Infliximab for Rheumatoid Arthritis in a Patient with Tuberculosis
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《新英格兰医药杂志》
To the Editor: Tumor necrosis factor antagonists have been shown to be effective agents in the treatment of rheumatoid arthritis; however, they have also been shown to increase the risk of the reactivation of tuberculosis in patients with latent infection1,2 and may render the tuberculosis refractory to drug therapy.3,4 Decisions regarding the treatment of patients with refractory rheumatoid arthritis in the setting of active tuberculosis remain difficult.
A 64-year-old woman with a 10-year history of rheumatoid arthritis (functional class III and radiologic stage 3, according to Steinbrocker's criteria) had begun treatment with infliximab at a dose of 3 mg per kilogram of body weight combined with prednisolone (10 mg per day), sulfasalazine (1000 mg per day), and methotrexate (8 mg per week) because of worsening joint symptoms (Figure 1). At baseline, she had a nonreactive tuberculin skin test with purified protein derivative, and the results of computed tomography of the chest were normal. After the third administration of infliximab, high fever and abdominal distention developed.
Figure 1. Clinical Course of a Woman with Rheumatoid Arthritis and Active Peritoneal Tuberculosis.
PPD denotes purified protein derivative.
The patient was referred to our hospital, and a diagnosis of peritoneal tuberculosis was established. A standard antituberculosis regimen was initiated (isoniazid, rifampin, pyrazinamide, and ethambutol), and prednisolone and methotrexate were continued without infliximab. Drug testing showed that the Mycobacterium tuberculosis collected from a specimen of abdominal fluid was susceptible to all the medications tested. Intensive antituberculosis therapy resulted in the resolution of the clinical signs and symptoms of peritoneal tuberculosis, but the cessation of infliximab was associated with a recrudescence of highly symptomatic rheumatoid arthritis four months later. Given the excellent clinical response of the tuberculosis to therapy and the limited therapeutic options for the treatment of the patient's severely symptomatic rheumatoid arthritis, infliximab therapy was resumed in conjunction with continuing antituberculosis medication.
The readministration of infliximab resulted in prompt improvement in the disease activity of the rheumatoid arthritis (Figure 1), meeting the criteria of the American College of Rheumatology for remission. No signs of a recurrence of the tuberculosis have been detected after more than one year of follow-up. This case report demonstrates that infliximab therapy can be considered for patients with refractory rheumatoid arthritis who have recovered from active tuberculosis and in whom antituberculosis therapy can be maintained.
Tomoshige Matsumoto, M.D.
Osaka Prefectural Medical Center for Respiratory and Allergic Diseases
Osaka 583-8588, Japan
tom_matsumoto@sutv.zaq.ne.jp
Toshio Tanaka, M.D.
Ichiro Kawase, M.D.
Osaka University Medical School
Osaka 565-0871, Japan
References
Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor-alpha neutralizing agent. N Engl J Med 2001;345:1098-1104.
Arthritis Advisory Committee. Update on the TNF- blocking agents. Rockville, Md.: Food and Drug Administration, 2003. (Accessed July 27, 2006, at http://www.fda.gov/ohrms/dockets/ac/03/briefing/3930B1_01_B-TNF.Briefing.doc.)
Taylor JC, Orkin R, Lanham J. Tuberculosis following therapy with infliximab may be refractory to antibiotic therapy. Rheumatology (Oxford) 2003;42:901-902.
Garcia Vidal C, Rodriguez Fernandez S, Martinez Lacasa J, et al. Paradoxical response to antituberculous therapy in infliximab-treated patients with disseminated tuberculosis. Clin Infect Dis 2005;40:756-759.
A 64-year-old woman with a 10-year history of rheumatoid arthritis (functional class III and radiologic stage 3, according to Steinbrocker's criteria) had begun treatment with infliximab at a dose of 3 mg per kilogram of body weight combined with prednisolone (10 mg per day), sulfasalazine (1000 mg per day), and methotrexate (8 mg per week) because of worsening joint symptoms (Figure 1). At baseline, she had a nonreactive tuberculin skin test with purified protein derivative, and the results of computed tomography of the chest were normal. After the third administration of infliximab, high fever and abdominal distention developed.
Figure 1. Clinical Course of a Woman with Rheumatoid Arthritis and Active Peritoneal Tuberculosis.
PPD denotes purified protein derivative.
The patient was referred to our hospital, and a diagnosis of peritoneal tuberculosis was established. A standard antituberculosis regimen was initiated (isoniazid, rifampin, pyrazinamide, and ethambutol), and prednisolone and methotrexate were continued without infliximab. Drug testing showed that the Mycobacterium tuberculosis collected from a specimen of abdominal fluid was susceptible to all the medications tested. Intensive antituberculosis therapy resulted in the resolution of the clinical signs and symptoms of peritoneal tuberculosis, but the cessation of infliximab was associated with a recrudescence of highly symptomatic rheumatoid arthritis four months later. Given the excellent clinical response of the tuberculosis to therapy and the limited therapeutic options for the treatment of the patient's severely symptomatic rheumatoid arthritis, infliximab therapy was resumed in conjunction with continuing antituberculosis medication.
The readministration of infliximab resulted in prompt improvement in the disease activity of the rheumatoid arthritis (Figure 1), meeting the criteria of the American College of Rheumatology for remission. No signs of a recurrence of the tuberculosis have been detected after more than one year of follow-up. This case report demonstrates that infliximab therapy can be considered for patients with refractory rheumatoid arthritis who have recovered from active tuberculosis and in whom antituberculosis therapy can be maintained.
Tomoshige Matsumoto, M.D.
Osaka Prefectural Medical Center for Respiratory and Allergic Diseases
Osaka 583-8588, Japan
tom_matsumoto@sutv.zaq.ne.jp
Toshio Tanaka, M.D.
Ichiro Kawase, M.D.
Osaka University Medical School
Osaka 565-0871, Japan
References
Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor-alpha neutralizing agent. N Engl J Med 2001;345:1098-1104.
Arthritis Advisory Committee. Update on the TNF- blocking agents. Rockville, Md.: Food and Drug Administration, 2003. (Accessed July 27, 2006, at http://www.fda.gov/ohrms/dockets/ac/03/briefing/3930B1_01_B-TNF.Briefing.doc.)
Taylor JC, Orkin R, Lanham J. Tuberculosis following therapy with infliximab may be refractory to antibiotic therapy. Rheumatology (Oxford) 2003;42:901-902.
Garcia Vidal C, Rodriguez Fernandez S, Martinez Lacasa J, et al. Paradoxical response to antituberculous therapy in infliximab-treated patients with disseminated tuberculosis. Clin Infect Dis 2005;40:756-759.