Commentary - (2025) Volume 0, Issue 0
Received: 06-Jun-2025, Manuscript No. IPACLR-25-15695; Editor assigned: 09-Jun-2025, Pre QC No. IPACLR-25-15695 (PQ); Reviewed: 23-Jun-2025, QC No. IPACLR-25-15695 ; Revised: 30-Jun-2025, Manuscript No. IPACLR-25-15695 (R); Published: 09-Jul-2025, DOI: 10.36648/2386-5180.25.13.S6.001
Psoriatic Arthritis (PsA) is a chronic, immune-mediated, inflammatory arthropathy that affects 6–41% of patients with psoriasis and has an overall prevalence of 0.2% in Europe. PsA is a clinically heterogeneous condition with musculoskeletal involvement, such as arthritis, dactylitis, enthesitis, axial involvement and skin and nail psoriasis. The impact of PsA on quality of life is similar to that of Rheumatoid Arthritis (RA) and is associated with an increased risk of cardiovascular comorbidities and increased mortality.
PsA treatment addresses not only all of the disease domains but also has to take into account previous and concomitant therapies, as well as associated comorbidities (i.e., cardiovascular disease, metabolic syndrome, liver disease, mood and anxiety disorders, chronic infections, malignancies and fibromyalgia) all of which increase its complexity.
Pharmacological treatment of PsA includes conventional synthetic Disease-modifying Antirheumatic Drugs (csDMARDs), a broad group of biologics DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) such as apremilast and Janus Kinase (JAK) inhibitors. Despite the availability of these treatments, the proportion of patients who achieve the target of Minimal Disease Activity (MDA) remains low. For example, in Randomized Clinical Trials (RCT) where Tumor Necrosis Factor (TNF) inhibitors were used to treat PsA patients, only 24 to 52% achieved MDA, with similar numbers observed in observational studies. Evidence from the EuroSpA, DANBIO and CORRONA registries, observations studies and clinical trials, shows that the American College of Rheumatology 70% improvement criteria (ACR70) responses and MDA are only achieved in 20% to 30% of PsA patients after 6 months or more months of treatment with bDMARDs therapy. This data highlights the need for additional therapeutic options beyond biological therapy.
It is known that a remarkable proportion of patients with this disease remain resistant to advanced therapeutic interventions and are labelled as Difficult-to-treat (D2T PsA.) Several factors may contribute to inadequate response to treatments in these patients. The truth is that currently there is no consensus to what constitutes active disease and how many drugs a patient must fail to be classified as D2T PsA.
In 2021 Upadacitinib (UPA)15 mg once daily was approved by the European Medicines Agency (EMA) for the treatment of active PsA in adult patients who have responded inadequately or are intolerant to one or more DMARDs, either as monotherapy or in combination with methotrexate. The approval was based on two RCTs of UPA in patients with refractory PsA to nonbiologic or biologic DMARDs (SELECT-PsA 1 and SELECT-PsA 2 trials), which demonstrated greater efficacy regarding musculoskeletal manifestations, psoriasis, physical function, pain and quality of life than placebo. Nevertheless, its real-world performance in difficult-to-treat PsA remains underexplored.
This observational, multicenter, open-label study evaluated the efficacy and safety of upadacitinib in 134 patients with psoriatic arthritis during a period of two years (97 women, mean age 51.8 ± 11.2 years, mean disease duration 9.94 ± 7.72 years) who showed inadequate response to advanced therapies. In addition, we aimed to compare the clinical profiles of patients from our cohort with those included in the SELECT-PsA 2 trial.
Enrolled patients displayed the following cardiovascular comorbidities: smoking (24,7%), obesity (26%), high blood pressure (20%) and type 2 diabetes mellitus (8%). Moreover, 2% of the patients had a history of heart failure and 2% had a history of deep vein thrombosis. The most common phenotype was peripheral PsA (n=83, 61.9%), followed by mixed PsA (n=41, 30.6%) (peripheral and axial PsA) and axial PsA (n=10, 7.5%). Most patients (74.6%) had received at least two biological/ targeted synthetic disease-modifying antirheumatic drugs with different mechanisms of action. UPA was initiated at 15 mg daily. Concomitant glucocorticoid therapy was administered to 58 patients (43.3%), with a mean prednisone dose of 8.3 ± 5.6 mg/d. UPA in combination with csDMARDs was used in 64 patients (47.8%): methotrexate (n=39), leflunomide (n=19) and sulfasalazine (n=10). Seventy patients (52.2%) received UPA monotherapy. The mean follow-up was 6.0 ± 5.1 months.
Rapid and sustained improvement in the disease activity indices (DAS28-ESR and DAPSA) was observed. The DAS28-ESR score decreased from a median (IQR) of 4.7 (3.97; 5.38) at baseline to 3.77 (2.87; 4.76) (p<0.001) in the first month and the DAPSA score decreased from a median of 25 (18.06; 30.60) to 17 (10.10; 22.60) (p<0.001). Improvements were also observed in patients with axial, skin and nail involvement and those with enthesitis and dactylitis. CRP levels decreased significantly from a median (IQR) at baseline of 2.90 (1.00; 8.95) mg/dL to 1.50 (0.43; 4.90) mg/dL (p=0.001) in the first month and the reduction was maintained until month 6. UPA also had a prednisone dose-sparing effect, with a reduction from a mean of 8.26 (5.58) mg/d to 7.73 ± 4.18 mg/d (p=0.049) in the first month. There were no changes in the mean dose of concomitant csDMARDs throughout the study
No serious Adverse Events (AEs) were reported. Mild adverse reactions, including viral infections, headache and gastrointestinal disorders, were reported in 23 (17.2%) patients.
UPA was discontinued in 44 (32.8%) patients due to lack of efficacy (n=28, 20.9%), adverse events (n=11, 8.2%) and patient decision (n=5, 3.7%). The AEs leading to UPA discontinuation were infection (n=4), anterior uveitis (n=2), thrombosis (n=1), surgery (n=1), pregnancy (n=1), urticaria (n=1) and diarrhea (n=1). The mean levels of hemoglobin, lymphocytes, neutrophils, platelets, lipids and transaminases remained stable throughout the follow-up period.
Our series showed a greater exposure to previous biological treatments and a higher proportion of women compared to the SELECT-PsA 2 trial. Despite these differences, UPA was effective in bDMARD-experienced patients with PsA in real-world settings, improving clinical manifestations, disease activity and nonspecific markers of active inflammation without the emergence of new safety signals.
In conclusion, our data suggest that UPA is effective with a rapid onset of action and is relatively safe for use in daily clinical practice for D2T PsA. Our study supports the findings of the SELECT-PsA 2 trial, confirming that UPA remains an effective and safe therapy for D2T PsA, despite some clinical differences between the study populations.
Real-word evidence studies like ours are essential for understanding how treatments perform in diverse, real-world settings, extending the insights from controlled clinical trials to broader patient groups. Our research reinforces that UPA is not only an effective therapeutic option but also well-tolerated, providing physicians with a reliable tool for managing D2T PsA.
This confirms UPA’s role as an important option in clinical practice, offering both rapid symptom relief and sustained efficacy for patients.
These finding suggest that upadacitinib is a rapid, effective and relatively safe therapeutic option for difficult-to-treat psoriatic arthritis under real-world conditions, supporting its use despite differing patient characteristics from clinical trial populations.
Citation: Galindez-Agirregoikoa E, Alonso RB (2025) Commentary on Upadacitinib in Difficult-to-Treat Psoriatic Arthritis: Real-World Data from 134 Patients''. Ann Clin Lab Vol.13 No.S6:001
Copyright: © 2025 Galindez-Agirregoikoa E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
