In November 2005, domestic recombinant human type II tumor necrosis factor receptor-antibody fusion protein for injection (Etanercept) was listed as a biological agent formally applied to the treatment of rheumatoid arthritis and ankylosing spondylitis, and it has been nearly three years since then. The clinical evaluation of this drug has also become relatively comprehensive. The adverse reactions of two rheumatoid arthritis patients hospitalized in the Department of Rheumatology of our hospital from December 2007 to March 2008 after the application of Isapro are now reported. 1. Clinical data Case 1, Zhao Mou, female, 29 years old, hospitalization number 144630. suffered from rheumatoid arthritis for 4 years, in the past 2 years due to non-standardized treatment led to the aggravation of the condition, the emergence of both hands proximal phalangeal joints, metacarpophalangeal joints part of the joints ulnar deformity, as well as swelling and pain in the two wrists, knees and ankles. The patient’s digestive system was poorly functioning, with a small diet and acidity when eating sweets. Barium meal fluoroscopy of the digestive tract showed retention of fluid in the stomach with tachycardia of the small intestine. She had paroxysmal tachycardia (about once a day), with a heart rate of 90~110 beats/minute, especially palpitations after waking up at night, and no abnormality was found in the electrocardiogram and cardiac supermarket. After admission to the hospital, the patient was first treated with oral Medrol (methylprednisolone) 12mg/d, Ai Ruohua (Leflunomide) 10mg/d, Torch Root Tablet 3 Tid, Futalin (diclofenac sodium) 75mg/d, Omeprazole 40mg/d, Betalucil 6.25mg Bid, drugs for improving bone metabolism, static drop of heat-clearing and detoxifying traditional Chinese medicines as well as oral herbal tonics for 3 weeks. After 3 weeks of treatment, the patient’s joint swelling and pain was significantly relieved, her diet was improved to normal, and the number of palpitations was significantly reduced, with palpitations occurring once every few days, and the symptoms were mild, the duration was shortened, and the heart rate was generally 80-90 beats/minute. In order to withdraw and reduce Medrol, the treatment regimen was adjusted to Medrol 8mg/d, and the rest of the regimen remained unchanged, and at the same time, subcutaneous injection of Isapro 25mg twice a week (i.e., 50mg/week) was administered for one week. After one week, the dosage of Medrol was reduced to 4mg/d, and the rest of the regimen was the same as before for 3 weeks. After that, Medrol was stopped, and the patient was treated with Ezetimibe (changed to 25mg/week due to intolerance of Ezetimibe adverse effects) and other oral regimens for 3 weeks. 3 weeks later, the patient’s adverse effects still persisted, and Ezetimibe was finally adjusted to 25mg once every 10 days. However, the adverse effects did not completely resolve. The patient had symptoms of the digestive and cardiovascular systems prior to the application of Ezetimibe, but after 3 weeks of comprehensive treatment at the time of admission to the hospital, the symptoms were significantly improved. After the first application of Ezetimibe (50mg/week), the patient reported generalized weakness, stomach discomfort, nausea without vomiting, palpitations, and increased heart rate of 100-110 beats/min, accompanied by nervousness, irritability, and a feeling of depression in the heart.The symptoms subsided after 3-4 days, but were then repeated due to the second administration within a week. After changing to 25mg/week, the patient’s gastrointestinal symptoms were relieved, but cardiac symptoms persisted, with palpitations, irritability, and nocturnal awakenings most noticeable within 24 hours of dosing, and the symptoms were largely relieved after 3 to 4 days. When the drug was changed to 25mg once every 10 days, the adverse reactions were still dominated by cardiac symptoms within 24 hours after the drug was administered, but the symptoms were generally relieved after 2 days. Case 2, Li, female, 55 years old, hospitalization number 144419. suffered from rheumatoid arthritis for 10 years. She was admitted to the hospital with a relapse of the disease due to an episodic infection and generalized swelling and pain in large and small joints. Treatment program to be oral prednisone 10mg / d, Ai Ruohua 20mg / d, methotrexate 7.5mg / week, torch flower root tablets 5 Bid, improve bone metabolism drugs, static drops of heat and detoxification of proprietary Chinese medicines, as well as oral Chinese herbal medicine soup comprehensive treatment for 2 weeks, joint swelling and pain significantly relieved. The patient asked to stop using prednisone for fear of hormonal side effects and use Ezetimibe for treatment. The regimen was adjusted to Ezetimibe 25mg twice a week (i.e., 50mg/week) subcutaneous injection, hormones were stopped, and the rest of the oral regimen remained unchanged. In the afternoon of the first injection, the patient experienced dizziness and dizziness, a hazy and confused feeling in the brain, and the next day, she had her menstrual period, which lasted for six days, was heavier than that of premenopausal period, and was lighter in color. The patient had been menopausal for 8 years. However, after 3 days of application of Ezetimibe, she felt that her joint symptoms had decreased. She continued to use ISAP for 8 weeks (50mg/week), and no similar phenomenon occurred, and the joint swelling and pain basically disappeared. Discussion In Case 1, the patient had upper gastrointestinal and cardiac symptoms, which were aggravated by the application of Ezetimibe, and the adverse reactions were reduced or alleviated after increasing the interval between two doses, which indicates that the adverse reactions are still related to this drug. However, we have observed this phenomenon many times when applying different drugs in the clinic, some patients usually have a certain system dysfunction, and then the adverse effects of the drug often show consistency with the dysfunction of the system. For example, the patient in this case, usually the upper gastrointestinal tract function is poor, the application of ISAP is likely to lead to aggravation of gastrointestinal symptoms. However, this is only an observation in the clinic, and the correlation needs to be demonstrated and investigated in future large-sample observations. In case 2, it is difficult to analyze the reason for the patient’s menstrual recurrence, and it cannot be denied that there is no adverse effect of ISAPP, but it is only speculation based on the phenomenon. It needs to be deeply studied in the future observation of large samples. The above two cases of adverse reactions after the application of ISP are outside the scope of the original adverse reactions of the drug, and are hereby included for the reference of clinical workers.