This trial is evaluating whether Methotrexate will improve 1 primary outcome and 19 secondary outcomes in patients with Sarcoidosis. Measurement will happen over the course of 6 month scan.
This trial requires 194 total participants across 3 different treatment groups
This trial involves 3 different treatments. Methotrexate is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 3 and have had some early promising results.
A total of 5,850 cases per year are diagnosed in the US. Half of these cases are diagnosed between the age of 30 and 60. People who are diagnosed with sarcoidosis are more likely to have more than one family member with the disease.\n
Sarcoidosis is a complex disease, often affecting multiple organ systems. As the disease presents with multisystem involvement, signs and symptoms are often less clear-cut, and thus frequently unrecognized. Patients usually present with unexplained pulmonary involvement with or without involvement of the skin, lymph nodes, liver, or kidneys. Scleroderma-like skin changes are common and may be the first presenting sign. The most common skin lesions occur on the face, and include erythema nodosum and facial palsy. Patients often have fever and tender lymph nodes. The diagnosis can only be definitively established with skin biopsy. Patients usually have positive serology. Sarcoidosis is a diagnosis of exclusion.
Sarcoidosis can be divided into two subtypes: pulmonary sarcoidosis due to sarcoid crystals and extrapulmonary sarcoidosis (EPS) due to an unknown cause. The most common treatment is inhaled steroids in combination with steroids or, in cases of severe lung involvement, lung transplantation, which may be curative. Most patients have only one or two pulmonary infiltrates and thus respond to steroids alone. Sarcoid calcifications, if present, may respond to treatment with calcium blockers or surgery, which may be curative. EPS responds readily to steroids and calcification-inhibiting agents.
It is thought that exposure to certain fungi causes sarcoidosis, but whether this is the sole or a contributory cause is unclear. The use of inhaled corticosteroids or anticytokines (e.g. interferon) in sarcoidosis may increase the risk of chronic lung disease.
The standard of care is to treat patients with sarcoidosis until the disease becomes quiescent, and discontinuation of therapy is discouraged because of its possible risk of recurrence. Patients who have not demonstrated disease activity after 18 months of therapy are deemed to be quiescent. The success rate of spontaneous resolution in sarcoidosis is between 15-50%. Many patients remain asymptomatic and require no treatment. Patients who experience disease activity after spontaneous resolution are treated with corticosteroids to minimize or eliminate residual disease or to prevent recurrence. Treatment lasts as long as required, as the condition is often chronic and relapses may occur after a prolonged period of drug treatment.
Sarcoidosis is a chronic and systemic disease that commonly involves the lungs but also other organs such as the skin, lymph nodes, liver as well as the central nervous system. It has an important autoimmune component. The disease occurs about twice as often in women as in men but in both sexes, it causes fatigue and chronic cough and may cause painless, enlarging enlargements of the lymph nodes. It is commonly diagnosed in patients with tuberculosis who do not respond to or are resistant to anti-tuberculosis treatment. In some countries, sarcoidosis has a higher incidence in immigrants from certain Middle Eastern, South Asian and north African countries.
There has been limited research concerning the use of methotrexate. The evidence from the studies that have been carried out to date suggests that more research is needed before methotrexate can be recommended as the initial therapeutic agent.
A wide range of genetic and environmental factors likely combine to produce sarcoidosis. Genetic, epigenetic interactions and environmental factors, including occupational and hormonal exposures, likely contribute to sarcoidosis predisposition. Specific risk factors for certain sarcoids may be identified by genetic linkage studies or genome-wide association studies.
Use of methotrexate was found to be significantly more effective than the placebo in the treatment of lung sarcoidosis, in terms of lung function improvement, radiological appearance of the lung and quality of life.
Recent findings support the results obtained with 5-azacitidine, indicating that this agent may be the first choice of methotrexate for lepromatous leprosy-associated leprosy tuberculoid leprosy syndrome and also as a salvage therapy for refractory cases.
We have not been able to demonstrate evidence of an etiological contribution of genetic factors to the incidence of sarcoidosis, which suggests that sarcoidosis is acquired, possibly through an environmental trigger.
Treatment with MTX in addition to conventional corticosteroids seems to be an effective and safe treatment option for those with sarcoidosis whose disease responds to conventional therapies with corticosteroids alone. MTX-induced improvements in quality of life and respiratory function were sustained during long-term treatment, and in some cases, these improvements continued even at the completion of the long-term trial. Results from a recent paper indicate that MTX therapy should be explored as a first-line treatment for sarcoidosis. Additional trials are needed, but if confirmed in larger patient cohorts, this therapy may become a mainstay of sarcoidosis treatment.