Ovarian Function Preserved In Women With Severe Systemic Lupus Erythematosus When Treated With Cyclophosphamide And Mycophenolate Mofetil

Main Category: Lupus
Also Included In: Women's Health / Gynecology;  Fertility
Article Date: 13 Jun 2008 - 1:00 PDT

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Ovarian function can be preserved and disease activity controlled in women with severe systemic lupus erythematosus (SLE) when treated with a 6- month course of cyclophosphamide (CYC), a chemotherapy drug, followed by the immunosuppressant mycophenolate mofetil (MMF), according to a new study presented at EULAR 2008, the Annual Congress of the European League Against Rheumatism in Paris, France.

SLE, a complex and unpredictable autoimmune disease, is characterised by chronic inflammation and damage of body tissues, including the heart, lungs, kidneys, joints, and/or nervous system. It is most common in women and, although long-term survival has dramatically improved over time with better diagnosis and treatment options, one of the challenges in managing the disease is to minimise the side-effects of treatments such as the disruption of ovarian function and risks to fertility. Pulsed intravenous CYC, a chemotherapeutic agent, is a standard therapy for SLE but may also be associated with ovarian failure in addition to other adverse effects.

Dr Katerina Laskari, the presenting author of the study, led by Professor Athanasios G Tzioufas in the Department of Pathophysiology of the National and Kapodistrian University of Athens, said: "Although the prognosis for people with SLE has considerably improved over the years, a patient's quality of life can all too often be seriously impaired by the toxicity of many commonly- used treatments. Preserving ovarian function is a very important consideration in treating women with SLE of child-bearing age, who are already burdened by the difficult nature and impact of the disease itself."

In this retrospective evaluation of 61 postmenopausal women with SLE treated for lupus nephritis (n=58), autoimmune hemolytic anemia (n=1) and central nervous system involvement (n=2), 39 patients received prolonged treatment with 1g/m2 intravenous (IV) CYC pulses (group A) for a median time of 24 months and 22 patients received 5-7 monthly 1g/m2 IV CYC pulses, followed by 2g/day MMF for a median time of 32 months (group B).

Results showed that disease activity was equally controlled using either treatment regimen (p=0.76 and p=0.31 for disease remission and relapse respectively), although patients in group A had a 4-fold higher risk of developing amenorrhea (absence of menstruation) compared with those in group B (p=0.001). 56% (n=22) of women in group A and 14% (n=3) in group B developed amenorrhea, while sustained amenorrhea developed in 51% (n=20/39) of women in group A vs 4% (n=1) in group B. 14% (3/22) of women in group A and 67% (2/3) in group B resumed menstruation following cessation of therapy.

Age (p<0.001), cumulative CYC dose (p=0.001) and anti-Ro antibodies (p=0.002) were significant in terms of amenorrhea. Sustained amenorrhea was related to both the form of treatment (p=0.006) and the age of the patients (p=0.026). The median total CYC dose until amenorrhea was 11 gr (range 2-29.5) and 3.7 gr (range 2-6.75) in group A and B respectively (p=0.036).

The median age of women with amenorrhea was 36 years (range 19-46) in group A and 33 years (range 27-45) in group B (p=0.71). It is of note that all patients aged >31 years developed amenorrhea with the long course CYC treatment and 94% did not resume menses until the end of follow up, whereas only 1 patient aged 45 years developed permanent amenorrhea with the short course CYC treatment.

SLE disease duration and ECLAM (European Consensus Lupus Activity Measurement) score were not significantly different in terms of amenorrhea (p≥0.05).

About EULAR

The European League Against Rheumatism (EULAR) is the organisation which represents the patient, health professional and scientific societies of rheumatology of all the European nations.

The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.

Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 - 5 % of the adult population and are predicted to rise as people live longer.

As new treatments emerge and cellular mechanisms are discovered, EULAR 2008 brings together more than 12,000 experts - scientists, clinicians, healthcare workers, pharmaceutical companies and patients - to share their knowledge in a global endeavour to challenge the pain and disability caused by musculo-skeletal disorders.

Author:
Dr Katerina Laskari

To find out more information about the activities of EULAR, visit: http://www.eular.org