Should Antimalarial Drugs Such as Hydroxychloroquine Be Used in People with Systemic Lupus Erythematosus
Introduction:
Antimalarial drugs are used to treat malaria. But, in the second World War there was a report suggesting that they also improved arthritis. Subsequent studies confirmed their value in both rheumatoid arthritis and SLE. It was learned that when hydroxychloroquine (Plaquenil) is stopped in people with SLE, they are more likely to have a flare-up in their lupus. Occasionally, these flare-ups can be severe.
It is never possible to be 100% certain that any drug is safe during pregnancy. This study was done to get the opinion of real lupus experts from around the world on how safe they thought hydroxychloroquine was in pregnancy, whether they used it in people with lupus who were pregnant, and whether they had ever seen a side effect in the baby such as a birth defect.
Project Methodology:
We searched all of the English language medical journals for individuals who had published on hydroxychloroquine, SLE, and pregnancy for 1966-1999 as well as going through textbooks on arthritis to find who had written chapters on lupus. The experts were mailed a 19-question survey asking them about themselves and their practice and how they managed individuals with SLE during pregnancy and breast feeding.
Relevance For People With Arthritis:
The results reported are consistent with studies following women with lupus who have become pregnant taking antimalarials such as hydroxychloroquine. Thus, the fact that a number of studies that have followed these women have not found any toxicity is reassuring. However, one would need a much larger number of cases to feel even reasonably certain that the benefits of hydroxychloroquine in preventing flare-ups outweighed the unknown risks. The fact that the majority of lupus experts feel the drug is safe and that they have not seen any toxicity is good news. Every year, these experts see about 200 women with lupus who are pregnant.
Results:
78 experts were identified. There were 24 from Canada, 31 from the United States, 5 from Mexico and 18 from the United Kingdom. Out of 78, 74% relied to the questionnaire. Three-quarters of those who replied were male physicians and their average age was 51 years old. The typical doctor who replied followed at least 75 people with SLE each and had four or five of their patients become pregnant every year.
Survey results found:
- 42% said they often or always continued antimalarials drugs during pregnancy,
- 27% said sometimes,
- and 32% said never or rarely.
The more pregnant persons with SLE that the individual physician cared for, the more likely they were to continue hydroxychloroquine in pregnancy. Also, the more recently the individual had graduated from medical school, the more likely they were to continue the hydroxychloroquine. Those physicians who tended to continue hydroxychloroquine during pregnancy were also significantly more likely to start hydroxychloroquine during pregnancy for a flare-up in women who were not taking it.
None of the physicians reported having ever seen any problems to a baby with antimalarial use.
When the issue of breast feeding was raised, two-thirds of the physicians advised the patient to continue antimalarials throughout breast feeding and about a quarter suggested continuing antimalarials, but bottle feeding the baby. Only 13% stopped antimalarials. It is known that very little hydroxychloroquine gets into breast milk.
Time Frame:
This study took about one year to get Ethics approval and to complete the data collection and analysis. It then took about 4 months to write up and 8 months to get published in a major scientific journal.
Funding Agency:
Division of Rheumatology, University of British Columbia.
Related Studies:
John Esdaile had previously led several other several studies that demonstrated that hydroxychloroquine (Plaquenil) was of benefit in both rheumatoid arthritis and SLE and that its use prevented flare-ups and delayed the progress of disease. The relevant publications are:
- Canadian Hydroxychloroquine Study Group. A randomized withdrawal trial of hydroxychloroquine sulfate in systemic lupus erythematosus. New Engl J Med 1991;324:150-154.
- The HERA Study Group. A randomized trial of hydroxychloroquine in early rheumatoid arthritis: The HERA study. Am J Med 1995;98:156-168.
- The Canadian Hydroxychloroquine Study Group. A long-term study of hydroxychloroquine withdrawal on exacerbations in systemic lupus erythematosus. Lupus 1998;7:80-85.
- Tsakonas E, Fitzgerald AA, Fitzcharles M-A, Cividino A, Thorne JC, M’Seffar A, Joseph L, Bombardier C, Esdaile, JM. Consequences of delayed therapy with second-line agents in rheumatoid arthritis (HERA) study. J Rheumatol 2000;27:623-9.
Publications
- Al-Herz A, Schulzer M, Esdaile, JE. Survey of antimalarials in lupus pregnancy and lactation. J Rheumatol 2002;29:700-706.
Project Team Members
Principal Investigator
Adeeba Al Herz MBBS, FRCPC, ABIM Rheumatology Fellow,
Division of Rheumatology
University of British Columbia
Arthritis Research Centre of Canada
Co-Investigators
Michael Schulzer MD, PhD
Professor, Departments of Medicine and Statistics,
University of British Columbia
John M. Esdaile MD MPH, FRCPC
Scientific Director, ARC
Professor and Head, Division of Rheumatology
University of British Columbia