Background: Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who previously had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs).
Methods: In this 12-month, double-blind, active-controlled and placebo-controlled, phase 3 trial, we randomly assigned patients in a 2:2:2:1:1 ratio to receive one of the following regimens: tofacitinib at a 5-mg dose taken orally twice daily (107 patients), tofacitinib at a 10-mg dose taken orally twice daily (104), adalimumab at a 40-mg dose administered subcutaneously once every 2 weeks (106), placebo with a blinded switch to the 5-mg tofacitinib dose at 3 months (52), or placebo with a blinded switch to the 10-mg tofacitinib dose at 3 months (53). Placebo groups were pooled for analyses up to month 3. Primary end points were the proportion of patients who had an American College of Rheumatology 20 (ACR20) response (≥20% improvement from baseline in the number of tender and swollen joints and at least three of five other important domains) at month 3 and the change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score (scores range from 0 to 3, with higher scores indicating greater disability) at month 3.
Results: ACR20 response rates at month 3 were 50% in the 5-mg tofacitinib group and 61% in the 10-mg tofacitinib group, as compared with 33% in the placebo group (P=0.01 for the comparison of the 5-mg dose with placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the rate was 52% in the adalimumab group. The mean change in the HAQ-DI score was -0.35 in the 5-mg tofacitinib group and -0.40 in the 10-mg tofacitinib group, as compared with -0.18 in the placebo group (P=0.006 for the comparison of the 5-mg dose with placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the score change was -0.38 in the adalimumab group. The rate of adverse events through month 12 was 66% in the 5-mg tofacitinib group, 71% in the 10-mg tofacitinib group, 72% in the adalimumab group, 69% in the placebo group that switched to the 5-mg tofacitinib dose, and 64% in the placebo group that switched to the 10-mg tofacitinib dose. There were four cases of cancer, three serious infections, and four cases of herpes zoster in patients who received tofacitinib during the trial.
Conclusions: The efficacy of tofacitinib was superior to that of placebo at month 3 in patients with psoriatic arthritis who had previously had an inadequate response to conventional synthetic DMARDs. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Broaden ClinicalTrials.gov number, NCT01877668 .).
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http://dx.doi.org/10.1056/NEJMoa1615975 | DOI Listing |
Front Immunol
December 2024
Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, China.
Serine protease inhibitors (Serpins) are a protein superfamily of protease inhibitors that are thought to play a role in the regulation of inflammation, immunity, tumorigenesis, coagulation, blood pressure and cancer metastasis. Serpins is enriched in the skin and play a vital role in modulating the epidermal barrier and maintaining skin homeostasis. Psoriasis is a chronic inflammatory immune-mediated skin disease.
View Article and Find Full Text PDFFront Med (Lausanne)
December 2024
Department of Rheumatology and Medical Sciences, ASST Gaetano Pini-CTO Institute, Milan, Italy.
Objectives: The study aims to evaluate the applicability of the D2T psoriatic arthritis (PsA) definition, adapted from rheumatoid arthritis, within a single-center observational cohort of PsA patients treated with b/tsDMARDs. In addition, we aimed to establish a numerical index defining D2T-PsA based on the ratio of observed to expected failed b/tsDMARDs and to develop a predictive model identifying features associated with the D2T condition.
Methods: The study included 267 consecutive adult PsA patients receiving b/tsDMARDs, collecting demographic, clinical, and clinimetric data.
J Am Acad Dermatol
December 2024
Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. Electronic address:
Background: The risk of major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE) in patients with psoriatic disease receiving biologics is not fully understood.
Objective: This study aimed to investigate whether novel biologic therapies (IL-17, IL-12/23, and IL-23 inhibitors) for biologic-naïve patients with psoriasis or psoriatic arthritis (PsA) are associated with differences in the risks of MACE and VTE compared with those with TNF inhibitors.
Methods: An emulated target trial was designed by a nationwide cohort using data from the TriNetX Research Network.
Pediatr Rheumatol Online J
December 2024
Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Objective: This systematic search and review aimed to evaluate the available literature on discontinuation of adalimumab and other tumor necrosis factor inhibitors (TNFi) for patients with well-controlled chronic inflammatory arthritides.
Methods: We conducted a publication search on adalimumab discontinuation from 2000-2023 using PubMed, CINAHL, EMBASE, and Cochrane Library. Included studies evaluated adalimumab discontinuation approaches, tapering schemes, and outcomes including successful discontinuation and recapture after flare, in patients with well-controlled disease.
Semin Arthritis Rheum
December 2024
The IVF Unit, Hadassah Medical Center Mount Scopus, Jerusalem, Israel; Department of Obstetrics and Gynecology, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Objectives: To investigate female fertility in patients with rheumatoid arthritis (RA) exposed to biological drugs.
Methods: In this retrospective cohort study, based on an electronic health record database, 4517 women with RA were compared to 1415 patients with psoriatic arthritis (PsA). Patients were 18-40 years-of-age at diagnosis.
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