Reviewing ERS Treatment Guidelines in Sarcoidosis

As interest grows in addressing health care disparities, a rare condition known to affect populations unevenly is sarcoidosis, a rare condition that causes tiny inflammatory cells called granulomas to appear in the body, especially in the lungs and lymph nodes.

According to the Mayo Clinic, researchers are not entirely sure what causes sarcoidosis, but it is believed to be a triggered by the body’s immune response to an unknown substance. Possible culprits are infectious agents, chemicals, or allergens; for some, a genetic predisposition may be causing the body to react against its own proteins.

What is known is that sarcoidosis affects some populations more than others. According to the American Lung Association, in the United States, Black individuals are 3 times more likely to develop the disease than White individuals, and women are more likely to develop it than men. Besides the lungs and lymph nodes, the disease can also affect the eyes, skin, heart, and other organs; morbidity can be significant, and the disease can be fatal.

Initial treatment for sarcoidosis typically involves glucocorticoids (GCs), but prolonged use can cause other issues due to toxicity. Thus, in 2021 a task force of the European Respiratory Society developed and released treatment recommendations based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology to guide decision making.¹

Task force members developed 8 prompts used to direct evidence-based recommendations, which they called PICO (Patients, Intervention, Comparison, Outcomes) questions. Members were asked to declare conflicts and not take part in discussions that might present a conflict.

The process resulted in 12 recommendations for 7 of the PICO questions. The task force then presented algorithms for the various scenarios outlined in the questions, covering therapy (or device) options in pulmonary, skin, and cardiac sarcoidosis, symptomatic neurosarcoidosis, and sarcoidosis-associated fatigue.

An algorithm was presented for small-fiber neuropathy–related symptoms based on current practice; however, in response to the PICO question, the committee said current evidence is insufficient to make formal recommendations.

The committee noted that treatment of patients with sarcoidosis is very challenging. “The clinician must remember not to focus on a single manifestation, but to look at the various manifestations both initially and over time,” the committee wrote.

Outcomes are highly variable; although the mortality rate is less than 10%, at least 25% require treatment for more than 2 years. The disease can recur if treatment is withdrawn too early, the task force noted, and these decisions are very difficult.

Task force members also developed a table with various treatment choices that described toxicity and risk of comorbidities.

Pulmonary Sarcoidosis

This algorithm was derived from a systematic review of 1747 potentially relevant articles, of which 36 were reviewed and 19 selected for inclusion. A total of 134 patients were covered by the studies. Of all the algorithms presented, this offered the highest number of options.

The provider is first asked to determine if a patient is low risk, intermediate risk, or high risk. Considerations are minimizing the risk of disability, lost of life due to pulmonary involvement or loss of quality of life, or risk of comorbidities due to GCs or other therapies. In the case of pulmonary sarcoidosis, interstitial lung disease or pulmonary hypertension are major risks and the chief causes of disease-related mortality. Scenarios flow as follows:

Low risk. Patients should be placed under observation. If treatment is needed, prescribe GCs; this is a strong recommendation.

Intermediate risk, but impaired quality of life. Most of the algorithm is based on current practice; tapering off therapies with GCs is recommended after good clinical responses.

• Start with GCs, if there is a good clinical response, eventually taper off GCs. If there are GC side effects, continued disease, or relapse, then choices are methotrexate, azathioprine, leflunomide, mycophenolate mofetil, or hydroxychloroquine.
• If there is a good clinical response, eventually taper with GCs. If there is continued disease or relapse, options are infliximab or adalimumab. If there is a good clinical response, eventually taper with GCs.
• If there is continued disease or relapse, options are rituximab, JAK inhibitor, or repository corticotropin injection (RCI) on a case-by-case basis. If there is a good response, eventually taper with GCs.

High risk. Follows similar algorithm as intermediate risk, except that methotrexate in second-line treatment has a conditional recommendation (based on a very low quality of evidence); infliximab in third-line treatment has conditional recommendation (based on a low quality of evidence).

Task force members called for more research to “evaluate the efficacy, safety, and cost efficiency” of rituximab, RCI, anti–tumor necrosis factor biosimilars, other immunosuppressive agents, and antifibrotic agents such as nintedanib and pirfenidone. The members write that newer end points, including change in quality of life, must be validated.

“We do not feel these guidelines are the final word on the management of sarcoidosis,” the authors wrote, noting the task force made “informed recommendations” based on current evidence and clinical experience. Task force members were candid where evidence is lacking, however.

“We anticipate that an update of this guideline will be needed within the next 5 years as more information becomes available,” they wrote.

Reference

1. Baughman RP, Valeyre D, Korsten P, et al. ERS clinical practice guidelines on treatment of sarcoidosis. Eur Respir J. 2021;58:2004079. doi:10.1183/13993003.04079-2020