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Efficacy and safety of upadacitinib in patients with active psoriatic arthritis and axial involvement: results from two phase 3 studies

Arthritis Research & Therapy volume 25, Article number: 56 (2023), Baraliakos et al June 6, 2023, 9:57 a.m.

Presented By

Dr Walter Maksymowych MB ChB, FRCP(C), FACP
Chief Medical Officer, CARE Arthritis; Professor of Medicine, University of Alberta

Guest Commentary By:

Dr. Vinod Chandran MBBS, MD, DM, PhD, FRCPC
Associate Professor, Scientist, Krembil Research Institute

Synopsis

Introduction
  • Axial inflammation in psoriatic arthritis (axPsA) is an important phenotype that may affect as many as 70% of patients with PsA and is associated with higher disease activity and impairment of quality of life.
  • AxPsA may respond differently to therapeutics versus peripheral PsA
  • This post-hoc analysis assessed the impact of upadacitinib in patients with active PsA and axial involvement in the SELECT-PsA trials.
Methods
  • Patients with inadequate response or intolerance to ≥1 conventional synthetic DMARD (SELECT PsA-1) or ≥1 bio-DMARD (SELECT PsA-2) were randomized to upadacitinib 15mg or 30mg or placebo daily or adalimumab 40mg every other week for 24 weeks.
  • At 24 weeks placebo patients switched to upadacitinib 15mg or 30mg daily to week 56
  • Axial involvement was determined by investigator judgement (yes or no) based on the totality of available clinical information, lab investigations and imaging, if available.
  • Patients had to have BASDAI >4 and BASDAI item 2 (overall neck, back, or hip pain) >4 at baseline.
  • Efficacy outcomes included BASDAI, modified BASDAI excluding item 3 (peripheral pain), BASDAI 50 response, ASDAS, ASDAS <2.1 and <1.3, ASDAS MI response.
Results
  • 30.9% of PsA patients in SELECT-PsA 1 and 35.7% in SELECT-PsA 2 (bDMARD-IR) were defined as having axial involvement based on investigator judgement alone.
  • BASDAI and ASDAS score improvements were greater with upadacitinib 15 mg versus placebo at weeks 12 and 24 in both studies and according to both criteria used to define axial involvement.

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  • PsA patients treated with upadacitinib 15 mg showed consistent numerically higher responses than adalimumab across the efficacy endpoints regardless of the criteria used to define axial involvement.

Commentary

This post-hoc analysis convincingly demonstrates that upadacitinib has beneficial effects on axial symptoms in patients with axPsA. But does that mean a beneficial impact has been demonstrated in alleviating axial inflammation or are the observed effects a by-stander phenomenon in patients whose arthritis has improved to such a degree that patients are self-reporting improvements in a global manner in the non-specific BASDAI and ASDAS scores? There is no accepted case definition for axPsA but this will likely require imaging features, especially on MRI of the sacroiliac joints and/or spine. Clinical assessment of axial disease can be confused with degenerative spinal disorders because features of inflammatory back pain lack sensitivity and specificity for axial inflammation. Degenerative disorders are more frequent in the older demographic of PsA patients who develop axial inflammation. A more convincing case for the efficacy of treatment for axPsA can be made in trials selecting patients according to the presence of imaging features on MRI, especially a degree of inflammation in the sacroiliac joints and/or spine greater than would be expected in degenerative disorders. Moreover, it is essential to demonstrate improvement in the most objective parameter of axial inflammation, namely, bone marrow edema on MRI in the sacroiliac joints and/or spine.

Special Guest Commentary

A number of post hoc analyses of studies in PsA have been done to determine if axial disease also improves with the intervention. These analyses are hampered by a lack of validated case definition and non-specific outcome measures. The MAXIMISE study is the only study that attempted to specifically study axial PsA using MRI. However, the case definition was not validated and only around 60% of the patients had MRI changes (Baraliakos X, et al). Studies on axial PsA will be facilitated by MRI-based enrolment and response criteria in conjunction with clinical measures.

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