TY  - JOUR
A1  - Kremer, Joel M
A1  - Kivitz, Alan J
A1  - Simon-Campos, Jesus A
A1  - Nasonov, Evgeny L
A1  - Tony, Hans-Peter
A1  - Lee, Soo-Kon
A1  - Vlahos, Bonnie
A1  - Hammond, Constance
A1  - Bukowski, Jack
A1  - Li, Huihua
A1  - Schulman, Seth L
A1  - Raber, Susan
A1  - Zuckerman, Andrea
A1  - Isaacs, John D
T1  - Evaluation of the effect of tofacitinib on measured glomerular filtration rate in patients with active rheumatoid arthritis: results from a randomised controlled trial
JF  - Arthritis Research & Therapy
N2  - Introduction: 
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). During the clinical development programme, increases in mean serum creatinine (SCr) of approximately 0.07 mg/dL and 0.08 mg/dL were observed which plateaued early. This study assessed changes in measured glomerular filtration rate (mGFR) with tofacitinib relative to placebo in patients with active RA. 
Methods: 
This was a randomised, placebo-controlled, Phase 1 study (NCT01484561). Patients were aged \(\geq\)18 years with active RA. Patients were randomised 2: 1 to oral tofacitinib 10 mg twice daily (BID) in Period 1 then placebo BID in Period 2 (tofacitinib -> placebo); or oral placebo BID in both Periods (placebo. placebo). Change in mGFR was evaluated by iohexol serum clearance at four time points (run-in, pre-dose in Period 1, Period 1 end, and Period 2 end). The primary endpoint was the change in mGFR from baseline to Period 1 end. Secondary endpoints included: change in mGFR at other time points; change in estimated GFR (eGFR; Cockcroft-Gault equation) and SCr; efficacy; and safety. 
Results: 
148 patients were randomised to tofacitinib -> placebo (N = 97) or placebo -> placebo (N = 51). Baseline characteristics were similar between groups. A reduction of 8% (90% confidence interval [CI]: 2%, 14%) from baseline in adjusted geometric mean mGFR was observed during tofacitinib treatment in Period 1 vs placebo. During Period 2, mean mGFR returned towards baseline during placebo treatment, and there was no difference between the two treatment groups at the end of the study - ratio (tofacitinib -> placebo/placebo -> placebo) of adjusted geometric mean fold change of mGFR was 1.04 (90% CI: 0.97, 1.11). Post-hoc analyses, focussed on mGFR variability in placebo -> placebo patients, were consistent with this conclusion. At study end, similar results were observed for eGFR and SCr. Clinical efficacy and safety were consistent with prior studies. 
Conclusion: 
Increases in mean SCr and decreases in eGFR in tofacitinib-treated patients with RA may occur in parallel with decreases in mean mGFR; mGFR returned towards baseline after tofacitinib discontinuation, with no significant difference vs placebo, even after post-hoc analyses. Safety monitoring will continue in ongoing and future clinical studies and routine pharmacovigilance.
KW  - janus kinase inhibitor
KW  - renal function
KW  - CP-690,550
KW  - iohexol
KW  - disease comorbidities
KW  - plasma clearance
KW  - serum creatinine
KW  - kidney function
KW  - methotrexate
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143409
VL  - 17
IS  - 95
ER  -