Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease

N Engl J Med 2023; 388:1966–1980 doi: 10.1056/NEJMoa2212728

Upadacitinib was associated with higher percentages of remission and endoscopic response regardless of previous failure of biologic therapy. This paper reports the Phase 3 efficacy and safety results of upadacitinib in patients with moderate-to-severe Crohn’s disease.

December 2023

This multicentre, retrospective study by Hayashi, et al. found no significant differences in efficacy and safety between tofacitinib, baricitinib, peficitinib and upadacitinib in patients with RA. Predictive factors for resistance to LDA achievement included baseline CRP and CDAI for tofacitinib and baseline glucocorticoid dose, baseline CDAI and number of previous b/tsDMARDs for baricitinib.

Rates of MACE and VTE events in patients with RA or PsA treated are consistent across 15 mg and 30 mg doses of upadacitinib, and comparable with active comparators adalimumab and MTX. Several risk factors were also identified for MACE and VTE events in patients with RA.

Rates of malignancy were similar between upadacitinib, adalimumab, and MTX. They were also consistent across RA, PsA, AS and nr-axSpA. A dose-dependent increased rate of NMSC was observed with upadacitinib in RA. For RA and PsA, being older (≥65 years) and male was associated with
an increased risk of malignancy excluding NMSC.

October 2023

Janus Kinase Inhibitor—Tofacitinib Associated with Pemphigus: An Analysis of the FDA Adverse Event Reporting System Data

ExpExpert Opin Drug Saf. 2023;22(12):1317–1320 doi: 10.1080/14740338.2023.2248872

This study presents initial data suggesting an association between the use of JAK inhibitors and pemphigus. This research used the FAERS database to investigate connections between JAK inhibitor usage and the occurrence of pemphigus as an adverse event.

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This study by Harrold, et al. showed that RA patients initiating upadacitinib reported improvements in RAPID3, pain, stiffness, and fatigue as early as Week 1, with 37.5% achieving RAPID3 LDA at Week 12. TNFi-experienced patients had similar outcomes.

In the UPJOINT open label study, the proportion of patients with PsA, and an inadequate response to csDMARDs or bDMARDs, who achieved minimal disease activity with upadacitinib was in line with the results of previous studies at 24 weeks. No new safety signals were identified.

The efficacy and safety of updacitinib in bDMARD-IR patients with AS were sustained through to one year in an open-label extension of the SELECT-AXIS 2 study.

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September 2023

Differential Properties of Janus Kinase Inhibitors in the Treatment of Immune-mediated Inflammatory Diseases

Rheumatology (Oxford) 2023;63(2):298–308 doi 10.1093/rheumatology/kead448

JAKis differ in structure, which affects their inhibitory concentration for different JAKs.

This review by Taylor, et al. compares the pharmacological profiles of JAKis, including abrocitinib, baricitinib, filgotinib, peficitinib, tofacitinib, and upadacitinib.

The results of a Bayesian network meta-analysis by Lee and Song showed that JAK inhibitors were more likely to achieve remission and LDA in DMARD-naive RA patients than MTX. However, there were no significant differences in remission rates nor LDA rates between the JAK inhibitors investigated.

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