POS0861 EFFECT OF JAK1 INHIBITION ON EROSION REPAIR IN RHEUMATOID ARTHRITIS: A PILOT HR-PQCT STUDY

Background

Blockade of JAK, preferably JAK1, by upadacitinib is a feasible approach to achieve erosion repair as it 1) is approved for the treatment of rheumatoid arthritis (RA), 2) effectively controls the inflammation and 3) targets pathogenic pathways that influence local bone homeostasis in the joint.

Objectives

To evaluate whether inhibition of JAK1 could lead to erosion repair on high-resolution peripheral quantitative computer tomography (HR-pQCT) in patients with active RA.

Methods

This was a 24-week, single-centered, prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA (Disease activity score 28-C-reactive protein [DAS28-CRP] > 3.2) and ≥1 bone erosion on HR-pQCT. They were given upadacitinib 15mg once daily for 6 months. HR-pQCT of the 2-4 metacarpophalangeal (MCP) head was done at baseline and 6 months. The serum inflammatory cytokine profile and bone-cartilage interface biomarkers were also checked before and after treatment. The primary outcome was the change of erosion volume on HR-pQCT. Secondary outcomes included change in RA disease activity and serum biomarkers, as well as predictors of response to treatment. Erosion regression was defined as decrease in volume exceeding the smallest detectable change.

Results

The baseline clinical characteristics of the recruited patients were shown in Table 1. Of the 20 patients, 11 (55%) patients failed to respond to 3 or more csDMARDs. At 24-week, there was significant improvement in mean DAS28 (-1.75, p<0.001). Erosion regression was seen in 8 (40%) patients on HR-pQCT. Although no significant change in overall median erosion volume before and after upadacintinib (0.07 [-0.90-0.76mm3] mm3, p=0.904) was noted, the deterioration was less obvious compared to a historic cohort of 20 patients with similar age and disease activity on csDMARDs (median erosion volume change in 6 months: 0.67 mm3). There was significant reduction in the serum level of bone resorption marker C1M before and after treatment, which was not seen in the historic cohort. Significant reduction in various inflammatory cytokines (e.g. TNF-α, IL-6) was also noted after treatment. When patients were stratified according to whether or not they had failed multiple csDMARDs, significantly high proportion of patients in the non-multiple-DMARDs failure group had volume regression in at least one erosion compared to those in the failure group (75% vs 25%, p=0.04). There was improvement in mean total erosion volume in the non-failure group (-0.33±1.33 mm3), whereas mean erosion volume in the failure group worsened (2.09±7.62 mm3). One patient developed chest infection requiring hospitalization and withdrew from the study. No other serious adverse event was noted.

Conclusion

The results of the study suggested upadacitinib was clinically efficacious in refractory RA disease and could retard erosion progression. Regression of erosion was possible, particularly in those with limited csDMARDs exposure. Whether earlier JAK1 inhibition could lead to better structural outcome warrants further investigations.

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Acknowledgements:

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Disclosure of Interests

Ho SO Speakers bureau: Abbvie, Boehringer Ingelheim, Fosun Industrial, GSK, Janssen, Pfizer, Consultant of: Abbvie, GSK, Grant/research support from: Fosun Industrial, Isaac T. Cheng: None declared, Martin Li: None declared, Chun Kwok Wong: None declared, Lai-Shan Tam Consultant of: AbbVie, AstraZenaca, Boehringer Ingelheim, Eli Lilly, Janssen, Pfizer, and Sanofi, Grant/research support from: Amgen, Boehringer Ingelheim, GSK, Janssen, Novartis and Pfizer.