Concept: TNF inhibitor
In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at 3 months). Tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, biosimilars), abatacept, tocilizumab and, under certain circumstances, rituximab are essentially considered to have similar efficacy and safety. If the first bDMARD strategy fails, any other bDMARD may be used. The recommendations also address tofacitinib as a targeted sDMARD (tsDMARD), which is recommended, where licensed, after use of at least one bDMARD. Biosimilars are also addressed. These recommendations are intended to inform rheumatologists, patients, national rheumatology societies and other stakeholders about EULAR’s most recent consensus on the management of RA with sDMARDs, glucocorticoids and bDMARDs. They are based on evidence and expert opinion and intended to improve outcome in patients with RA.
Phase 2 psoriasis studies with the Fc-free, PEGylated, anti-tumor necrosis factor biologic certolizumab pegol demonstrated meaningful clinical activity.
This 28-week, phase IIIb study assessed safety and maintenance of response to certolizumab pegol (CZP) in a diverse population of rheumatoid arthritis (RA) patients, stratified by prior anti-TNF exposure, concomitant methotrexate (MTX) use and disease duration. The ability to predict achievement of low disease activity (LDA) at week 28 from improvements in Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), swollen joint count (SJC) and Clinical Disease Activity Index (CDAI) up to week 12 was assessed.
Six biologic agents are currently approved for the treatment of IBD: four anti-TNF agents (infliximab, adalimumab, golimumab and certolizumab pegol) and two anti-integrin agents (natalizumab and vedolizumab). In Crohn’s disease and ulcerative colitis refractory to standard medications, treatment choice among available biologic agents can be challenging. Several parameters should be taken into account to help physicians through the decision-making process, including the comparative effectiveness and long-term safety profile, availability and labelling in the prescriber’s country, international guidelines, and cost, as well as patient preferences (such as the route of administration). Herein, we provide practical insights on the use of biologic agents in IBD. The results of head-to-head trials between biologic agents are eagerly awaited to guide decision-making regarding the choice of first-line biologic agents and to determine whether switching within the same drug class or swapping (switching out of the drug class) is preferable after primary or secondary loss of response to the first biologic agent. In the near future, treatment algorithms might evolve with the launch of new drugs (such as ustekinumab, tofacitinib and etrolizumab) and the increased use of biosimilars.
The risk of malignancies on TNF-α antagonists is controversial. The aim of this survey was to assess cancer risk on TNF-α antagonists in adult rheumatoid arthritis patients, including the five marketed drugs (infliximab, etanercept, adalimumab, golimumab and certolizumab) used in line with the New Drug Application. Furthermore, the relative interest of modified intention to treat or per protocol analyses to assess such sparse events remains unknown.
Tumor necrosis factor-α (TNF-α) blockers are a popular therapeutic choice in a number of inflammatory diseases. Thus far, five TNF- α blockers have been approved for clinical use (etanercept, infliximab, adalimumab, golimumab. and certolizumab). Despite being considered relatively safe, serious side effects associated with immune suppression have been reported, including central and peripheral nervous system (CNS) demyelinating disorders. It is still elusive whether these events are mere coincidence or a side effect of anti-TNF-α use. In this paper, we review the published case reports of CNS demyelination associated with anti-TNF-α therapy and present the follow-up of our 4 previously reported patients who developed neurologic symptoms suggestive of CNS demyelination after having received anti-TNF-α treatment. We also discuss the possible role of TNF-α blockers in demyelination.
Objective Early identification of patients unlikely to achieve good long-term disease control with anti-TNF therapy in axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) is important for physicians following treat-to-target recommendations. Here we assess associations between disease activity or clinical response during the first 12 weeks (wks) of treatment and attainment of treatment targets at Wk48 in axSpA and PsA patients receiving certolizumab pegol (CZP). Methods The relationship between disease activity or clinical response during the first 12 wks of treatment, and achievement of Wk48 targets (axSpA: ASDAS-CRP inactive disease or BASDAI <2 with normal CRP; PsA: minDA), was assessed post-hoc using RAPID-axSpA (NCT01087762) and RAPID-PsA (NCT01087788) trial data. Results A clear relationship between disease activity from Wk2 to Wk12 and achievement of Wk48 treatment targets was observed in both axSpA and PsA populations. In axSpA, Wk48 ASDAS inactive disease was achieved by 0% (0/21) of patients with ASDAS very high disease activity at Wk12, compared to 68% (34/50) of patients with Wk12 ASDAS inactive disease. For PsA, Wk48 minDA was achieved by 0% (0/26) of patients with DAS28(CRP) >5.1 at Wk12, compared to 73% (57/78) of patients with DAS28(CRP) <2.6. Similar results were observed regardless of disease activity measure used. Clinical response at Wk12 also predicted Wk48 outcomes, though to a lesser extent than disease activity. Conclusion Using disease activity and clinical response state during the first 12 wks of CZP treatment, it was possible to identify a subset of axSpA and PsA patients unlikely to achieve long-term treatment goals. This article is protected by copyright. All rights reserved.
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 2 years ago
Overexpression of TNF contributes to pathogenesis of multiple autoimmune diseases, accounting for a remarkable success of anti-TNF therapy. TNF is produced by a variety of cell types, and it can play either a beneficial or a deleterious role. In particular, in autoimmunity pathogenic TNF may be derived from restricted cellular sources. In this study we evaluated the feasibility of cell-type-restricted TNF inhibition in vivo. To this end, we engineered MYSTI (Myeloid-Specific TNF Inhibitor)-a recombinant bispecific antibody that binds to the F4/80 surface molecule on myeloid cells and to human TNF (hTNF). In macrophage cultures derived from TNF humanized mice MYSTI could capture the secreted hTNF, limiting its bioavailability. Additionally, as evaluated in TNF humanized mice, MYSTI was superior to an otherwise analogous systemic TNF inhibitor in protecting mice from lethal LPS/D-Galactosamine-induced hepatotoxicity. Our results suggest a novel and more specific approach to inhibiting TNF in pathologies primarily driven by macrophage-derived TNF.
Anti-tumor necrosis factor agents (anti-TNFs) are frequently used in combination with methotrexate to treat rheumatoid arthritis (RA). We investigated the effect of background methotrexate dose, in combination with anti-TNF certolizumab pegol (CZP), on treatment efficacy and safety in RA patients.
To compare drug survival on adalimumab, etanercept and infliximab in patients with rheumatoid arthritis (RA).