Off-label TNF-alpha Inhibitors May Ease Hard-to-treat Sarcoidosis
Treatment may prevent extrapulmonary sarcoidosis from worsening
Off-label use of TNF-alpha inhibitors may help some people with hard-to-treat sarcoidosis ease their symptoms or prevent them from getting worse, according to a meta-analysis study.
Data also showed that these inhibitors, particularly Remicade (infliximab), may work slightly better for patients who have symptoms of sarcoidosis also outside the lungs (extrapulmonary sarcoidosis) than for those who have only lung involvement (pulmonary sarcoidosis).
The study, “Role of anti-tumor necrosis factor-alpha agents in treatment of sarcoidosis: A meta-analysis,” was published in the European Journal of Internal Medicine.
TNF-alpha inhibitors used off-label by about 1 in 10 sarcoidosis patients in U.S.
Sarcoidosis occurs when white blood cells aggregate into small clumps, called granulomas, and cause inflammation (swelling) of body tissues. Most people with sarcoidosis experience problems in the lungs, often manifesting as shortness of breath and persistent dry cough.
Many do not need treatment, but if pharmacological treatment is recommended, it usually includes corticosteroids to help reduce inflammation. If corticosteroids are not enough or there are worries about side effects, other immunosuppressive treatments may sometimes be used.
While they are not approved for sarcoidosis, TNF-alpha inhibitors are used off-label by about one in 10 sarcoidosis patients in the U.S. who do not respond well to other medications.
TNF-alpha inhibitors work by blocking the activity of TNF-alpha, a molecule present in high amounts in inflamed tissues, where it helps prolong inflammation. By suppressing TNF-alpha, these treatments are expected to reduce inflammation. Efficacy data of anti-TNF-alpha treatments in hard-to-treat (refractory) sarcoidosis are “mixed and inconclusive,” the researchers wrote.
Although [TNF-alpha inhibitors] are the last option in treatment for some patients, they appear to be a practical and advantageous treatment option
Meta-analysis included a total of 398 sarcoidosis patients
To know more, a team of researchers in Iran and the U.S. performed a meta-analysis, a type of analysis that combines data from a number of different studies from the literature. They performed a systematic review of published studies up to April 10, 2022, that reported the efficacy of TNF-alpha inhibitors in people with pulmonary and extrapulmonary sarcoidosis in clinical trials.
Of the 22 studies assessed for eligibility, eight — involving a total of 398 sarcoidosis patients — were included in the meta-analysis. Most of these clinical trials were conducted in the U.S. Four tested Remicade, two used etanercept (sold as Enbrel, among others), one evaluated adalimumab (sold as Humira, with biosimilars also available), and one tested Simponi (golimumab) in combination with Stelara (ustekinumab).
Patients’ mean age was 48.5 years, and their treatment period ranged from 14 weeks (3.5 months) to 45 weeks (about 10 months). All medications were given as an under-the-skin injection, with the exception of Remicade, which was administered directly into the bloodstream.
Treatment success, defined as symptom reduction or no disease progression, was observed in 69.9% of people with pulmonary sarcoidosis. In those with extrapulmonary sarcoidosis, the rate was slightly better (74.5%).
When looking at treatment success rates across various organ involvements, Remicade appeared to work best, both for pulmonary sarcoidosis (80%–100% success rate) and extrapulmonary sarcoidosis (93%–100% success rate).
Etanercept was associated with a treatment success rate of 31% among pulmonary sarcoidosis patients and 66% for those with eye manifestations. In sarcoidosis-related skin lesions, adalimumab treatment reduced or stabilized symptoms in 60% of patients, while the Simponi-Stelara combo was associated with a success rate of 32%.
While the meta-analysis was limited to only a few clinical trials, “treatment of refractory sarcoidosis with [anti-TNF-alpha] agents was effective in both pulmonary and extrapulmonary sarcoidosis, with a slightly higher efficacy seen in extrapulmonary sarcoidosis,” the researchers wrote.
“We found that efficacy varied based on the location of the disease and choice of agent,” the team wrote, adding that Remicade was “the most common and effective … agent in various types of sarcoidosis.”
While adalimumab and etanercept showed relatively high success rates in extrapulmonary sarcoidosis, the data do not support using Simponi and Stelara in sarcoidosis.
“Although [TNF-alpha inhibitors] are the last option in treatment for some patients, they appear to be a practical and advantageous treatment option,” the researchers wrote.
Future appropriately controlled clinical trials, “using a standardized definition for objective treatment success,” are needed to confirm these findings, the team concluded.