EULAR 2023—In a randomized, phase 2 clinical trial, more patients who received the investigational rheumatoid arthritis (RA) agent TLL-018 achieved 50% improvement in symptoms from baseline, measured by the ACR50 criteria, after 12 weeks of treatment than patients who received tofacitinib. Xiaong Zeng, MD, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China, presented these data during EULAR 2023, Milan, Italy, May 31–June 3.1
The study by Zeng et al. compared the efficacy of tofacitinib (Xeljanz) and TLL-018 in patients with active, moderate to severe RA who were intolerant to methotrexate and for whom methotrexate had proved inadequate.
Tofacitinib is a Janus kinase (JAK) inhibitor targeting mostly JAK-1, 2 and 3. TLL-018 is a highly selective, dual JAK1/tyrosine kinase (TYK) 2 inhibitor. Interleukin (IL) 12 and IL-23 are mediated by TYK.2 Therefore, a therapeutic agent that inhibits both JAK and TYK-2 may have the potential to be a more efficacious treatment than a single-mechanism agent.
Patients with RA were randomized in a 1:1:1:1 ratio to receive 10 mg, 20 mg or 30 mg of oral TLL-018 twice daily or 5 mg of oral tofacitinib twice daily. At week 12, patients were evaluated according to ACR50 criteria.
The study’s primary efficacy end point was the proportion of patients who achieved an ACR50 response by week 12. An ACR50 response is defined as a 50% improvement in tender and swollen joint counts and in three of the five additional criteria:
- Patient global assessment of disease activity;
- Physician global assessment of disease activity;
- Patient assessment of pain;
- Health Assessment Questionnaire; and
- C-reactive protein or erythrocyte sedimentation rate.
Patients who achieved an ACR50 response at week 12 continued the same treatment and dose through week 24.
Patients who did not achieve an ACR50 response at week 12 changed treatments. Patients who received tofacitinib and 10 mg of TLL-018 twice daily were switched to 20 mg of TLL-018 twice daily. Patients who received 20 mg of TLL-018 twice daily were switched to 30 mg of TLL-018 twice daily. Patients who received 30 mg of TLL-018 twice daily remained on 30 mg of TLL-018 twice daily.
The study’s secondary end points included the proportion of patients who achieved:
- A Disease Activity Score-28 for RA with CRP (DAS28-CRP) score of <2.6;
- An ACR20 and/or ACR70 response at all scheduled time points;
- An ACR50 response at scheduled time points, excluding week 12; and
- A Clinical Disease Activity Index (CDAI) for RA and other parameters at week 12.
All patients stopped treatment at week 24 and were followed for an additional four weeks. Safety was also assessed.