Taken together, two new prospective studies demonstrate that oral contraceptives (OCs) are safe in women with systemic lupus erythematosus (SLE) and may represent a paradigm shift in the thinking and clinical practice of rheumatologists who historically have been reluctant to prescribe OCs and other hormones for these patients. Both studies appear in the December 15, 2005, issue of the New England Journal of Medicine.^1,2

Reluctance to prescribe OCs and other hormones for women with lupus emerged in part from evidence that the disease is far more common in women and typically begins during childbearing years, when female hormone levels are at their peak. In murine models of lupus, the administration of estrogen was shown to exacerbate the condition and, depending on the genetic background of the patient, to influence the activity of B cells.

However, in the Oral Contraceptives–Safety of Estrogens in Lupus Erythematosus National Assessment (OC-SELENA) trial,¹ a 15-center study of 183 women with either inactive or stable lupus, funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), women taking OCs (triphasic 35 µg ethinyl estradiol/0.5–1 mg norethindrone for twelve 28-day cycles) showed no statistically significant difference in the occurrence of flares than those taking a placebo. Specifically, severe flares occurred in approximately 8% of the women, regardless of whether they had received OCs or placebo.

A second single-blind study² found that the incidence of adverse events (including global disease activity, maximum Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] score, incidence of flares, and time-to-first flare) was similar in women with SLE, irrespective of the form of contraception they had been using (combined OCs, progestin-only pills, or intrauterine device [IUD]).

Studies support use of OCs in SLE patients without clotting risks

OC-SELENA co-primary authors Jill Buyon, MD, a rheumatologist at the New York Hospital for Joint Diseases in New York City, and Michelle Petri, MD, MPH, a rheumatologist at Johns Hopkins University School of Medicine in Baltimore, Maryland, tell CIAOMed that these new data may change clinical practice. "Most clinicians have been concerned about using oral contraceptive pills (OCPs) to the point of not [prescribing them]," they say. "These studies support the use of OCP in women who do not have any additional clotting risks and whose disease is currently stable. However, it should be added that [even] for women with SLE who are in a severe flare, OCP might still be considered when their disease is under better control."

Oral contraceptives are not indicated in "women who have antiphospholipid antibodies or [who are] at high risk of having a blood clot," Drs. Buyon and Petri tell CIAOMed. "Clearly, smoking is not a good combination with OCP, and is really contraindicated if over age 35."

In OC-SELENA, the rates of mild-to-moderate flares and disease complications were also similar between the OC and placebo groups over the 12-month follow-up. "Estrogen, as used in this study, appears to be safe in the majority of women with stable disease," NIAMS Director Stephen I. Katz, MD, PhD, noted in a written statement. "This research brings us another step forward in improving quality of life for people with rheumatic disease."

In the single-blind clinical trial of 162 women with SLE who were randomly assigned to a combined OC, progestin-only pill, or a copper IUD, Sánchez-Guerrero et al found no significant differences among the groups during the trial in rates of global or maximum disease activity, incidence or probability of flares, or medication use. The median time to first flare was 3 months in all groups. Thromboses occurred in four patients (two in each of the two groups receiving hormones), and severe infections were more frequent in the IUD group. One patient receiving combined OCs died from amoxicillin-related severe neutropenia.

Reasons for OC use in SLE are numerous

In an accompanying editorial,³ Bonnie L. Bermas, MD, a rheumatologist at Brigham and Women's Hospital in Boston, Massachusetts, writes that there are several sound reasons for prescribing OCs in women with SLE—notably that planned pregnancies and conception during remission have better outcomes. Also, Dr. Bermas writes, "patients with very active disease or those receiving potentially teratogenic medications should use an extremely reliable form of birth control." In addition to preserving ovarian function and mitigating the infertility that can result from cyclophosphamide therapy in SLE, oral contraceptives "may reduce bone loss and [the] attendant osteoporosis that can be seen in patients treated with glucocorticoids," she writes.

Findings may change clinical practice

John Klippel, MD, CEO of the Arthritis Foundation in Atlanta, Georgia, tells CIAOMed that he hopes the new findings change clinical practice. "These studies provide supportive data to assure people that birth control, including use of estrogens in lupus, is actually safe," Dr. Klippel says. "The majority of patients are not cared for in academic centers, so having this data is very important."

Thirty years ago, lupus patients were told that they should never become pregnant and that they could not use birth control, Dr. Klippel points out. Yet there has been a significant decrease in pregnancy loss among women with SLE over the past 40 years, largely due to improvements in perinatal monitoring and disease management, according to a study⁴ recently reported by CIAOMed. The study also showed a trend toward decreased preterm deliveries over the last 20 years in comparison to the general population.

Ob/gyn community welcomes new data

"I have used birth control in lupus for years in consultation with rheumatologists and nephrologists, unless the patients have clotting issues," says Mary Jane Minkin, MD, clinical professor of obstetrics and gynecology at Yale University School of Medicine in New Haven, Connecticut.

"The other patients I would be concerned with are those with serious kidney involvement, but we don't want these patients to get pregnant either," Dr. Minkin tells CIAOMed. "If oral contraceptives are the only contraception they will use, then I will use it with trepidation in conjunction with a rheumatologist and nephrologist," she says. "It is nice that we have large-scale studies to verify that the use of contraceptives in SLE is a good thing, and safe."

References

1. Petri M, Kim MY, Kalunian KC, et al. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med. 2005;353:2550-2558.
2. Sánchez-Guerrero J, Uribe AG, Jiménez-Santana L, et al. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med. 2005;353:2539-2549.
3. Bermas BL. Oral contraceptives in systemic lupus erythematosus—a tough pill to swallow? N Engl J Med. 2005;353:2602-2604.
4. Clark CA, Spitzer KA, Laskin CA. Decrease in pregnancy loss rates in patients with systemic lupus erythematosus over a 40-year period. J Rheumatol. 2005;32:1709-1712.