Daytime-only NSAID dosing may foster improved healing, recovery
MAUI, Hawaii — Administering NSAIDs only during the daily activity period may result in improved healing and postoperative recovery, while administering NSAIDs at night could significantly reduce their efficacy or inhibit healing, according to presenters at the 2020 Rheumatology Winter Clinical Symposium.
“I think chronotherapy of non-steroidals is incredibly interesting and actually quite important,” Arthur Kavanaugh, MD, professor of medicine at the University of California San Diego, told attendees during the opening presentation. “There is a circadian rhythm involved with these responses, and we know that inflammation and healing are just two parts of the same coin.”
In a recent murine study published in Scientific Reports, Al-Waeli and colleagues found that limiting NSAID treatment to the active phase of the circadian rhythm resulted in overexpression of circadian clock genes, and increased serum levels of anti-inflammatory cytokines IL-13, IL-4 and vascular endothelial growth factor. Likewise, the researchers also determined that NSAID treatments delivered during the resting phase resulted in severe bone healing impairment.
“[The researchers] found that if you timed a non-steroidal during their active period, you got an inflammatory effect as assessed by decreased pain, and you got less inhibition of bone healing,” Kavanaugh said. “If you did the opposite, treating them during the resting period with a non-steroidal, you didn’t get as much relief of pain and you interfered with bone healing.”
Although demonstrated in a murine model, Kavanaugh was quick to point out that there is a precedent for daytime-only dosing of prednisone, in order to reduce gastrointestinal toxicity and encourage mucosal healing.
“We already do this with prednisone, yet not with other short-acting medicines necessarily,” Kavanaugh said. “With this information in mind, should we be dosing our non-steroidals?”
“I think there is a circadian rhythm involved with all of this,” Jack Cush, MD, professor of medicine at University of Texas Southwestern Medical School, told attendees. “We have some patients who dose at night, which I think is a bad idea, unless they are having night pain, but then they are exposed to additional GI toxicity.”
Cush noted that although mice models have certain limitations — for instance, non-steroidals in mice are disease-modifying — “given all the major advances in medicine that started out in mice and have been extrapolated to humans, I think this is important. It speaks importantly to dosing during our active period and not during our resting period until you know otherwise. Obviously, there are GI considerations which is enough of a scientific reason to do it.”– by Robert Stott
Al-Waeli H et al. Sci Rep. 2020;doi:10.1038/s41598-019-57215-y.
Kavanaugh A. Cush J. Rheumatology 2019: Year in Review. New developments in Rheumatoid Arthritis. Presented at RWCS Annual Meeting; Feb. 12-15, 2020; Maui, Hawaii.
Disclosures: Cush reports investigator and/or consultant relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Horizon, Janssen, Pfizer and UCB. Kavanaugh reports investigator and/or consultant relationships with AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.