Infliximab and etanercept have distinct actions but similar effects on cytokine profiles in rheumatoid arthritis

Takeshita, Masaru; Suzuki, Katsuya; Kikuchi, Jun; Izumi, Kiyotaka; Kurasawa, Takahiko; Yoshimoto, Keiko; Amano, Koichi; Takeuchi, Tsutomu

doi:10.1016/j.cyto.2015.04.011

Cited by 14 publications

(8 citation statements)

References 37 publications

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“…TNF-b is a proinflammatory cytokine, considered to have almost the same effect as TNF-a. 34,35 Second, according to our results, patients >30-y old were independent predictor for incomplete response to the combined treatment. More than 50% of our patients were younger than 30-y old, whereas patients in above-mentioned three studies were older.…”

Section: Discussionsupporting

confidence: 50%

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

Tan

Xiao

et al. 2017

OncoImmunology

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Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD involves corticosteroids. However, fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory aGVHD (SR-aGVHD) remains around 70%. To date, no consensus has been reached regarding the optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi-center clinical trial to assess the efficacy and safety of a novel approach to treat severe (grades III-IV) SR-aGVHD with the combination of basiliximab and etanercept. Sixty-five patients with severe SR-aGVHD from six centers were included. The median number of basiliximab infusions was 4 (range 2-11) and of etanercept was 9 (range 2-12). At day 28 after starting the combination treatment, overall response (complete and partial response: CRCPR) to second-line treatment was 90.8% with 75.4% being CR. The incidences of CR per organ were 100%, 73.8%, and 79.7% for skin, liver, and gut involvement, respectively. Patients >30-y old (p D 0.043, RR D 3.169), development of grades III-IV liver aGVHD (p D 0.007, RR D 5.034) and cytomegalovirus (CMV) reactivation (p D 0.035, RR D 4.02) were independent predictors for incomplete response. Combined treatment with basiliximab and etanercept resulted in improved CR to visceral aGVHD and significantly superior 2-y overall survival (54.7% vs. 14.8%, p <0.001) compared with classical salvage treatments. Our data suggest that the combination of basiliximab and etanercept may constitute a promising new treatment option for SR-aGVHD.

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Section: Discussionsupporting

confidence: 50%

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

Tan

Xiao

et al. 2017

OncoImmunology

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“…Interestingly, while etanercept showed good clinical response in our patient, as indicated by decline of BASDAI score and inflammatory indicators such as ESR and CRP, cytokine levels such as IL-2 and TNF-alpha increased first for 8 weeks before they further decreased within normal ranges (Murdaca et al, 2018). The phenomenon, suggesting that elevated cytokine levels did not always correspond with increased disease activity, was also observed in other clinical studies involving patients treated with etanercept under conditions of rheumatic autoimmune diseases (Schulz et al, 2014;Takeshita et al, 2015;Walters et al, 2016). For example, Walters et al (2016) reported that TNF-alpha and IL-17 increased significantly for about 4 and 8 weeks respectively in etanercept but not adalimumab-treated subjects, while the clinical improvement of both treatments was similar.…”

Section: Discussionsupporting

confidence: 72%

Probable Drug Interaction Between Etanercept and Cyclosporine Resulting in Clinically Unexpected Low Trough Concentrations: First Case Report

Wen

Chen

et al. 2020

Front. Pharmacol.

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Preclinical studies have shown that anti-cytokine therapies could alter drug dispositions through affecting cytochrome P450 synthesis; however, evidence and case reports evaluating clinical relevance of this interaction are scarce. This is the first reported case of interaction between cyclosporine (CsA) and etanercept in a 42-year-old male patient with ankylosing spondylitis and immunoglobulin A nephropathy in whom cytokine levels were monitored both before and after CsA initiation. The initiation of etanercept led to at least 2.5-folds increase in total clearance of CsA. After comprehensive assessment and stepwise exclusion of alternative causes, it was considered that inflammation resolution with etanercept administration has highly induced clearance of CsA, probably mediated by interleukin-2. The case has shown that co-administration of CsA and anti-cytokine therapies such as etanercept needs close monitoring of trough levels. Physicians and pharmacists should be aware of similar interactions especially when the biological therapy is initiated or discontinued and for patients undergoing acute inflammation phase. Monitoring cytokine levels should be considered when drug-cytokine interaction is suspected.

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“…Since IFX as an anti-TNFα antibody only binds to TNFα, not to its receptor [ 38 ], the mechanism through which IFX elevated serum TNFα level was difficult to explain, despite improvements of active symptoms and serum ESR and CRP levels. This may be in line with the context of the study of Takeshita et al [ 39 ] which suggests that evaluation of TNFα level after IFX therapy is difficult due to interference from drug–cytokine complexes [ 37 ]. However, patients with remission had significantly lower serum levels of TNFα at baseline compared to those with non-remission.…”

Section: Discussionsupporting

confidence: 72%

Infliximab biosimilar CT-P13 therapy in patients with Takayasu arteritis with low dose of glucocorticoids: a prospective single-arm study

Park

Lee

et al. 2018

Rheumatol Int

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To evaluate the efficacy and safety of infliximab biosimilar CT-P13 in patients with active Takayasu arteritis (TAK). In this single-center open-label trial, patients with active TAK received CT-P13 at a starting dose of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks up to week 46. They were followed up until week 54. From week 14 to week 46, patients with inadequate response received increased dose of CT-P13 by 1.5 mg/kg. Concomitant prednisolone was allowed ≤ 10 mg/day. The primary efficacy end point was the achievement of partial or complete remission at week 30. All patients underwent positron emission tomography–computed tomography (PET–CT) at baseline and week 30. Twelve patients with TAK received CT-P13; one patient with protocol violation was excluded from analysis. Nine (81.8%) patients had taken concomitant prednisolone with median dose of 5.0 mg/day. At week 30, three (27.3%) patients achieved complete remission and six (54.5%) patients achieved partial remission. Statistically significant improvements in modified Indian Takayasu Clinical Activity Score (ITAS2010), ITAS-A, and serum levels of erythrocyte sedimentation rate and C-reactive protein were seen at week 30 from baseline. PET parameters were significantly reduced from baseline to week 30, including maximum standardized uptake value, target-to-vein ratio, target-to-liver ratio, and PET Vascular Activity Score. There were no serious adverse events. Treatment with CT-P13 may lead to improvement in clinical, radiographic, and serological activities with lower glucocorticoid requirement in TAK.Trial registration number NCT02457585.Electronic supplementary materialThe online version of this article (10.1007/s00296-018-4159-1) contains supplementary material, which is available to authorized users.

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Infliximab and etanercept have distinct actions but similar effects on cytokine profiles in rheumatoid arthritis

Cited by 14 publications

References 37 publications

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

Probable Drug Interaction Between Etanercept and Cyclosporine Resulting in Clinically Unexpected Low Trough Concentrations: First Case Report

Infliximab biosimilar CT-P13 therapy in patients with Takayasu arteritis with low dose of glucocorticoids: a prospective single-arm study

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