Effect of tofacitinib on measured glomerular filtration rate in patients with active rheumatoid arthritis

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Effect of tofacitinib on measured glomerular filtration rate in patients with active rheumatoid arthritis
Key Take-Away: 

Tofacitinib is used for the treatment of rheumatoid arthritis. Changes in serum creatinine levels with the administration of tofacitinib have created a need to fully understand the impact of tofacitinib on renal function. That is why; authors in this study have evaluated its effect on glomerular filtration rate. 

Tofacitinib is an oral Janus kinase inhibitor for rheumatoid arthritis (RA) treatment. 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.

 

ABSTRACT: 
Background: 

Tofacitinib is an oral Janus kinase inhibitor for rheumatoid arthritis (RA) treatment. 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), involving patients 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: 

One forty eight patients were randomized 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.

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

Arthritis Research & Therapy 2015; 17:95
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