King, JN, King S, et al. Clinical safety of robenacoxib in feline osteoarthritis: results of a randomized, blinded, placebo-controlled clinical trial. J Feline Med Surg 2015 Jun 9; epub ahead of print: 1-11.
Significant progress has been made in evaluating and utilizing pharmaceuticals to alleviate acute and postoperative pain in cats, but far fewer safe, effective long-term options for cats in chronic pain have been scientifically evaluated. Many cats, including and especially those who are elderly and/or have chronic kidney disease (CKD), suffer from the pain and impaired mobility associated with degenerative joint disease (DJD), including osteoarthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most successful approved modalities utilized in relieving the pain of osteoarthritis in humans and dogs, because they have anti-inflammatory and analgesic effects. These medications are also frequently used to treat pain and inflammation associated with chronic DJD in felines, but fewer options exist and less is known about the long-term effects of these drugs, especially in cats with concurrent CKD. At this time there are no NSAIDs labeled in the USA for chronic use in cats, although meloxicam is registered in Europe for use in acute and chronic musculoskeletal pain and inflammation in this species.
Robenacoxib is a relatively new NSAID developed for cats and dogs. In the USA, robenacoxib is only labeled for use up to 3 days in the control of postoperative pain and inflammation associated with some surgeries in cats. In Europe this drug is registered for short-term use for pain and inflammation due to musculoskeletal disorders as well as postoperative pain in cats. This study was designed to evaluate the safety results of robenacoxib in a long-term clinical trial utilizing client-owned cats with osteoarthritis, including a subset of cats with CKD.
A total of 194 cats, 108 females and 86 males, all gonadectomized, were recruited from around the USA for this prospective, randomized, blinded clinical trial comparing robenacoxib with a placebo. Patients qualified for the study if they had been diagnosed with osteoarthritis (history of impaired mobility for a minimum of 12 weeks prior to inclusion, and radiographic evidence of osteoarthritis of the axial or appendicular skeleton within 2 weeks prior to enrollment); 67% of the cats were 12 years of age or older (range, 8 months to 19 years). Some patients had pre-existing endocrine disorders (hyperthyroidism, diabetes mellitus), cardiac murmurs, or CKD in addition to chronic osteoarthritis. The subset of patients with concurrent CKD comprised 40 cats with a urine specific gravity < 1.030 and serum creatinine > 1.6 mg/dl; these animals were assigned to IRIS (International Renal Interest Society) stages 2, 3, and 4 based on their serum creatinine concentration. Robenacoxib as 6 mg flavored tablets was administered to 95 patients at a dose of 1.0-2.4 mg/kg orally daily for 28 days; 99 cats received placebo orally daily, also for 28 days.
All animals received clinical examinations, radiographic evaluation, body weight measurement, and clinicopathologic screening (serum chemistries, complete blood count, and urinanalysis) 14 days prior to commencement of the study. At days 0, 14, and 28 of the study the physical examination and clinicopathologic screening were repeated. Owners were required to document dosing and any potential adverse effects in a daily diary, and to complete a questionnaire on days 0, 14, and 28. On day 42, owners received a follow-up telephone call to request an update on the cat’s condition.
During the study, the investigators received 102 reports of adverse effects involving 70 cats; 33 of the cats (48 reports) were in the placebo group, while 37 cats (54 reports) were in the robenacoxib group. Differences between the two groups were not statistically significant. The most common adverse effect was vomiting. Clinically serious adverse effects were documented in 8 reports from 8 cats who received robenacoxib and 13 reports from 10 cats in the placebo group. None of the cats died or was euthanized during the study period. There was no statistically significant change in body weight or clinicopathologic findings from baseline between the placebo and robenacoxib groups upon completion of the study. At the time of telephone follow-up 14 days after the end of the study, owners of 30 cats from each group reported abnormal findings in their pets, most of which involved complaints of osteoarthritis-associated pain and behavior-related changes such as stiffness, slow movement, reluctance to jump, and lethargy.
In the subset of 40 cats with pre-existing CKD (median age, 15 years), there were 21 cats in IRIS stage 2 assigned to the placebo group, 18 in IRIS stage 2 in the robenacoxib group, one in IRIS stage 3 in the placebo group, and 0 in the robenacoxib group. No cases in IRIS stage 4 were in the study. None of the CKD patients received specific treatment for CKD during the study or the follow-up period. In this subgroup, there was no significant change in body weight from baseline for either the placebo or robenacoxib groups. There was also no significant change in serum creatinine or serum urea nitrogen from baseline between the placebo and robenacoxib groups. Seven of the CKD cats treated with placebo and 6 who received robenacoxib had adverse events; of these, 3 in the placebo group and two in the robenacoxib group had a clinically serious adverse effect.
Results of this study demonstrated that robenacoxib, administered orally daily for one month to cats with chronic osteoarthritis, including those with CKD (IRIS stages 1, 2, and 3), was well tolerated with no clinically detected evidence of damage to the gastrointestinal tract, kidneys, or liver. There were no significant differences in the incidence or type of reported adverse effects between treatment groups, and less incidence of clinically serious adverse effects was found in the group receiving robenacoxib when compared to the placebo group. No differences were also found in any safety endpoints in cats with concurrent CKD. A future paper will report efficacy results of robenacoxib in the same study group. [PJS]
Gowan RA, Lingard AE, et al. Retrospective case-control study of the effects of long-term dosing with meloxicam on renal function in aged cats with degenerative joint disease. J Feline Med Surg 2011;13:752-61.
King JN, Hotz R, et al. Safety of oral robenacoxib in the cat. J Vet Pharmacol Ther 2012;35:290-300.