Objectives: To evaluate the real-world effectiveness and laboratory impact of upadacitinib in patients with rheumatoid arthritis (RA) who had an inadequate response to at least one tumor necrosis factor inhibitor (TNFi), with a specific focus on clinical disease activity, inflammatory biomarkers, and metabolic indices.Methods: This single-center, retrospective, real-world study included 82 patients with RA who initiated upadacitinib (15 mg/day) following TNFi failure. Demographic data, disease characteristics, Disease Activity Score in 28 joints (DAS28-CRP), inflammatory markers (CRP and ESR), hematological indices, liver enzymes, and a comprehensive lipid profile were analyzed. In addition, the triglyceride–glucose (TyG) index and the HDL-to-monocyte ratio were calculated as markers of metabolic and cardiovascular risk. Clinical and laboratory parameters were compared between baseline and Week 12 using paired-sample statistical tests.Results: At Week 12, the DAS28-CRP score significantly decreased from 5.4 to 2.9 (p 0.001), with 80.5% of patients achieving low disease activity or remission. While total cholesterol, LDL-C, and HDL-C levels increased (all p 0.001), the HDL/monocyte ratio improved significantly by 7.7% (p = 0.012). A moderate negative correlation was observed between the change in DAS28-CRP and the change in HDL/monocyte ratio (rho = -0.42, p = 0.001). Creatine kinase (CK) levels showed a modest but statistically significant increase (+8.1%, p = 0.025); however, values remained within normal reference ranges and were not associated with muscular symptoms or treatment discontinuation. Clinical efficacy was consistent across rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) subgroups. No serious adverse events or treatment discontinuations due to adverse events were observed during the 12-week follow-up period.Conclusions: In this difficult-to-treat, real-world cohort of TNFi-refractory RA patients, upadacitinib demonstrated rapid and robust clinical effectiveness. Despite the anticipated elevations in lipid parameters, the concomitant increase in HDL cholesterol, the stable TyG index, and the marked suppression of systemic inflammation suggest no evident short-term deterioration in metabolic parameters. However, given the 12-week follow-up duration, these metabolic findings should be considered exploratory and hypothesis-generating rather than definitive regarding cardiovascular or metabolic safety. These results support upadacitinib as an effective therapeutic option for anti-TNF–resistant RA in routine clinical practice.
Akar et al. (Tue,) studied this question.