Efficacy and Safety of Telitacicept in the Treatment of Refractory Rheumatoid Arthritis

The refractory rheumatoid arthritis is a heterogeneous subgroup of RA patients, whose disease has not been satisfactorily controlled with several lines of DMARDs using the treat-to-target strategy. In 2024, telitacicept was approved for the treatment of rheumatoid arthritis in China, and several case reports have demonstrated its efficacy in refractory RA.

This study plans to enroll 420 adult patients with difficult-to-treat rheumatoid arthritis, randomized in a 1:1 ratio to receive either telitacicept (160mg qw) plus standard therapy or standard therapy alone for 24 weeks.

• Telitacicept 160mg (Biological): Telitacicept 160 mg will be administered subcutaneously once weekly for 24 consecutive weeks.
• Standard therapy (Drug): Standard therapy includes DMARDs, GCs, and NSAIDs.

Primary outcomes

• ACR20 response rate [Week 24]

Secondary outcomes

• ACR50 and ACR70 response rates [Week 24]
• Change from baseline in SDAI [Week 24]
• The proportion of subjects achieving SDAI ≤ 3.3 [Week 24]
• Change from baseline in CDAI [Week 24]
• The proportion of subjects achieving CDAI ≤ 2.8 [Week 24]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Male and Female participants of age >18 years will be enrolled;
2. Meet the 2021 EULAR criteria for the diagnosis of difficult-to-treat rheumatoid arthritis;
3. The dose of prednisone should be ≤10 mg or equivalent dose of corticosteroids, and the dose must remain unchanged for at least 4 weeks;
4. Consent to use effective contraception during the study period (women of childbearing age);
5. Voluntarily signed informed consent.

Exclusion Criteria:

1. Those with specific allergy history (asthma, urticaria, eczema, etc.), or allergic constitution, or hypersensitivity to any component of telitacicept;
2. Subjects who have received intra-articular, intravenous, intramuscular, or intrarectal (excluding suppositories for anal diseases) corticosteroids within 4 weeks prior to baseline;
3. Subjects who have used Tripterygium wilfordii glycosides, total glucosides of paeony, Huobahuagen tablets, or other immunosuppressive or anti-inflammatory traditional Chinese medicines or decoctions within 4 weeks prior to baseline;
4. Subjects currently using non-steroidal anti-inflammatory drugs (excluding acetaminophen) whose dose has not been stable for 4 weeks prior to randomization, or who are unable to continue treatment at the original dose during the trial;
5. Subjects with abnormal laboratory parameters, including but not limited to the following:

   * White blood cell count < 2.0 × 10⁹/L;
   * Neutrophils < 1.0 × 10⁹/L;
   * Hemoglobin < 80 g/L;
   * Platelet count < 50 × 10⁹/L;
   * Serum creatinine > 2 × ULN or creatinine clearance (CCr) ≤ 50 mL/min
   * Total bilirubin > 2 × ULN, ALT > 3 × ULN, AST > 3 × ULN, alkaline phosphatase > 2 × ULN;
6. Female subjects who are pregnant or breastfeeding;
7. Those with other systemic inflammatory diseases other than RA (excluding secondary Sjögren's syndrome), including but not limited to juvenile chronic arthritis, Crohn's disease, ulcerative colitis, psoriatic arthritis, systemic lupus erythematosus, ankylosing spondylitis, reactive arthropathy, systemic vasculitis, or gout;
8. Those with non-inflammatory refractory arthritis (NIRRA) (few or no swollen joints, normal CRP concentration, non-erosive pathology);
9. Subjects who test positive for any one or more of the following: hepatitis B surface antigen, hepatitis C virus antibody, syphilis-specific antibody, or human immunodeficiency virus antibody;
10. Subjects with active infection at screening, or who have had an infection requiring systemic treatment within 1 month prior to screening, or who are at high risk of infection;
11. Subjects with clinical, radiological, or laboratory evidence of active tuberculosis at screening;
12. Subjects with clinically significant cardiovascular, respiratory, digestive, endocrine, hematologic, neurological, or psychiatric disorders, or any other serious and/or unstable disease or history thereof, that in the investigator's opinion would pose a safety risk if participating in this study;
13. Subjects with other primary malignancies;
14. Subjects with a history of herpes zoster, major cardiovascular events, thromboembolism, or lymphoproliferative disease;
15. Investigator considers candidates not appropriating for the study.

• Results publication: Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, Keystone EC, Loveless JE, Burmester GR, Cravets MW, Hessey EW, Shaw T, Totoritis MC; REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006 Sep;54(9):2793-806. doi: 10.1002/art.22025. PMID 16947627
• Results publication: Tao Y, Zhang J, Li H, Zhou J, Wu M. Clinical efficacy and safety of telitacicept combined with methotrexate in the treatment of rheumatoid arthritis. Am J Transl Res. 2026 Apr 15;18(4):3220-3229. doi: 10.62347/PKWI2684. eCollection 2026. PMID 42170450
• Results publication: Hofman ZLM, Roodenrijs NMT, Nikiphorou E, Kent AL, Nagy G, Welsing PMJ, van Laar JM. Difficult-to-treat rheumatoid arthritis: what have we learned and what do we still need to learn? Rheumatology (Oxford). 2025 Jan 1;64(1):65-73. doi: 10.1093/rheumatology/keae544. PMID 39383505