Are kidneys at risk? Serum creatinine levels in patients treated for active rheumatoid arthritis with tofacitinib

This study investigated creatinine levels in rheumatoid arthritis patients being treated with tofacitinib (Xeljanz, Jakvinus). It also examined whether there are increased kidney problems in these patients.

Creatinine is a chemical substance produced by the muscles. Measuring serum creatinine (creatinine in blood samples) is a simple test and is the most commonly used indicator of kidney function. Normal levels of creatinine are about 0.6 to 1.3 mg/dL for men and 0.5 to 1.1 mg/dL for women. Generally a rise in blood creatinine level indicates that the kidneys are not functioning properly.

Tofacitinib is a new drug approved for use in rheumatoid arthritis. During recent clinical trials it was found to increase the levels of serum creatinine without causing any clear kidney damage. 

This study examined results from 7 research studies. The serum creatinine levels and kidney-related adverse events from these studies were pooled and reanalyzed. Patients had mainly received either 5 mg or 10 mg of tofacitinib twice daily.

In the phase 3 trials, 3315 patients receiving tofacitinib had small average increases in serum creatinine levels compared to patients receiving a placebo (a substance that has no therapeutic effect, used for control in testing new drugs). The increases occurred mainly in the first 3 months of treatment

After 3 months patients receiving the 5 mg dose had a 0.07 mg/dL increase in creatinine and patients receiving the 10 mg dose had a 0.08 mg/dL increase in creatinine levels. After 3 months patients receiving the placebo had a 0.04 mg/dL increase in creatinine. During these first 3 months a greater than 30% increase in creatinine levels occurred in 1.4% of patients receiving the 5 mg dose and 1.9% of patients receiving the 10 mg dose.

Generally, elevations plateaued (leveled off) and remained within normal limits throughout the studies. However, 6 patients had creatinine levels above the maximum range (more than 1.3 mg/dL for men or more than 1.1 mg/dL for women). Two had received the 5 mg dose and 4 had received the 10 mg dose.

Patients who had higher levels of C-reactive protein (CRP, a protein marker indicating inflammation) before treatment had the biggest increases in serum creatinine.

When adverse events were investigated acute renal failure (acute kidney failure) occurred infrequently. Less than 0.01% of tofacitinib-treated patients had clinical acute renal failure. Acute renal failure was as a result of co-existing medical conditions including dehydration, widespread infection (sepsis), heart problems or multi-organ failure. Treating these conditions and a temporary or permanent break in tofacitinib treatment resolved the kidney problems and increases in creatinine.

The authors concluded that tofacitinib treatment was associated with small, reversible increases in serum creatinine that plateaued early. The mechanism behind these creatinine changes remain unknown.

This study was funded by Pfizer. Pfizer also developed and manufactured tofacitinib.