For patients who have a good response, the goal is to taper to 10 mg daily or less, a practice endorsed by a Delphi consensus study of sarcoidosis management (Respir. Med. 2010; 104:717-23).
“That's evolving as an important target for long-term management of sarcoidosis patients,” he noted, and it also helps minimize steroid adverse effects.
When patients have an inadequate response to prednisone or are unable to reduce the dosage to 10 mg daily, the algorithm suggests adding an immune modulator (methotrexate, azathioprine, leflunomide, or mycophenolate) to therapy.
“The choice of immune modulators … is really dealer's choice,” Dr. Culver commented. “Suffice it to say that it's most important that you become comfortable with something and you are used to how to use it, more so than necessarily exactly which one to use.”
There have been few head-to-head comparisons of these agents, although methotrexate is by far the agent preferred by U.S. physicians treating sarcoidosis, partly because it has been the best studied.
“That's the drug that we use as our second-line agent,” Dr. Culver noted. “The reason that we like methotrexate is it seems to work pretty well, it's pretty inexpensive and pretty reliable, and it's not hard to get through the insurance company.”
Data from his institution show that leflunomide also works well. A review of 40 patients with pulmonary sarcoidosis found they had an improvement in FVC within 6 months of starting this drug (P = .01), as well as a reduction in the average prednisone dose to 5 mg daily.
“So we have really moved leflunomide to the next agent in our algorithm after methotrexate,” he said.
Infliximab is the only agent that has been shown to be efficacious in a double-blind, randomized controlled trial of patients with sarcoidosis, according to Dr. Culver.
In unselected patients, infliximab is associated with just a 2.5% improvement in percent predicted FVC (Clin. Chest Med. 2008;29:533-48, ix-x) – or about that seen with steroids. But among the subset having more severe lung disease, with an FVC of less than 69%, there is a roughly 3.25% improvement. The improvement was 6% in the randomized trial (Sarcoidosis Vasc. Diffuse Lung Dis. 2006;23:201-8).
“So, in fact, we think for patients failing cytotoxic agents that infliximab is a nice option,” Dr. Culver commented.
And studies are helping to identify which patients are most likely to benefit from infliximab: those who have had disease for more than 2 years, have worse dyspnea (a Medical Research Council dyspnea score of at least 2), lower FVC, poorer quality of life (assessed with the St. George's Respiratory Questionnaire), reticulonodular changes on their chest x-ray, or an elevated C-reactive protein level.
“In fact, these are some of the same entry criteria that are being used for the current trial of biologics in sarcoidosis, trying to target that more severe patient population,” he noted.
In concluding, Dr. Culver advised physicians to establish and keep in mind the goals of treatment, and to remember the chronic nature of sarcoidosis.
“If I can leave you with one thing, the message is … you have to sit and talk to your patient and find out what's important to them, what do they want to accomplish,” he said.
“That's the best thing that you can do as you think about treating your patient longitudinally, because remember, you are not treating this as if it's an infection, you are treating this as if it's hypertension that needs to be controlled in the long term.”
Dr. Culver reported having affiliations with the biotechnology and pharmaceutical companies Centocor (manufacturer of infliximab), Takeda, and Actelion.
'If the symptoms are relatively mild or modest … then I think observation is completely reasonable.'
Source DR. CULVER