The Impact of Baseline Pain Intensity on the Analgesic Efficacy of Ibuprofen/Caffeine in Patients with Acute Postoperative Dental Pain: Post Hoc Subgroup Analysis of a Randomised Controlled Trial

• Published in: Advances in therapy Vol. 37; no. 6; pp. 2976 - 2987
• Main Authors: Förderreuther, Stefanie, Lampert, Anette, Hitier, Simon, Lange, Robert, Weiser, Thomas
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.06.2020
• Subjects: Acute Pain - drug therapy; Adolescent; Adult; Analgesics - administration & dosage; Analgesics - therapeutic use; Caffeine - administration & dosage; Caffeine - therapeutic use; Cardiology; Dose-Response Relationship, Drug; Double-Blind Method; Endocrinology; Female; Humans; Ibuprofen - administration & dosage; Ibuprofen - therapeutic use; Internal Medicine; Male; Medicine; Medicine & Public Health; NCT; NCT01929031; Oncology; Original Research; Pain Management - methods; Pain, Postoperative - drug therapy; Pharmacology/Toxicology; Rheumatology; Tooth, Impacted - surgery; Young Adult; Analgesia; Postoperative pain; Dental pain; Fixed-dose combination; Ibuprofen; Caffeine
• ISSN: 0741-238X; 1865-8652; 1865-8652
• DOI: 10.1007/s12325-020-01297-y

Introduction A fixed dose combination (FDC) of ibuprofen 400 mg and caffeine 100 mg has been shown to be more effective than ibuprofen 400 mg alone for the treatment of acute postoperative dental pain in a phase III randomised controlled trial. A post hoc subgroup analysis of the primary data from an active-/placebo-controlled, double-blind, single-centre, parallel-group study was conducted in patients with moderate or severe baseline pain. Methods After dental surgery, patients with moderate or severe pain, which was determined on a 4-point verbal rating scale (‘no pain’ to ‘severe pain’), received a single dose of ibuprofen 400 mg/caffeine 100 mg FDC, ibuprofen 400 mg, caffeine 100 mg or placebo. Pain relief (PAR) and pain intensity were assessed 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7 and 8 h after administration of study medication. The primary study endpoint was the time-weighted sum of PAR and pain intensity difference (PID) from pre-dose baseline, summed for all post-dose assessment times from 0 to 8 h (SPRID 0–8h ). Results There were 237 patients with moderate pain and 325 with severe pain at baseline. SPRID 0–8h was significantly improved with the FDC versus ibuprofen, caffeine and placebo in the moderate and severe pain subgroups. Adjusted mean SPRID 0–8h difference for the FDC versus ibuprofen was 18.19 ( p  < 0.0001) for patients with moderate pain and 7.70 ( p  = 0.0409) for patients with severe pain. With the exception of the 7-h measurement in patients with moderate pain, PID was significantly improved with the FDC versus ibuprofen at all measured time points from 0.5 to 8 h. In the severe pain subgroup, PID was significantly improved for the FDC versus ibuprofen from 0.5 to 3 h post-dose, but was not significantly different thereafter. Conclusion The enhanced analgesic efficacy of ibuprofen/caffeine FDC versus ibuprofen is most pronounced in patients with moderate intensity pain at baseline, and also evident in patients with severe baseline pain. Trial Registration ClinicalTrials.gov identifier, NCT01929031. Plain Language Summary The non-steroidal anti-inflammatory drug (NSAID) ibuprofen is commonly used to relieve mild to moderate pain. Research suggests that combining ibuprofen with caffeine can increase the analgesic efficacy. Previously, a randomised, double-blind, placebo-controlled study showed that this ibuprofen/caffeine combination was significantly more effective than ibuprofen alone for relieving pain after dental surgery (wisdom tooth removal). Patients in that study had moderate or severe pain, so the researchers conducted another analysis of the study data to investigate how well the ibuprofen/caffeine combination worked in patients with moderate pain and in patients with severe pain. The study found that a single dose of ibuprofen/caffeine was significantly more effective than ibuprofen alone in patients with moderate pain and in those with severe pain. The analgesic effects of ibuprofen/caffeine were more marked in patients with moderate pain than in those with severe pain. This indicates that ibuprofen/caffeine is an effective pain reliever for patients with moderate pain, and to a lesser extent in patients with severe pain.