This study presents results of a clinical trial involving 1,281 patients and comparing the effects of upadacitinib, a selective and reversible Janus kinase inhibitor, with adalimumab, a tumor necrosis factor (TNF) inhibitor, and placebo. Direct effects on pain were assessed from patient global assessment of pain and tender joint count; in contrast, indirect effects were assessed from indicators of inflammation, such as itch, total enthesitis, Leeds enthesitis index and CRP.
The results indicate that direct and indirect effects of upadacitinib and adalimumab were both greater than that those of placebo and that upadacitinib causes greater pain reduction than does adalimumab in terms of total effects well as direct and indirect effects.
These findings are important because they indicate that the inclusion of a limited number of clinical outcome measures for both direct and indirect effects can illuminate the treatment response and help dissect the mode of action of DMARDs (disease modifying anti-rheumatic drugs). It will be of great interest to apply this approach to other agents used to treat PsA and determine whether direct and indirect effects always track together or whether some agents act predominantly or exclusively by either direct or indirect activity.
Importantly, this approach extends the usual focus on tender joint count to encompass signs and symptoms related to the skin (i.e., itch) and the entheses. In this regard, elucidating the effects of anti-inflammatory and immunosuppressive agents on nociplastic pain will be an intriguing direction of research to, hopefully, identify treatment approaches for this kind of pain.
9. MACE & VTE Risks
Abstract 0739: Merjanah et al.9
PsA, like other forms of inflammatory arthritis, is associated with an increased cardiac risk compared with that of the general population; this increase in risk could reflect the effects of inflammation, as well as the demographics of the population affected (e.g., features of the metabolic syndrome). Although atherosclerosis has an important contribution from inflammation, the effects of anti-inflammatory agents and DMARDs are complicated; agents may show similar benefits on inflammatory arthritis, but nevertheless differ in the effects on major adverse cardiovascular events (MACE) and venous thromboembolism (VTE).
In two nested case-control studies from a large MarketScan database, Merjanah and colleagues conducted analyses to determine any differences in the frequency of MACE and VTE in patients with either axial spondyloarthritis (axSpA) or PsA receiving a Janus kinase inhibitor or a TNF inhibitor or neither.
As the data indicate, the frequency of comorbidities in the population was high and included prior cardiovascular disease, obesity, diabetes and hypertension. Non-users of TNF inhibitors and Janus kinase inhibitors had greater odds of MACE relative to users of TNF inhibitors; further, in a comparison of Janus kinase inhibitors and TNF inhibitors, the odds of MACE were not increased. The odds for VTE among Janus kinase inhibitor users were increased, but this difference was not statistically significant.
