Background/Purpose: Opioid use in RA patients has increased over the past 2 decades in the US. Little is known about the combined effects of opioids and disease-modifying antirheumatic drugs (DMARDs) on pain in RA. To assess pain reduction in opioid users and non-users, we tested the effect of 1) 4 mg baricitinib (BARI), an oral JAK1/JAK2 inhibitor, vs. placebo (PBO) with data pooled from Phase 3 trials, RA-BEAM (NCT01710358, with RA patients with an inadequate response [IR] to MTX), RA-BUILD (NCT01721057, with those with IR to conventional DMARDs), and RA-BEACON (NCT01721044, with those with IR to ≥1 tumor necrosis factor inhibitors), 2) BARI 2 mg vs. PBO in RA-BEACON, and 3) subcutaneous 40 mg adalimumab (ADA) every other week vs. PBO in RA-BEAM.

Methods: Opioid users were patients who reported opioid use during the trials. The number of opioid users/the total number of randomized patients were: 171/891 BARI 4 mg and 153/892 PBO in the pooled analysis, 54/174 BARI 2 mg and 58/176 PBO in RA-BEACON, and 34/330 ADA and 50/488 PBO in RA-BEAM. Pain was measured by the Patient’s Assessment of Pain visual analog scale (VAS, 0-100 mm). Last observation before treatment discontinuation or rescue was carried forward through Week 24. An ANCOVA model assessed differences in pain reduction at each time point between BARI 4 mg and PBO (pooled), BARI 2 mg and PBO (RA-BEACON), and ADA and PBO (RA-BEAM) by opioid users and non-users. Baseline pain VAS, age, BMI, and trial were covariates in the model. Heterogeneity of treatment effect (active vs. PBO) was evaluated across opioid users and non-users by interaction test. Analyses were not adjusted for multiplicity.

Results: BARI 4 mg had greater pain reduction vs. PBO in opioid users and non-users (P< 0.05) at all time points (Weeks 1, 2, 4, 8, 12, 14, 16, 20 and 24). Pain reduction in BARI 4 mg vs. PBO was similar between opioid users and non-users at all time points (interaction P >0.1 at all time points). At Week 24, the difference in pain VAS reduction between BARI 4 mg vs. PBO was -13.4 mm (95% CI: -19.0, -7.8) in opioid users and -14.3 mm (-16.7, -11.9) in non-users, interaction P=0.8. In RA-BEACON, BARI 2 mg had greater pain reduction vs. PBO in both opioid users and non-users (P< 0.05) starting at Week 12. Pain reduction with BARI 2 mg vs. PBO was similar between opioid users and non-users at all time points (interaction P >0.1 at all time points). At Week 24, the difference in pain VAS reduction between BARI 2 mg vs. PBO was -10.7 mm (-19.5, -1.9) in opioid users and -8.3 mm (-15.0, -1.6) in non-users, interaction P=0.8. In RA-BEAM, a significant difference in pain reduction was not observed for ADA vs. PBO in the opioid users; whereas, for non-users, a difference in pain reduction was observed for ADA vs. PBO at all time points (P< 0.05). At Week 24, the difference in pain VAS reduction between ADA vs. PBO was -4.9 mm (95% CI:-16.4, 6.6) in opioid users and -12.2 mm (-15.6, -8.9) in non-users, interaction P=0.2.

Conclusion: Pain reduction with BARI 4 mg was similar between opioid users and non-users and was observed at all time points. Pain reduction with BARI 2 mg vs. PBO was similar between opioid users and non-users from Week 12.  In contrast, ADA did not result in pain reduction compared to PBO in opioid users.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/baricitinib-4-mg-and-2-mg-once-daily-reduced-pain-in-both-patients-who-were-opioid-users-and-non-users-in-active-rheumatoid-arthritis-a-post-hoc-analysis-of-phase-3-trials/