Grapiprant: need to know

Grapiprant is a novel analgesic licensed for managing pain associated with osteoarthritis (OA) in dogs. It launched in the UK early 2019, having been available in the USA for nearly two years under the tradename Galliprant.

Grapiprant is an antagonist at a specific prostaglandin receptor, EP4, which is key in targeting pain. It belongs to a class of drugs called the piprants. In rat laboratory models grapiprant has been shown to reduce pain, inhibit paw swelling, reduce inflammatory biomarkers and synovial inflammation. We are familiar with the action of NSAIDs. As cyclo-oxygenase antagonists the NSAIDs prevent the production of a whole host of prostaglandins from arachidonic acid. Grapiprant works as a much lower level that the NSAIDs targeting that one specific receptor. Technically it is not a NSAID but must not be administered with NSAIDs. So lets take a look at some of the studies that are available on grapiprant.

A field study conducted on 285 dogs recruited cases where the vet had diagnosed arthritis. Dogs had clinical signs of OA and radiographic signs in one appendicular joint. A pain score was performed by the owner using the Canine Brief Pain Inventory (CBPI), a validated pain scale for OA, and the vet completed an assessment referred to as the total orthopaedic score (TOS) which evaluated factors such as lameness, range of motion and pain on palpation of the joint. The aim of the study was to document efficacy of 2mg/kg grapiprant SID per os and evaluate safety of the drug in a clinical population of dogs. Dogs recruited were split equally into treatment and control groups.

Dogs in this study were evaluated using the CBPI every 7 days for 28 days and day 0, 14 and 28 using the TOS. The outcome measure used to document success of treatment was pain severity score reduction of one point and pain interference score reduction of two points on the CBPI. Read more here about chronic pain scoring.

In the 262 dogs that completed the study and were evaluated for effectiveness, a statistically significant difference (p = 0.03) was demonstrated between the success rate in the grapiprant tablet group (48.1%) when compared to the control group (31.3%). Grapiprant treated dogs had a greater improvement in TOS than placebo (p < 0.08). Ten dogs in the control group and one in the grapiprant group were removed from the study due to lack of efficacy. The dose range of grapiprant was 1.5-2.9mg/kg due to the tablet size used. You may be looking at those placebo numbers. In a placebo controlled study it is normal to see a placebo response rate of approximately 20-30%. Interesting owner psychology!

In a separate study the long term safety of grapiprant at a variety of doses was evaluated over a period of 9 months. The investigators comment in their discussion ‘Only mild signs of gastrointestinal disturbance, such as occasional vomiting and soft or mucoid faeces that occasionally contained blood, were identified in dogs that received grapiprant. Control dogs also had these signs, albeit to a lesser extent than did the treated dogs. No dogs developed ulcers of the gastrointestinal mucosa.’ It should be noted that there is no direct comparison to a NSAID group at the present time so further work is required before we can conclude this. This study did look at a range of doses from 0-50mg/kg (licensed dose is 2mg/kg), so again, further work is required to fully document adverse effects seen at the commonly prescribed dose. This is where prescribers have a responsibility to report adverse effects to the pharmaceutical company to allow further evaluation in the post-license phase of a drug. Adverse events can be reported here.

Where is grapiprant likely to fit? Is this an analgesic for first line use before NSAIDs? Or would we use grapiprant in dogs where NSAIDs are less effective? Some of these questions remain to be answered. If considering grapiprant in the face of an ineffective NSAID response we should first ensure that we have used the NSAID for a reasonable period of time (4 weeks recommended). It is also advised to switch NSAIDs if response to one is less than expected. Read more here about choices in chronic pain analgesic options.

The main adverse effect seen with grapiprant appears to be vomiting, which in some cases resolves (and doesn't require cessation of treatment) but in some cases persists once therapy is withdrawn. If you see such a case it is really important to play your role and report this to the pharmacovigilance team at Elanco.

Due to the mechanism of action grapiprant is contraindicated with steroids and NSAIDs. In theory, there is no advantage to be gained regarding analgesia even if you did use it alongside NSAIDs. There's no reason why it shouldn't be used alongside paracetamol, which we don't consider an NSAID. Read about long term paracetamol use here.

What should you do during the preoperative period? Grapiprant does not have a license for perioperative pain, however should be effective for dealing with prostaglandin mediated pain in the surgical patient. You may be faced with this if you have a patient with OA being treated with grapiprant which then requires surgery for cruciate disease. My advice in these cases is to continue the SID dosing of grapiprant and avoid the use of NSAID perioperatively. If you feel that further analgesic options should be employed then of course we should be performing nerve blocks, could consider adding paracetamol and use either a ketamine CRI or bolus.

This post was written by Matt Gurney.

Matt & Carl established Zero Pain Philosophy to provide educational resources to veterinary professionals enabling optimal management of pain.

Matt Gurney is an RCVS & European Specialist in Veterinary Anaesthesia & Analgesia and works at Anderson Moores Veterinary Specialists. Matt is Vice-President of the European College of Veterinary Anaesthesia & Analgesia.

Carl Bradbrook is an RCVS & European Specialist in Veterinary Anaesthesia & Analgesia and is President of the Association of Veterinary Anaesthetists. Carl works at Anderson Moores Veterinary Specialists.