SAT0055 Baricitinib showed rapid and greater reduction in pain compared to adalimumab or placebo in patients with rheumatoid arthritis

Abstract

BackgroundA rapid and meaningful reduction in pain is important to quality of life in patients (pts) with rheumatoid arthritis (RA). Baricitinib (bari) is a selective inhibitor of Janus kinase (JAK)1/JAK 2 in development for pts with active RA.1ObjectivesTo evaluate the effect of bari treatment on pain reduction compared to adalimumab (ADA) or placebo (PBO) in pts with inadequate response to methotrexate (MTX) or biologic disease-modifying antirheumatic drugs (bDMARDs).MethodsIn RA-BEAM (NCT01710358), 1305 patients with inadequate response to MTX were randomised 3:3:2 to PBO QD, bari 4 mg once daily (QD), or ADA 40 mg biweekly.2 In RA-BEACON (NCT01721044), 527 pts with inadequate response or intolerance to bDMARDs were randomised 1:1:1 to PBO or bari (2 or 4 mg) QD.3 This post-hoc analysis reports the pts' assessment of pain using a visual analogue scale (VAS, range: 0 to 100 mm). The proportion of pts who achieved pain improvement of ≥30%, ≥50%, and ≥70% of their baseline pain at 1, 2, 4, 8, 12, 16, 20, and 24 weeks of treatment were compared between treatment groups using logistic models adjusted for geographic region, baseline pain score, baseline joint erosion status (RA-BEAM only), and history of bDMARD at screening (RA-BEACON only). Missing data were imputed using modified last observation carried forward.ResultsMean baseline pain scores were 60, 62, and 61 for PBO, bari 4 mg, and ADA, respectively, in RA-BEAM and 65, 62, and 66 for PBO, bari 2 mg, and bari 4 mg, respectively, in RA-BEACON. A significantly greater proportion of pts treated with bari 4 mg achieved ≥30% and ≥50% pain improvement as early as week 1 compared to PBO (both studies) and as early as week 4 compared to ADA (RA-BEAM) (Table). A significant pain improvement of ≥70% was achieved at week 12 for pts treated with bari 4 mg compared to PBO (both studies) and ADA (RA-BEAM). Pain improvement of ≥30%, ≥50%, and ≥70% with bari 2 mg was significant compared to PBO by week 12 (RA-BEACON). Significant improvements in pain for bari vs PBO and bari vs ADA were sustained through week 24.Table 1.Percent Pain Improvement in RA-BEAM and RA-BEACONRA-BEAMRA-BEACON PBOBari 4 mgADAPBOBari 2 mgBari 4 mg (N=488)(N=487)(N=330)(N=176)(N=174)(N=177) Pain Improvement ≥30% Week 12748***47***202532** Week 43767***†60***293850*** Week 124773***†64***3143*58*** Week 244974***69***3444*57***Pain Improvement ≥50% Week 11326***28***6917** Week 42248***‡37***1525*30*** Week 123157***†49***1731**35*** Week 243261***†52***2032**45***Pain Improvement ≥70% Week 1412***11***236 Week 4826***21***61114* Week 121437***‡28***719***18** Week 241641***‡32***922***29****p≤0.05 vs PBO; **p≤0.01 vs PBO; ***p≤0.001 vs PBO; †p≤0.05 vs ADA; ‡p≤0.01 vs ADA; p-values based on logistic regression model. ADA = adalimumab; Bari = baricitinib; PBO = placebo.ConclusionsBari-treated pts reported significantly greater and more rapid reductions in pain severity as measured by the pain VAS compared to PBO or ADA; improvements were sustained through 24 weeks. The results were similar regardless o...

Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double‐Blind, Randomized Controlled Trial

“…A significantly greater reduction in pain with another JAK inhibitor, baricitinib, in comparison to adalimumab has been reported, which was not solely explained by improvements in inflammation markers such as the CRP level, ESR, or SJC. This additional improvement may indicate an effect of JAK inhibition on central as well as peripheral mediators of pain, whereas TNF inhibitors mediate improvements in pain through reduction of peripheral inflammation . Although comparisons with adalimumab were not multiplicity‐controlled at all time points in this trial, significantly greater improvement in patients receiving upadacitinib compared to those receiving adalimumab were observed early, and were maintained through 6 months, for multiple measures of clinical response.…”

SAT0055 Baricitinib showed rapid and greater reduction in pain compared to adalimumab or placebo in patients with rheumatoid arthritis

“…Sex, smoking habit and high-resolution computed tomography (HRCT) pattern were not significantly different between two groups. Although there was no significant difference, more patients in AE group received methotrexate (MTX) treatment than those in non-AE group ( 3 This post-hoc analysis reports the pts' assessment of pain using a visual analogue scale (VAS, range: 0 to 100 mm). The proportion of pts who achieved pain improvement of ≥30%, ≥50%, and ≥70% of their baseline pain at 1, 2, 4, 8, 12, 16, 20, and 24 weeks of treatment were compared between treatment groups using logistic models adjusted for geographic region, baseline pain score, baseline joint erosion status (RA-BEAM only), and history of bDMARD at screening (RA-BEACON only).…”

Effect of upadacitinib on reducing pain in patients with active psoriatic arthritis or ankylosing spondylitis: post hoc analysis of three randomised clinical trials

“…Improvement in pain end points have been shown with biologic DMARDs (such as tumour necrosis factor inhibitors, including adalimumab, and interleukin-17A inhibitors) and, perhaps to an even greater extent, with JAK inhibitors in patients with AS, PsA and RA 19 20 29–31 43–45. Although pain in arthritis is predominantly secondary to inflammation, residual, non-inflammatory pain is also common and thought to be caused by joint damage or peripheral and central sensitisation of pain receptors 46.…”

“…Upadacitinib, a JAK inhibitor engineered for increased selectivity for JAK1 over JAK2, JAK3 and tyrosine kinase 2,24 has demonstrated efficacy and safety in patients with PsA in two phase III studies, SELECT-PsA 1 and 225 26 and in patients with active AS in a randomised phase II/III study, SELECT-AXIS 1 27 28. JAK inhibitors also demonstrated improvement in pain (inflammatory and other types) and physical function in rheumatoid arthritis (RA) studies 29–32…”