Pelubiprofen, a non-steroidal anti-inflammatory drug (NSAID) that is related structurally and pharmacologically to ibuprofen, is as effective as celecoxib for reducing pain and stiffness in moderate to severe rheumatoid arthritis (RA) but it has a less favorable gastrointestinal (GI) profile than the COX-2 selective NSAID, a head-to-head study indicates.
At the end of 6 weeks of treatment, the mean decrease in pain severity from baseline was 26.2 mm (range: 0.0-80.0 mm) in the pelubiprofen group compared with 21.2 mm (range minus 20.0-90.0 mm) in the celecoxib group, an indication that pelubiprofen is noninferior to celecoxib with regard to reduction in VAS pain severity.
Similarly, the median duration of morning stiffness was decreased by 0.0 minutes in both treatment groups, while the mean decrease in the total use of rescue medication was 1.38 in the pelubiprofen group and 0.71 in the celecoxib group (difference, 0.7, 97.5% CI minus 0.6-∞).
Both medications also reduced scores on the Korean Health Assessment Questionnaire by a mean of 0.2 in both groups (difference, 0.0, 97.5% CI minus 0.2-∞).
On the other hand, 31.2% of patients in the pelubiprofen group versus 20.6% of patients in the celecoxib group experienced an adverse drug reaction (ADRs).
The most common ADRs were abdominal pain, which was reported by 13% of patients in the pelubiprofen group compared with 2.9% in the celecoxib group (P=0.03).
The frequency of GI ADRs was also higher in the pelubiprofen group at 20.8% compared with 8.8% in the celecoxib group (P=0.045).
"Pelubiprofen is believed to cause fewer GI adverse events than traditional NSAIDs because it is a prodrug ... and it has selective effects on COX-2 activity," In Ah Choi, MD, , and colleagues observe.
"Therefore we expected pelubiprofen to be useful at relieving the symptoms of RA in patients at high risk of an adverse GI event, and pelubiprofen was found to be as effective as celecoxib at pain reduction and for relieving stiffness in RA patients [but] more patients in the pelubiprofen group experienced an ADR and the frequency of gastrointestinal ADRs was higher in the pelubiprofen group."
On randomization, patients had either moderate or severe arthritis, defined by a disease activity score of 28 (DAS 28) ≥3.2 and had to have worsened pain, defined as an increase in the pain VAS score of at least 10 mm or of a 20% increase from baseline during the washout period.
Mean duration of disease was between 90 to 100 months and patients had been taking a disease-modifying drug (DMARD) for at least 3 months.
They remained on their DMARD over the course of the study period, but low dose prednisolone (10 mg or less) a day was allowed over a period of 4 weeks.
Following enrollment, patients were randomized to either 30 mg of pelubiprofen, three times a day or to celecoxib, 200 mg, twice a day.
Rescue medication in the form of an acetaminophen extended-release 650 mg tablet was the only rescue medication allowed.
Overall, 66 patients in the pelubiprofen group and 64 patients in the celecoxib group completed the 6-week study.
As the authors discuss, pelubiprofen had been previously reported to be better tolerated than aceclofenac and have a lower risk of peptic ulcers, bleeding, and abdominal pain when used to treat back pain.
"However, in the present study, it was found to have a poorer GI safety profile than celecoxib in patients with RA in terms of numbers of GI events and in terms of numbers of systemic and overall AEs (adverse events), which were almost twice as frequent in the pelubiprofen group," investigators observe.
A limitation of the study was that it was too short to allow meaningful evaluation of the potential long-term AEs associated with pelubiprofen, especially cardiovascular events.
Nevertheless, the authors concluded that results of their 6-week trial suggest that both drugs are effective and sufficiently safe to use in patients with moderate to severe RA.
Disclosures
There was no funding source for the study.
None of the authors declared they had any competing interests.
Primary Source
BMS Musculoskeletal Disorders
Choi, et al "Comparison of the efficacy and safety profiles of a pelubiprofen versus celecoxib in patients with rheumatoid arthritis: a 6-week, multicenter, randomized, double-blind, phase II, non-inferiority clinical trial" BMC Musculoskel Disorders 2014; DOI: 10.1186/1471-2474-15-375.