Sequential Therapy for Diffuse Proliferative and Membranous Lupus Nephritis: Cyclophosphamide and Prednisolone Followed by Azathioprine and Prednisolone

Chan, Tak‐Mao; Li, Fu-Keung; Wong, Rebecca; Wong, KY; Chan, Kwok–Wah; Cheng, Ignatius K.P.

doi:10.1159/000188739

Cited by 75 publications

(79 citation statements)

References 15 publications

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“…All the patients recruited in this study were given low-dose continuous oral CYC treatment at a dose of 1-2 mg/day for 4-12 months for the treatment of severe organ manifestations of SLE. This was followed by a substitution to azathioprine (1-2 mg/kg/day) (22). Prednisone (1 mg/kg/day) was also started concomitantly and maintained for 8-10 weeks, after which it was gradually tapered down to a maintenance dose of around 7.5 mg/day.…”

Section: Methodsmentioning

confidence: 99%

Ovarian failure and flares of systemic lupus erythematosus

Mok

Wong

Lau

1999

Arthritis & Rheumatism

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Objective. To study the effects of ovarian failure on disease flares in systemic lupus erythematosus (SLE).Methods. Fifty-four female premenopausal SLE patients who were under the age of 45 years and treated with continuous oral cyclophosphamide (CYC) for no more than 12 months were studied. All patients had been followed up for >5 years following CYC treatment. Demographic characteristics, clinical and serologic profiles, and information concerning disease flares were recorded. Comparison of the number of severe and mild/moderate flares during the first 5 years after CYC treatment was made between patients who developed CYC-induced ovarian failure and those who did not.Results. Fourteen SLE patients had documented ovarian failure with hypoestrogenemia within 2 years after CYC treatment. Compared with the menstruating group of patients, those who developed ovarian failure were significantly older at the time of CYC therapy (mean 37.9 versus 25.5 years; P < 0.001), but otherwise no significant differences in organ manifestations and autoantibody profiles between the 2 groups were observed. Both the ovarian failure group and menstruating group of patients had similar SLE Disease Activity Index scores at the time of CYC treatment (mean 15.6 versus 17.7; P ‫؍‬ 0.16), and had comparable treatment durations (mean 8. Conclusion. This study provides an important clinical observation to support the notion that ovarian failure with hypoestrogenemia is protective against lupus flares and emphasizes the importance of estrogen status in the determination of disease activity in SLE.

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Section: Methodsmentioning

confidence: 99%

Ovarian failure and flares of systemic lupus erythematosus

Mok

Wong

Lau

1999

Arthritis & Rheumatism

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“…There is a considerable amount of data on the use of oral CYC, for defined durations up to 6 months, in Asian LN patients. Induction treatment with prednisolone and oral CYC could achieve complete or partial remission rates of 55-77% and 22-28%, respectively, within the first year, and a cumulative complete response rate of over 80% after 91.7 ± 36.7 months [19,34,35]. Although hemorrhagic cystitis can be prevented to a large extent by limiting the treatment duration and cumulative exposure to CYC, other adverse effects of CYC remain significant concerns, such as gonadal toxicity and late-onset neoplasms.…”

Section: Current Immunosuppressive Treatments For Ln: An Asian Perspementioning

confidence: 99%

Lupus Nephritis in Asia: Clinical Features and Management

Yap

Chan²

2015

Kidney Dis

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Background: Lupus nephritis (LN) is a common and severe organ involvement manifesting itself in systemic lupus erythematosus (SLE). There is a considerable difference in prevalence, severity, treatment response and outcomes between Asian LN patients and LN patients from other racial backgrounds. Summary: Asian SLE patients have a higher prevalence of LN than Caucasian SLE patients and often present with a more severe disease. Increasing data from genetic studies, accompanied by progress in high-throughput genotyping, have advanced our knowledge about genetic predispositions that might partly contribute to the clinical variations observed. Corticosteroids combined with either cyclophosphamide (CYC) or mycophenolic acid (MPA) is the current standard-of-care induction regimen for severe LN irrespective of race or ethnicity. However, the preference for MPA or CYC, and possibly the optimum dose for MPA, is influenced by the patient's origin. Also, there is an insufficient evidence base for reduced-dose intravenous CYC in Asian patients. Health economics and access to prompt diagnosis and treatment are still challenging issues in some Asian regions. The former represents a significant obstacle limiting the access of patients to MPA despite the proven efficacy of the drug as an induction agent and its superiority over azathioprine (AZA) in preventing disease flares when used for long-term maintenance immunosuppression. Calcineurin inhibitors such as tacrolimus deserve further investigation in view of their additional effect on podocytes by reducing proteinuria and the promising data from Asian patients. Despite considerable advances in the clinical management of LN over the past few decades with resultant improvements in patients' outcomes, there are still knowledge gaps and unmet clinical needs. Asia has made substantial contributions to the evidence base that guides clinical management and continues to offer invaluable opportunities for research pursuits. Key Messages: Treatment responses and clinical outcomes in Asian patients with LN compare favorably with patients from other parts of the world. The prevention and treatment of infective complications remain significant challenges in managing LN in Asia. Facts from East and West: (1) The prevalence of SLE is lower among Caucasians than other ethnicities. A higher prevalence is observed among Asians and African Americans, while the highest prevalence is found in Caribbean people. The prevalence of LN in Asian SLE patients is much higher than in Caucasians as well. However, the 10-year renal outcome and renal survival rate appear to be better in Asians. (2) Polymorphisms of genes involved in the immune response, such as Fcγ receptor, integrin alpha M, TNF superfamily 4, myotubularin-related protein 3 and many others, might be partly responsible for the differences in prevalence between the different ethnic groups. European ancestry was shown to be associated with a decrease in the risk of LN even after adjustment for genes most associated with renal disease. (3) Access...

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“…15,16 Reviewing studies on systemic lupus erythematosis and lupus nephritis, no cases of pancreatitis were documented in two studies. 17,18 Also, in a recent study with patients with vasculitis associated with antineutrophil cytoplasmic autoantibodies treated with azathioprine, pancreatitis is not mentioned as an adverse event. 19 In this study, we evaluated the occurrence of azathioprine-induced acute pancreatitis in patients with Crohn's disease and compared this with the incidence of acute pancreatitis in other diseases for which azathioprine is indicated.…”

Section: 12mentioning

confidence: 99%

Increased incidence of azathioprine‐induced pancreatitis in Crohn's disease compared with other diseases

Weersma¹,

Peters²,

Oostenbrug³

et al. 2004

Aliment Pharmacol Ther

107

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Summary Background : Azathioprine is widely used in Crohn's disease. A major drawback is the occurrence of side‐effects, especially acute pancreatitis. Acute pancreatitis is rarely seen when azathioprine is used for other diseases than Crohn's disease. Aim : To survey side‐effects of azathioprine after liver or renal transplantation, for systemic lupus erythematosis, Wegener's granulomatosis, autoimmune hepatitis, rheumatoid arthritis, ulcerative colitis or Crohn's disease. Methods : A computerized search using the term ‘azathioprine’ or ‘imuran’ was performed on the Hospital Information System of the university hospital Groningen, resulting in 1564 patients matching our criteria. Results : Eleven of 224 patients with Crohn's disease experienced acute pancreatitis (4.9%) compared with two of 129 (1.5%) with autoimmune hepatitis, two of 388 (0.5%) after renal transplantation, one of 254 (0.4%) after liver transplantation. Acute pancreatitis was more prevalent in Crohn's disease compared with any other disease. Azathioprine‐toxicity necessitating withdrawal occurred significantly (P < 0,05) more in rheumatoid arthritis(78 of 317), ulcerative colitis (20 of 94) and Crohn's disease (52 of 224) compared with systemic lupus erythematosis (five of 73), Wegener's granulomatosis (six of 85), autoimmune hepatitis (eight of 129), after liver transplantation (17 of 254) and after renal transplantation (22 of 388). Conclusions : Acute pancreatitis is strongly associated with Crohn's disease and rarely occurs with other underlying conditions. Overall azathioprine‐induced toxicity and the necessity of withdrawal is more common in inflammatory bowel disease and rheumatoid arthritis compared with other diseases.

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Sequential Therapy for Diffuse Proliferative and Membranous Lupus Nephritis: Cyclophosphamide and Prednisolone Followed by Azathioprine and Prednisolone

Cited by 75 publications

References 15 publications

Ovarian failure and flares of systemic lupus erythematosus

Ovarian failure and flares of systemic lupus erythematosus

Lupus Nephritis in Asia: Clinical Features and Management

Increased incidence of azathioprine‐induced pancreatitis in Crohn's disease compared with other diseases

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