This is a single-center, single-arm, prospective study on the efficacy and safety of Bortezomib in addition to standard therapy in patients with refractory rheumatoid arthritis.

Inclusion Criteria:

1. Age between 18~70 years.
2. Fulfilling the 2010 ACR/EULAR classification criteria for RA.
3. Failed to at least two bDMARDs (including but not limited to TNF inhibitors, IL-6 receptor inhibitors, T cell costimulation inhibitor and anti-B cell biologics) or tsDMARDs (including but not limited to JAK inhibitors) in combination with a csDMARD for at least 12 weeks. The dosage of cs/b/tsDMARDs needs to be stable for at least 6 weeks.
4. For patients receiving glucocorticoids, the dosage of GC needs to be less than or equal to 10mg prednisone equivalent and stable for at least 6 weeks.
5. For patients receiving non-steroid anti-inflammatory drugs, the dosage of NSAID needs to be stable for at least 2 weeks.
6. Neutrophil≥1.0×10^9/L, platelet≥100×10^9/L, alanine transaminase (ALT) and aspartate aminotransferase (AST) within 3 ULN, total bilirubin within 1.5 ULN.
7. Informed consent obtained.

Exclusion Criteria:

1. Other concomitant autoimmune diseases (except for Sjogren's syndrome secondary to rheumatoid arthritis).
2. The presence of severe uncontrolled cardiovascular, cerebrovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological or neuropsychiatric disorders, or abnormal laboratory tests. The investigators consider that participation in the study may make unacceptable risks to the subjects.
3. A history of malignancy with a clinical cure time of less than 5 years.
4. Pregnant or breast-feeding women, or planning to get pregnant or start breastfeeding during the study.
5. Vaccinated with live attenuated virus within 4 weeks before entering the study.
6. Allergic to bortezomib or mannitol.
7. Participated in any other investigational drug trial within 12 weeks before study initiation.
8. Active hepatitis or liver disease at the time of screening: Hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibodies (HCVAb) positive; (Note: If Hepatitis B Core Antibody, (HBcAb) is positive and HBsAg is negative, HBV-DNA detection will be performed, patient is eligible if HBV-DNA was negative).
9. Active herpes zoster infection, or severe infection requiring intravenous antibiotics or hospitalization occurred 12 weeks before study initiation.
10. Other conditions that not suitable for inclusion in the study, assessed by the investigators.