (ARB) and pulse I/V cyclophosphamide (CYC) for 6 cycle.

The ethical clearance was obtained from Institutional Review Board (IRB) of BSMMU and technical clearance was taken from rheumatology technical board.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
• Treatments: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Criteria

Inclusion Criteria:

1. Age ≥18 years of both sexes

2. Diagnosed case of systemic lupus erythematosus (SLE) as per ACR criteria

3. Patients consenting to participate in the study

4. Class III/IV lupus nephritis (LN) as evidenced by:

• Confirmed proteinuria ≥ 500 mg/24 hours when assessed by 24-hour urine collection And

• High titer anti-dsDNA (>75 U/ml) and low C3 (<0.9 g/l) and/or C4 (<0.1 g/l) Or

• Kidney biopsy: with a histologic diagnosis of class III or IV lupus nephritis (International Society of Nephrology/Renal Pathology Society 2003 classification of lupus nephritis)

Exclusion Criteria:

1. Subjects not giving written informed consent

2. Pregnant or lactating women

3. Patient willing to be treated with MMF rather than CYC

4. Had taken CYC within 4 weeks prior to screening

5. Had taken >15 mg/day of prednisolone (or equivalent) for a period of >10 days during the previous month

6. Renal thrombotic microangiopathy

7. Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation of ≤45 mL/min/1.73 m2 at screening

8. Dialysis dependent patients, currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period

9. A previous kidney transplant or planned transplant within study treatment period

10. Altered liver function (alanine aminotransferase greater than 2.5 times the upper limit of normal) at screening and confirmed before randomization

11. Malignancy

12. Lymphoproliferative disease or previous total lymphoid irradiation

13. Active bleeding disorders

14. Active tuberculosis (TB)

15. Diabetes mellitus

16. Any known hypersensitivity or contraindication to CYC, corticosteroids or any components of these drug products

17. Any overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes (e.g., scleroderma with significant pulmonary hypertension; any condition for which additional immunosuppression is indicated)