Many with lupus are at high risk of adverse drug reactions for pneumocystic pneumonia

New research shows that adults with systemic lupus erythematosus, who are receiving trimethoprim-sulfamethoxazole (TMP-SMX), a prophylactic therapy to help prevent pneumocystic pneumonia, are at high risk for adverse drug reactions, particularly if they are also positive for anti-Smith Antibodies (anti-Sm). The details of the study were presented at ACR Convergence, the annual meeting of the American College of Rheumatology (ABSTRACT # 1830).

Systemic lupus erythematosus, referred to as SLE or lupus, is a chronic (long-term) disease that causes systemic inflammation that affects multiple organs. In addition to affecting the skin and joints, it can affect other organs in the body such as the kidneys, the pleural tissue that lines the lungs or the heart and brain. Many lupus patients experience fatigue, weight loss, and fever.

Pneumocystis pneumonia, is an infection that can be life-threatening for people whose immune systems are suppressed by drugs for autoimmune diseases, including connective tissue diseases. These patients can be treated with drugs such as steroids or other immunosuppressants. One way to help prevent pneumocystis pneumonia infection is prophylactic treatment with the drug TMP-SMX, which is an antibiotic used to treat a variety of bacterial infections. It is effective but can cause adverse drug reactions in people with connective tissue diseases, and previous research shows that people with SLE are particularly at risk for these severe drug reactions.

“Patients with moderate to severe SLE usually require a high dose of corticosteroids and various types of immunosuppressants, creating a risk of developing pneumocystis pneumonia,” says study co-author Shinji Izuka, MD, a rheumatologist and researcher at the National Center for Health and Global Medicine in Tokyo. “Unlike HIV patients, who are also at high risk for pneumocystic pneumonia, patients with connective tissue diseases such as SLE are at risk of death when they develop this infection, so prophylaxis is important. Also, because of the disease. pandemic COVID-19, is important to prevent pneumocystis pneumonia for patients on immunosuppressants, because the symptoms and images are similar to COVID-19. Fortunately, TMP-SMX can effectively prevent pneumocystis pneumonia. “

Because previous studies suggested that lupus patients were at increased risk for adverse drug reactions, Dr Izuka’s team launched this study to confirm the risk and find out any specific risk factors. among people with SLE and other connective tissue diseases.

Researchers looked at their hospital’s inpatient database for records of patients with connective tissue disease who had been given TMP-SMX as a prophylactic agent against pneumocystis pneumonia between January 2009 and April 2020. The baseline data is were obtained at the time TMP-SMX was started. Patients with HIV and anyone who did not experience adverse drug reactions within one month were excluded. They compared the prevalence of adverse reactions between people with lupus and those with other connective tissue diseases and also analyzed data for any specific risk factors in lupus patients.

The 427 patients in the study included 164 with lupus, while the rest had another connective tissue disease, such as polymyositis or dermatomyositis, Sjögren’s syndrome, systemic sclerosis, mixed connective tissue disease, and several forms of vasculitis. Forty, or 9.4%, of patients developed an adverse drug reaction to TMP-SMX, including 10 with thrombocytopenia, nine with rash, seven with liver function test abnormalities, seven with fever, and 12 with other reactions.

People with lupus were more likely to have an adverse drug reaction: 13.4% compared to 6.9% in the control group patients. Their odds ratio of developing an adverse drug reaction was 2.12. When the researchers performed a univariate analysis to look for risk factors, they found that lupus patients with anti-Sm, anti-RNP, and anti-Ro / SS-A antibodies were significantly associated with a higher risk of an adverse drug reaction. Then, they performed a multivariate analysis and found that only anti-Sm antibodies were significantly associated with a higher risk in people with lupus.

Because of these increased risks, SLE patients receiving prophylactic TMP-SMX should be closely monitored for any adverse drug reactions, particularly those with anti-Sm antibodies, the researchers concluded.

“In these cases, it may be better to choose other options,” says Dr. Izuka. “The important thing is, however, that there were no patients in our study who developed serious conditions, such as Stevens-Johnson syndrome, due to adverse drug reactions to TMP-SMX. We shouldn’t hesitate to start TMP- SMX for those who The mechanisms of the association between adverse drug reactions and anti-Sm antibodies remain unclear. Further studies are needed to identify them and other undisclosed factors. In addition, we should clarify the best way to prevent pneumocystis pneumonia for patients. SLE patients with anti-sm antibody and other autoantibodies for safety and efficacy. ”