OBJECTIVE: To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt.
METHODS: CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score - C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP <2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups.
RESULTS: Following CS treatment, 142 patients were early responders; 55 early insufficient responders received Standard-CS and 55 Bio-induction-CS. Superiority of Bio-induction-CS over Standard-CS could not be demonstrated (ß=-0.204, (95% CI -0.486 to 0.078), p=0.157) for the primary outcome. More patients on Bio-induction-CS achieved DAS28-CRP <2.6 at 28 weeks after randomisation (59% (95% CI 44% to 72%) vs 44% (95% CI 31% to 59%) in Standard-CS) and they were treated less frequently with b/tsDMARDs at W104 (19/55, 35%) compared with Standard-CS (29/55, 53%).
CONCLUSIONS: Half of the patients responded well to initial COBRA-Slim induction therapy. In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104.
BACKGROUND: NCT03649061.
UNASSIGNED: S59474, EudraCT number: 2017-004054-41.

The effects of calcitonin gene-related peptide (CGRP) on atherosclerosis remain unclear. We used apolipoprotein E-deficient (ApoE-/-) mice to generate double-knockout ApoE-/-:CGRP-/- mice lacking alpha CGRP. ApoE-/-:CGRP-/- mice exhibited larger atherosclerotic plaque areas, peritoneal macrophages with enhanced migration functions, and elevated levels of the inflammatory cytokine tumor necrosis factor (TNF)-⍺. Thus, we also explored whether inhibiting TNF-⍺ could improve atherosclerosis in ApoE-/-:CGRP-/- mice by administering etanercept intraperitoneally once a week (5 mg/kg) alongside a high-fat diet for 2 weeks. This treatment led to significant reductions in aortic root lesion size, atherosclerotic plaque area and macrophage migration in ApoE-/-:CGRP-/- mice compared with mice treated with human IgG (5 mg/kg). We further examined whether results observed in ApoE-/-:CGRP-/- mice could similarly be obtained by administering a humanized monoclonal CGRP antibody, galcanezumab, to ApoE-/- mice. ApoE-/- mice were subcutaneously administered galcanezumab at an initial dose of 50 mg/kg, followed by a dose of 30 mg/kg in the second week. Galcanezumab administration did not affect systolic blood pressure, serum lipid levels, or macrophage migration but led to a significant increase in lipid deposition at the aortic root. These findings suggest that alpha CGRP plays a critical role in inhibiting the progression of atherosclerosis.

UNASSIGNED: Biological therapies are effective for psoriasis, but patient responses vary, often requiring therapy switching or discontinuation.
UNASSIGNED: To identify physicians\' prescribing patterns of biological therapies at a referral tertiary center in Saudi Arabia and assess the probability of biologic persistence following treatment initiation.
UNASSIGNED: We conducted a retrospective study of biologic-naïve adult psoriasis patients who initiated therapy from October 2013 to July 2022 in Dammam. Descriptive statistics and a Kaplan-Meier analysis evaluated treatment persistence at 6, 12, 24, and 36 months.
UNASSIGNED: A total of 151 patients received adalimumab (n = 89), etanercept (n = 17), risankizumab (n = 30), ustekinumab (n = 14), and ixekizumab (n = 1). At 6 months, all therapies demonstrated 100% persistence. At 12 months, persistence was highest for ustekinumab (100%) and lowest for etanercept (88.2%). At 24 months, ustekinumab maintained 100% persistence, followed by risankizumab (96.6%), adalimumab (94.3%), and etanercept (76.4%). At 36 months, risankizumab had the highest persistence (96.6%), followed by adalimumab (83.1%), ustekinumab (78%), and etanercept (70.6%). The most common reasons for discontinuation were lack of effectiveness and intolerability.
UNASSIGNED: This study shows changing psoriasis treatment patterns with new therapies. Risankizumab demonstrated high long-term persistence, while etanercept and ustekinumab showed declining persistence, suggesting evolving treatment considerations.

UNASSIGNED: The aim of this study was to assess the efficacy and safety of etanercept (ETA) use in juvenile idiopathic arthritis (JIA).
UNASSIGNED: The 24-month data of patients with JIA on etanercept in a single center were evaluated retrospectively. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), and JIA-American College of Rheumatology (ACR) improvement criteria. Safety assessments were based on adverse event (AE) reports.
UNASSIGNED: The study included 152 patients with JIA. The mean age at diagnosis of JIA was 8.5 ± 4.4 years, and treatment with ETA started at a mean age of 11.1 ± 4.4 years. The mean duration of ETA use was 16 ± 11.1 months. The mean JADAS10 score at baseline was 18.5 ± 5.9. By the third month, it had reduced to 8.6 ± 6.6 and by the sixth month to 5.7 ± 6. By the twelfth month, the JADAS10 score was 4.9 ± 6.7, and by the twenty-fourth month, it had worsened to 7.3 ± 7.8. ACR50 response was achieved in 79.6% of patients at 3 months, 67.1% at 6 months, 79.3% at twelfth months, 70.7% at the twenty-fourth month. During ETA treatment, 10 patients required hospitalization for serious infections.
UNASSIGNED: Etanercept is a safe and effective option for patients with JIA. However, variations in response between JIA subtypes highlight the need for individualized treatment strategies.

Seven of the 11 newer medications recently or soon to be approved to treat rheumatologic diseases discussed in this article are biologic agents and reflect the current ability of science to target specific components of the immune system. The other agents are molecules that are directed against specific immune pathway targets as well. All have shown superiority to placebo and in some cases have been compared to currently accepted therapies. Safety issues are generally centered around infections due to the immune-interrupting nature of these therapies.

Treatment for pregnant women with psoriasis is limited by the lack of information typically related to clinical trials. While anti-tumor necrosis factor (TNF) drugs offer therapeutic benefits, their safety during pregnancy is a concern. Notably, certolizumab is comparatively safer than adalimumab, etanercept, infliximab, and golimumab according to the current recommendations. Thus, this study aimed to conduct a pharmacovigilance comparative analysis of maternal and neonatal outcomes associated with certolizumab versus other anti-TNF drugs by using data from EudraVigilance. A descriptive analysis was performed of Individual Case Safety Reports (ICSRs) associated with an anti-TNF drug and related to the pregnant patients with psoriasis from 2009 and 2023, focusing our analysis on the specific pregnancy outcomes and fetal/neonatal disorders. The most common pregnancy-related adverse event was spontaneous abortion, predominantly related to adalimumab and certolizumab. Certolizumab was also reported in cases of caesarean section, gestational diabetes, abortion, fetal death, fetal distress syndrome, pre-eclampsia, and premature separation of placenta. Generally, the findings from our study depicted a safety profile that overlapped for each anti-TNF drug, both in maternal/neonatal outcomes and other adverse events, suggesting no substantial differences between treatments. We advocate for further investigations before making concrete recommendations.

BACKGROUND: The objective of this phase III clinical randomized trial was to establish the therapeutic equivalence of biosimilar etanercept (bio-etanercept) with original etanercept (O-etanercept) for patients diagnosed with rheumatoid arthritis.
METHODS: The study (NCT04079374) enrolled patients with moderate to high disease activity rheumatoid arthritis. Enrolled patients were randomized 1:1 into 2 treatment groups, 1 receiving bio-etanercept (study drug) and the other receiving O-etanercept (comparator) at a dose of 25mg twice weekly, for 24 weeks. The primary efficacy endpoint was the number of patients with an ACR20 response after 24 weeks of treatment. Safety (adverse reaction/adverse event) and immunogenicity of both drugs were evaluated.
RESULTS: Among 156 patients (79 in the bio-etanercept group and 77 in the O-etanercept group) who completed 24-week treatment and 4-week follow-up, 82.3% (65 patients) and 90.9% (70 patients) achieved an ACR20 response in the bio-etanercept and O-etanercept groups, respectively. There was no significant difference between the 2 groups (P = .16). No significant differences in the occurrence of adverse reactions/adverse events were found between the 2 groups regardless of severity (P = .63 for mild, P = .43 for moderate and P > .99 for severe). The development of antibodies in the bio-etanercept group was observed in 4 (5.1%; visit 6), 4 (5.0%; visit 9), and 3 (3.8%; visit 11) patients, and in 5 (6.4%), 5 (6.5%), and 3 (4.1%) patients in the O-etanercept group. The differences between the 2 groups were not significant (P > .99).
CONCLUSIONS: This study showed that bio-etanercept was equivalent to the reference formulation.

OBJECTIVE: Mounting evidence suggests that histone deacetylases (HDAC) inhibitors reduce cartilage destruction in animal models of osteoarthritis (OA). Tumor necrosis factor (TNF)-α-blocking treatment for OA may provide effective joint protection by slowing joint damage. To investigate the effects of intraperitoneal administration of etanercept (a TNF-α inhibitor) on OA development in rats and changes in the nociceptive behavior of rats and expression of HDACs, RUNX2, and MMP13 in cartilage.
METHODS: Induction of OA in Wistar rats was accomplished through anterior cruciate ligament transection (ACLT). One or five milligrams (mg) of etanercept was administered intraperitoneally for 5 consecutive weeks after ACLT to the ACLT + etanercept (1 and 5 mg/kg) groups. Nociceptive behavior and changes in knee joint width were analyzed. Cartilage was evaluated histologically and immunohistochemically.
RESULTS: ACLT + etanercept significantly improved mechanical allodynia and weight-bearing distribution compared to ACLT alone. In OA rats treated with etanercept, cartilage degeneration and synovitis were significantly less pronounced than those in ACLT rats. OA-affected cartilage also showed reduced expression of HDAC 6, 7, RUNX-2, and MMP-13 in response to etanercept but increased expression of HDAC4.
CONCLUSIONS: Our study demonstrated that etanercept therapy (1) attenuated the development of OA and synovitis in rats, (2) reduced nociception, and (3) regulated chondrocyte metabolism, possibly by inhibiting cell HDAC6 and HDAC7, RUNX2, and MMP13 and increasing HDAC4 expression. Based on new evidence, etanercept may have therapeutic potential in OA.

OBJECTIVE: Primary chronic Non-Bacterial Osteomyelitis of the jaw is a rare auto-inflammatory disease of unknown aetiology that bears pathophysiological resemblance to both the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome in adults and chronic recurrent multifocal osteomyelitis (CRMO) in children. Both SAPHO and CRMO respond to TNF-alpha blockade. Previously reported treatment regimens in CNOM including non-steroidal anti-inflammatory drugs, corticosteroids, antibiotics, anti-resorptive therapy, and surgery all bear disappointing results. TNF- α blockade is suggested as a treatment option by some experts but this is not backed by any clinical data.We sought to retrospectively and exhaustively report our experience of anti-TNF alpha therapy in refractory CNOM.
METHODS: Fifteen patients with refractory CNOM and high disease burden were referred to our centre. TNF- α blockade was attempted in 10 cases, given its efficacy in neighbouring diseases, its good tolerance profile and failure of previous treatment strategiesWe herein retrospectively report detailed outcomes for all patients having received anti-TNF alpha therapy for this indication in our centre.
RESULTS: TNF-α-targeting therapy resulted in a rapid and sustained remission in a majority of patients with CNOM, without serious adverse events. Treatment was tapered and stopped without relapse in some patients despite a refractory course of several years. Male sex seems to be associated with a poorer outcome.
CONCLUSIONS: Our results suggest that blocking TNF-α is efficient and safe in CNOM.

BACKGROUND: We present an unusual case of a 28-year-old rheumatologic male patient who developed eosinophilia while he was on etanercept therapy first and then on golimumab.
METHODS: Although eosinophilia is rarely reported in the literature as a side-effect of various Tumor Necrosis Factor-alpha [TNF-alpha] antagonists, it represents a riddle about the future treatments of these patients since the persistence of therapy might lead to the onset of dermatologic or visceral eosinophilic complications in such patients.
CONCLUSIONS: Furthermore, the pathogenesis of eosinophilia is still unknown, and all the proposed hypotheses do not explain the eosinophilic proliferation in certain subjects.