Current Medical Therapy for Sarcoidosis

Dominique Valeyre, MD; Florence Jeny, MD; Hilario Nunes, MD, PhD

Disclosures

Semin Respir Crit Care Med. 2017;38(4):523-531. 

In This Article

Abstract and Introduction

Abstract

Most cases of sarcoidosis are mild and self-limited, with a spontaneous cure. However, in some patients, this disease may also be life-threatening, particularly when severe manifestations induce vital organ dysfunction. Sarcoidosis may also severely impair the quality of life through diverse, persistent disabling symptoms. To date, there is no curative treatment for sarcoidosis, but only anti-inflammatory drugs limiting the pathologic impact of sarcoidosis in reducing enhanced immunity reactions, granulomatous formation, and their consequences. Current anti-inflammatory treatments for sarcoidosis include corticosteroids as the first-line treatment; disease-modifying antisarcoid drugs, mainly immunosuppressive and immunomodulatory drugs, as second-line treatment; and finally tumor necrosis factor (TNF) inhibitors, as third-line treatment. Corticosteroids are most effective; they give rapid results, sometimes with serious, incremental adverse effects. A second-line treatment, mainly low-dose methotrexate and azathioprine, is indicated in case of corticosteroid resistance, intolerance, or contraindication or more often as a corticosteroid-sparing agent when a prolonged treatment of more than 10 mg/d equivalent prednisone is expected. TNF inhibitors are considered in severe refractory sarcoidosis. Infliximab has been proven effective. Usually, treatment for sarcoidosis lasts up to 1 year or longer. The usual drug regimen is made of an induction and then a maintenance protocol before a step-by-step decrease and eventual withdrawal. Contraindications may exist. Each therapeutic decision must follow a rigorous diagnostic evaluation to determine the disease impact, its outcome (progression or not), and its response to treatment in the long run. Pharmacogenetics is still in its infancy, but could help develop a more personalized therapy. Non anti-inflammatory treatments, such as implantable cardiac devices, are also useful, particularly for some organs. In the end, persistent disabling symptoms are very frequent and call for an accurate diagnosis, which may be difficult to treat.

Introduction

Sarcoidosis is a systemic disease of unknown cause characterized by the formation of granulomatous lesions in involved organs, usually with lung and lymphatic involvement. To date, there is still no treatment leading to a cure despite the knowledge that some causes are suspected to be at the origin of sarcoidosis.[1] Management is still based on either therapeutic abstention (when the disease is self-limited) or anti-inflammatory drugs that are able to slow down the enhanced immunity reaction responsible for granulomatous process but with only a suppressive effect. Three lines of drugs are available—schematically corticosteroids as the first line; disease-modifying antisarcoid drugs (DMASDs)—immunosuppressive agents and immunomodulators—as the second line; and tumor necrosis factor (TNF) inhibitors as the third line with the opportunity of combining drugs in some circumstances. The risks for sarcoidosis treatment vary from patient to patient. They include life-threatening risk of severe dysfunction; irreversible major organ damage; occurrence of incapacitating and constitutional symptoms; potential adverse effect; and susceptibility and the patient's preference, including desire of child-bearing, which call for clear and honest information. Evidence-based data are scarce since few randomized controlled trials have been conducted. Moreover, endpoints remain insufficiently validated, particularly for extrapulmonary manifestations.[2,3] No randomized controlled trial on anti-inflammatory drug has shown any survival benefits and few trials have been directed on quality of life or respective persistent disabling symptoms, although very frequent and often at the forefront, such as fatigue. Eventually, most trials were based on short-term endpoints, while the clinician would need information concerning responses and tolerance in the long term especially since many sarcoidosis patients are young.

Corticosteroids remain the cornerstone for the treatment of sarcoidosis particularly at induction with a rapid response in most patients and the potential occurrence of adverse events. These may be severe and increase with treatment duration mainly if high doses are necessary to control the disease. Immunosuppressive drugs, mainly low-dose methotrexate or azathioprine, are prescribed when corticosteroids are ineffective or poorly tolerated. A current trend is to propose more often and sooner immunosuppressive drugs as corticosteroid-sparing agents before the occurrence of corticosteroid adverse effects, particularly when the threshold dose for maintaining a response is over 10 mg/d of prednisone. TNF inhibitors are very powerful agents to consider when corticosteroids and DMASDs have failed.

Several excellent recent reviews have been devoted to sarcoidosis treatment.[4,5,6,7,8] Here, we chose to underscore practical aspects, particularly when safety is concerned.

This article includes three main parts: the first one on stakes to cope with when dealing with therapeutic options in sarcoidosis, the second one on the efficacy and safety of current anti-inflammatory drugs (Table 1), and the third one on the indications according to clinical situations.

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