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Arthritis Res Ther. 2015 Apr 6;17:95. doi: 10.1186/s13075-015-0612-7.

Evaluation of the effect of tofacitinib on measured glomerular filtration rate in patients with active rheumatoid arthritis: results from a randomised controlled trial.

Author information

1
Albany Medical College and The Center for Rheumatology, Albany, NY, USA. jkremer@joint-docs.com.
2
Altoona Center for Clinical Research, Duncansville, PA, USA. ajkivitz@yahoo.com.
3
Hospital CEM/BIOCEM, Merida, Mexico. jabrahamsimon@yahoo.com.mx.
4
Nasonova State Institute of Rheumatology, Moscow, Russia. nasonov@irramn.ru.
5
University Hospital Würzburg, Würzburg, Germany. Tony_H@ukw.de.
6
Yonsei University College of Medicine, Seoul, South Korea. SOOKONLEE@yuhs.ac.
7
Pfizer Inc, Collegeville, PA, USA. bonnie.vlahos@pfizer.com.
8
Pfizer Inc, Collegeville, PA, USA. connie.hammond@pfizer.com.
9
Pfizer Inc, Collegeville, PA, USA. JACK.BUKOWSKI@PFIZER.COM.
10
Pfizer Inc, Collegeville, PA, USA. Huihua.Li@pfizer.com.
11
Pfizer Inc, Collegeville, PA, USA. seth.schulman@pfizer.com.
12
Pfizer Inc, San Diego, CA, USA. susan.raber@pfizer.com.
13
Pfizer Inc, Groton, CT, USA. andrea.zuckerman@pfizer.com.
14
National Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle-upon-Tyne, UK. John.Isaacs@newcastle.ac.uk.

Abstract

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 ≥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.

TRIAL REGISTRATION:

Clinicaltrials.gov NCT01484561. Registered 30 November 2011.

PMID:
25889308
PMCID:
PMC4445792
DOI:
10.1186/s13075-015-0612-7
[Indexed for MEDLINE]
Free PMC Article
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