Bortezomib for the Treatment of Refractory Rheumatoid Arthritis

Study Overview
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Brief Summary
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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.

Official Title
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An Exploratory Clinical Study on Bortezomib for the Treatment of Refractory Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 70 years. Fulfilling the 2010 ACR/EULAR classification criteria for RA. 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. 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. For patients receiving non-steroid anti-inflammatory drugs, the dosage of NSAID needs to be stable for at least 2 weeks. 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. Informed consent obtained. Exclusion Criteria: Other concomitant autoimmune diseases (except for Sjogren's syndrome secondary to rheumatoid arthritis). 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. A history of malignancy with a clinical cure time of less than 5 years. Pregnant or breast-feeding women, or planning to get pregnant or start breastfeeding during the study. Vaccinated with live attenuated virus within 4 weeks before entering the study. Allergic to bortezomib or mannitol. Participated in any other investigational drug trial within 12 weeks before study initiation. 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). Active herpes zoster infection, or severe infection requiring intravenous antibiotics or hospitalization occurred 12 weeks before study initiation. Other conditions that not suitable for inclusion in the study, assessed by the investigators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bortezomib<br>bortezomib added on previous treatment | Drug: bortezomib<br>* bortezomib 2mg/week subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DAS28 remission or LDA at week 24 | Proportion of patients who achieve remission or low disease activity (LDA) at week 24 according to DAS 28. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DAS28 improvement at week 12 | Proportion of patients who achieve remission or low disease activity at week 12 according to DAS 28. Proportion of patients who achieve at least a 50% reduction of DAS28 at week 12. | 12 weeks | 
| SDAI improvement at week 12 and remission or LDA at week 24 | Proportions of patients who achieve remission or low disease activity at week 12 and week 24 according to SDAI. Proportion of patients who achieve at least a 50% reduction of SDAI at week 12. | 24 weeks | 
| CDAI improvement at week 12 and remission or LDA at week 24 | Proportions of patients who achieve remission or low disease activity at week 12 and week 24 according to CDAI. Proportion of patients who achieve at least a 50% reduction of CDAI at week 12. | 24 weeks | 
| ACR20, ACR50 and ACR70 at week 12 and week 24 | Proportions of patients who achieve ACR20, ACR50 and ACR70 at week 12 and week 24. | 24 weeks | 
| Changes in glucocorticoid dose | Changes in glucocorticoid dose at week 12 and 24 from baseline. | 24 weeks | 
| Adverse events during the study | All adverse events, severe adverse events and proportion of patients who discontinued bortezomib due to adverse events from the first dose of bortezomib to 4 weeks after the last dose. | 28 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bortezomib, rheumatoid arthritis