Extended Follow-Up Of a Investigator-Initiated trial Comparing Two Sequential Induction and Maintenance Treatment Regimens For Proliferative Lupus Nephritis Based Either On Cyclophosphamide Or Cyclosporine A

Jakub Zavada¹, Satu Pesickova², Romana Rysava³, Pavel Horak⁴, Zbynek Hrncir⁵, Jozef Rovensky⁶, Jozef Lukac⁷, Jirina Vitova⁸, Jana Böhmova⁹, Marta Olejarova¹⁰, Dana Tegzova¹¹ and Vladimir Tesar¹², ¹Charles University, Prague, Czech Republic, ²Nephrology, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic, ³General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic, ⁴3rd Department of Internal Medicine, 3rd Department of Internal Medicine University Hospital Olomouc, Olomouc, Czech Republic, ⁵2nd Department of Medicine, Faculty of Medicine and University Hospital, Hradec Kralove, Czech Republic, ⁶PRINTO, Genoa, Italy, ⁷National Institute of Rheumatology, Piestany, Slovakia, ⁸Hospital, Ceske Budejovice, Czech Republic, ⁹Faculty Hospital St. Anna, Brno, Czech Republic, ¹⁰Institute of Rheumatology, Prague, Prague, Czech Republic, ¹¹Institute of Rheumatology, Prague, Czech Republic, ¹²Department of Nephrology, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: cyclophosphamide, cyclosporine and lupus nephritis

Session Information

Title: Systemic Lupus Erythematosus - Clinical Aspects I - Renal, Malignancy, Cardiovascular Disease

Session Type: Abstract Submissions (ACR)

Background/Purpose:

In the investigator-initiated CYLOFA-LUNE trial we tested the hypothesis that immunosuppressive regimen based on Cyclosporine A (CYA) may have similar efficacy but greater safety than that based on cyclophosphamide (CPH).

CYCLOFA-LUNE TRIAL

a multicenter, randomized, open-label, controlled trial

conducted from January 2002 through December 2006 in 7 centers in Czech Republic and one center in Slovakia

Eligibility criteria:

•The diagnosis of systemic lupus erythematosus (by meeting 4 criteria of the American College of Rheumatology)

•Renal biopsy documenting proliferative glomerulonephritis class III or IV according to WHO/ISN-RPS

•Clinical activity as defined by presence of at least two of the following: abnormal proteinuria (> 500mg /24-hours), active urinary sediment, and/or C3 hypocomplementemia

Treatment:

The duration of the controlled study protocol was 18 months

Cyclophosphamide (CPH) arm: 8 boluses of intravenous cyclophosphamide (10mg/kg) given within 9 months in subsequently prolonged intervals (2x3weeks, 4×4 weeks, 2×6 weeks) followed by 4-5 oral cyclophosphamide boluses (10mg/d in 6-8 week intervals).

Cyclosporine arm: oral cyclosporine A (CyA) 4-5mg/kg/day (given in two divided doses) for 9 months followed by gradually decreasing dose of cyclosporine (3.75-1.25 mg/kg/day) within the next 9 months

Glucocorticoids: prescribed according to a unified protocol

The main purpose of the current analysis was to ascertain the long-term renal outcome of patients randomised in the CYCLOFA-LUNE trial.

Methods:

Data for kidney function, and adverse events (death, cardiovascular event, tumor, premature menopause) were collected by a cross-sectional suvey for 38 of 40 patients initially randomised in the CYCLOFA-LUNE trial

Results:

The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents, and blood pressure lowering drugs.

	All (n=38)	CPH (n=19)	CyA (n=19)
Age (years), mean (SD)	39 (10)	37 (5)	38 (8)
Female, n	27 (71)	13 (68)	14 (74)
Follow-up (years), median (range)	7.7 (5.0-10.3)	7.4 (5.0-9.7)	8.3 (5.3-10.3)
50% increase in creatinine concentration	5 (13)	3 (16)	2 (11)
Non-sustained doubling of the creatinine concentration	2 (5)	1 (5)	1 (5)
Sustained doubling of serum creatinine	2 (5)	1 (5)	1 (5)
End-stage renal disease	2 (5)	1 (5)	1 (5)
Current serum creatinine (μmol/l)	67 (19)	71 (23)	63 (15)
Current 24 h proteinuria (g)	0.4 (0.6)	0.5 (0.5)	0.4 (0.7)
Additional IS drugs ever received	1 (1)	1 (2)	1 (1)
Deaths	0 (0)	0 (0)	0 (0)
Malignancy	2 (5)	0 (0)	2 (11)
Cumulative cardiovascular events	1 (3)	1 (5)	0 (0)
Premature menopause*	1 (4)	1 (8)	0 (0)
Pregnant*	9 (33)	6 (46)	3 (21)
Current SLICC DI (median, IQR)	0.0 (1.0)	0.0 (1.0)	0.5 (1.0)

2 patients included in the ESRD group are counted within the other groups with less severe renal impairment), Figures are numbers (%) of patients, or median (IQR) * since the end of the CYCLOFA-LUNE protocol treatment.

Conclusion:

Both regimens based either on CPH or CyA achieved good and similar clinical results in the very long term

Acknowledgements: Supported by the project (Ministry of Health, Czech Republic) MZO 00023728.

Disclosure:

J. Zavada,
None;

S. Pesickova,
None;

R. Rysava,
None;

P. Horak,
None;

Z. Hrncir,
None;

J. Rovensky,
None;

J. Lukac,
None;

J. Vitova,
None;

J. Böhmova,
None;

M. Olejarova,
None;

D. Tegzova,
None;

V. Tesar,
None.

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