Pharmacokinetics and safety of the combination of KL130008 and methotrexate in rheumatoid arthritis patients: a multicenter, open-label phase Ib trial.

The combination of the JAK1/2 inhibitor KL130008 with methotrexate (MTX) is expected to improve treatment outcomes in rheumatoid arthritis (RA). This study evaluated the pharmacokinetics and safety of this combination therapy. In an open-label, multicenter trial, 31 patients with RA received KL130008 combined with MTX. Pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax) were assessed and compared between combination and monotherapy. Safety was evaluated through treatment-emergent adverse events (TEAEs), laboratory tests, and ECGs. Primary endpoints were pharmacokinetic bioequivalence between combination and monotherapy. Secondary outcomes included safety and tolerability. Geometric mean ratios and 90% confidence intervals for key pharmacokinetic parameters of KL130008 and MTX were within the 80-125% bioequivalence range, indicating no significant interaction. A slight increase in 7-OH-methotrexate exposure was observed but deemed clinically insignificant. TEAEs related to KL130008 occurred in 71.0% of patients, with anemia (25.8%) and increased platelet count (12.9%) most common. All abnormal laboratory or ECG findings were mild. KL130008 combined with MTX demonstrated favorable pharmacokinetics and acceptable safety in RA patients. These findings support further investigation of this combination. Limitations include the open-label design and small sample size. This trial was registered with the Chinese Clinical Trial Register (ChiCTR2100050764) on 4 September 2021.