Speaking of tofacitinib, many people with rheumatoid arthritis may know.Tofatinib is the first FDA-approved JAK inhibitor for rheumatoid arthritis and the first FDA-approved oral antirheumatic drug to improve the condition in 10 years.
In addition, tofacitinib has great potential and is approved for the treatment of ulcerative colitis in addition to rheumatoid arthritis.In addition, the indications for psoriasis and psoriatic arthritis are also in the approval stage.Recently, researchers at Yale University found that tofacitinib can also be used to treat "disfiguring" sarcoidosis.
Speaking of sarcoidosis, many people may not understand it.But specifically speaking, thyroid nodules, pulmonary nodules, breast nodules, may be more clear to everyone.Sarcoidosis is an inflammatory disease that may affect multiple organs.Some patients can heal themselves without treatment, but there are still some patients with lung, heart, lymph nodes, skin and other organ damage.It can also lead to what can be called "disfiguring" skin lesions.Like the picture below.
To date, scientists know very little about sarcoidosis.The exact cause of sarcoidosis is not known.Many scientists speculate that it may be an autoimmune disease associated with an abnormal immune response, but the cause of this response is uncertain.How sarcoidosis spreads from one part of the body to another is still under investigation.
In addition, because of its non-specific symptoms, such as cough, weight loss, rash, joint pain and swelling, palpitations, dyspnea, headache, or vision loss, these clinical manifestations may appear in many other diseases, and physicians have no way to accurately diagnose sarcoidosis.According to the study's author, Nkiruka Emeagwali, Yale University School of Medicine, it can only be alleviated by the use of anti-inflammatory drugs such as steroids or methotrexate.However, the researchers pointed out that neither method has reliable results, and both can cause serious side effects.
A disease that is so intractable does require a powerful weapon to deal with, but how did tofacitinib, a classic drug for rheumatoid arthritis, get abducted by scientists to the "ship" of sarcoidosis?
The story starts in 2017.At that time, an article was published in the Scientific Report. Researchers at the University of Nevada, Renault, based on data on microRNA and protein-coding gene expression in peripheral blood mononuclear cells (PBMC) from healthy controls, sarcoidosis patients, and refractory sarcoidosis patients, identified 46 microRNAs and 1559 genes that were differentially expressed in patients with sarcoidosis of varying severity (healthy controls → patients with uncomplicated sarcoidosis → patients with refractory sarcoidosis).By analyzing these dysregulated microRNA-mRNAs, the researchers demonstrated that Jak-STAT signaling plays a role in the pathogenesis of sarcoidosis.
This study inspired Dr. Brett King of Yale University.He made a bold attempt to treat cutaneous sarcoidosis with the rheumatoid arthritis drug tofacitinib.The researchers selected a 48-year-old woman with refractory cutaneous sarcoidosis who had a disease history of up to 8 years during which the patient had been treated with a variety of anti-inflammatory drugs, including oral steroids and methotrexate for eight years, without any symptomatic improvement.
In this trial, this woman received tofacitinib orally twice daily.After 10 months of treatment, the skin nodules almost disappeared.The researchers further evaluated the results of histological and immunohistochemical examination of patient skin samples before and after treatment, which could prove to achieve clinical and histological remission.In addition, the researchers also performed RNA sequencing of skin specimens.The results confirmed that Jak-STAT pathway is not activated while cutaneous sarcoidosis disappears.In addition, the researchers wrote in the paper: Inhibition of Jak-STAT pathway may be effective for other types of sarcoidosis.
This study pioneered a new idea for the treatment of sarcoidosis.Co-author Nkiruka Emeagwali stated that "it is planned to evaluate the activation of Jak-STAT pathway in the lung fluid and blood of more than 200 patients with pulmonary and multi-organ sarcoidosis, an important step in unraveling sarcoidosis that has been enigmatic for many years."
The Yale team is currently conducting new clinical trials to further validate these findings.The study author King said that if confirmed, this will be a major breakthrough for patients with sarcoidosis.It is understood that Dr. King also previously conducted Jak inhibitor therapy for the treatment of other refractory skin diseases including white peony, alopecia areata and eczema.
Original: Tofacitinib Treatment and Molecular Analysis of Cutaneous Sarcoidosis
Author: William Damsky, Durga Thakral