Monitoring for anti-drug antibodies may help improve sarcoidosis care
Study: Testing could prompt treatment changes, lead to better outcomes
People with sarcoidosis who respond poorly to tumor necrosis factor inhibitors (TNFi) — used to treat the immune system disease when other therapies haven’t worked — frequently develop anti-drug antibodies (ADAs), which are linked to lower blood drug levels and likely affect treatment effectiveness.
That’s according to a new study by U.S. researchers that “aimed to identify factors associated with TNFi … levels and ADA prevalence in real-world sarcoidosis patients.”
The team now suggests that more closely assessing individuals with sarcoidosis, with routine drug monitoring, could lead to better disease management for patients.
“Monitoring TNFi drug and ADA levels may aid clinicians in managing patients with a suboptimal response to therapy,” the researchers wrote, noting that, in their study, testing often prompted meaningful changes in treatment that improved outcomes.
The study, “Management of anti-drug antibodies against TNF-inhibitors in sarcoidosis patients,” was published in the journal Respiratory Medicine.
Corticosteroids remain the most widely used first-line treatment for sarcoidosis due to their effectiveness and rapid action. However, these medications are associated with serious side effects when used at high doses or over the long term.
For patients who cannot tolerate corticosteroids or do not respond to them, second- and third-line treatments that can help reduce corticosteroid use are often prescribed. Methotrexate, a type of cancer drug used at low doses to control inflammation, is one such second-line therapy.
TNF inhibitors are common third-line treatment for sarcoidosis
TNFi, which work by suppressing an immune signaling protein called TNF-alpha, are commonly used as third-line treatments. These include infliximab (sold as Remicade and available as biosimilars) and adalimumab (sold as Humira, with biosimilar drugs available). Although TNFi can be effective, many patients respond only partially or see the medication lose its benefits over time.
In other inflammatory diseases, this loss of response has often been associated with the development of anti-drug antibodies, or ADAs, which are immune system-generated antibodies that target a therapy and ultimately lead to low drug levels. In other conditions, this has prompted the use of routine drug monitoring. However, whether such an approach could be beneficial in sarcoidosis remains unclear.
To learn more, a team from the Medical University of South Carolina retrospectively analyzed data from 90 people with sarcoidosis who had been treated with TNFi and who underwent drug level testing after suboptimal clinical response.
All were followed at the university’s Susan Pearlstine Sarcoidosis Center of Excellence between August 2016 and October 2024.
Among them, 64 had received infliximab, generally at a dose of 5 mg/kg every six weeks, while 26 had been treated with adalimumab, most often at a dose of 40 mg once a week.
ADA testing was performed in nearly all patients — after a median of 23 months, or nearly two years, for those on infliximab, and after 11 months, or nearly one year, for those on adalimumab.
The antibodies were detected in about 1 in 5 people treated with infliximab (19%) and in nearly one-third of those on adalimumab (30.8%), according to the researchers.
A total of 8% of infliximab users also taking a second-line therapy developed ADAs. That compared with 39% of those on infliximab alone — reflecting an 87% lower risk of developing ADAs. No similar effect was seen in the adalimumab group.
Anti-drug antibodies can be ‘key contributor’ to poor treatment responses
In both groups, ADA formation was significantly linked to lower TNFi levels in the blood. Before the next dose, infliximab was not detected in the blood of patients who developed ADAs, but was present at a median of 16.4 micrograms per milliliter (mcg/mL) in those without antibodies. For adalimumab, patients with ADAs had a median drug level of 3.1 mcg/mL before the next dose compared with 14 mcg/mL in those without antibodies.
“This supports the conclusion that low … drug levels and ADA formation can be a key contributor to poor clinical response to TNFi therapy in sarcoidosis patients and should be considered by clinicians,” the researchers wrote.
However, because the study did not include TNFi responders and no ADA or drug level studies were done in such patients, the study can “not demonstrate that ADA formation is associated with nonresponse to TNFi in sarcoidosis,” the team added.
We hope our data and recommended management of patients with [anti-drug antibodies (ADAs)] will aid clinicians. … As the use of [tumor necrosis factor inhibitors] in sarcoidosis expands, recognition of and testing for ADAs as a potential complication is an important consideration for treating clinicians.
Of the 19 participants who developed ADAs, 10 were switched to a different TNFi within six months, with all but one experiencing a reduction in sarcoidosis symptoms and no signs of ADA formation. The remaining person had an infusion reaction to the new TNFi and was changed to a different class of third-line therapy, which effectively improved that patient’s condition.
Among those with ADAs and detectable drug levels, six continued on their original TNFi plus the addition or dose increase of second-line therapy. Still, most of them ultimately required a switch to a different TNFi or another third-line therapy.
The researchers recommended that all sarcoidosis patients on TNFi “also be on a second line agent for antibody prevention unless there are contraindications.”
“For patients with positive ADAs and undetectable drug levels, we recommend switching to a different TNFi or other third-line therapy,” the team wrote. “For those with positive ADAs who have detectable drug levels our data still support switching to a different [TNFi] agent.”
According to the researchers, this study of TNFi drug and ADA levels in sarcoidosis involved the largest known group of patients to date. The team wrote that they “hope our data and recommended management of patients with ADAs will aid clinicians and foster collaboration with larger, shared data sets that will continue to better inform management practices in sarcoidosis.”
In their conclusion, the researchers wrote that, “as the use of TNFi in sarcoidosis expands, recognition of and testing for ADAs as a potential complication is an important consideration for treating clinicians.”
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