SALT LAKE CITY — Infliximab is a highly effective and safe therapy for patients with multisystem sarcoidosis refractory to conventional immunomodulatory agents, Dr. Ghulam Khaleeq said at the annual meeting of the American College of Chest Physicians.
The tumor necrosis factor-α inhibitor is generally well tolerated in this setting, with minimal side effects, added Dr. Khaleeq of Drexel University, Philadelphia.
He presented a retrospective observational study involving 20 patients with refractory multisystem sarcoidosis in an outpatient pulmonary medicine practice who were placed on infliximab (Remicade) because of persistent symptoms or side effects on prednisone, methotrexate, and/or hydroxychloroquine.
The patients' mean age at the start of infliximab was 45 years, with a prior 11-year history of sarcoidosis since diagnosis. Seventeen of the 20 patients were women; 16 patients were African American. Seventeen had lung involvement, and 8 had CNS disease. Skin, joint, or lung manifestations were seen in 13, 11, and 9 patients, respectively. In addition, 7 patients had ocular disease, 5 hepatic, 4 bone, 3 sinus, and 2 renal.
The pulmonary disease was generally well controlled with conventional therapy. The chief reason patients went on infliximab was refractory bone or brain disease.
Sarcoidosis is an off-label use for infliximab. Dr. Khaleeq and his colleagues dosed the intravenous chimeric IgG monoclonal antibody using the standard protocol for Crohn's disease: 5 mg/kg at weeks 0, 2, and 6, then every 6 weeks thereafter.
All patients had marked and rapid improvement in symptoms. The gains have been maintained during an average of just less than 2 years of therapy. Nearly all patients were on at least 10 mg/day of prednisone at the outset, but by 6 months four patients had discontinued steroids and the rest had reduced their dosage.
Of two patients on 60 mg/day of prednisone at baseline, one was on 20 mg at 6 months and the other was off the steroid entirely. In addition, six patients were off methotrexate and three patients were off hydroxychloroquine.
Four patients developed mild side effects on infliximab: One had frequent upper respiratory tract infections, one developed leg pain, another experienced fatigue and night sweats, and one patient developed hemiplegia, which resolved with stress-dose steroids. No one has had to discontinue infliximab.
Audience members with expertise in using infliximab for refractory sarcoidosis confirmed Dr. Khaleeq's impression that when patients are refractory to conventional therapies, they are generally refractory at sites other than the lung.
The discussion period featured a lively debate about the value of prescribing methotrexate with infliximab to prevent formation of antibodies to the chimeric monoclonal antibody and subsequent anaphylaxis. One camp asserted that this common practice is based on unconvincing data and really isn't necessary. Dr. Robert P. Baughman took a somewhat different view.
“I think you can reasonably make an argument for stopping an immunomodulator if the patient is doing well on infliximab,” according to Dr. Baughman, professor of internal medicine at the University of Cincinnati. “Our bias is that methotrexate is not a very toxic drug if given in appropriate doses, so we tend to keep people on it. But certainly you have to ask if it's doing anything, especially after you get past that first 6 to 12 months. After that, the risk of anaphylaxis is going to be pretty low. Most cases occur by the fourth or fifth dose.”
Dr. Baughman was the principal investigator in a recent positive phase II randomized, double-blind, placebo-controlled trial of infliximab in 138 patients with chronic pulmonary sarcoidosis (Am. J. Respir. Crit. Care Med. 2006;174:795–802).
Infliximab is generally well tolerated in refractory sarcoidosis patients. DR. KHALEEQ