Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis: a systematic review meta-analysis

Tarp, Simon; Fürst, Daniel E.; Boers, Maarten; Luta, George; Bliddal, Henning; Tarp, Ulrik; Asmussen, Karsten; Brock, Birgitte; Døssing, Anna; Jørgensen, Tanja Schjødt; Thirstrup, Steffen; Christensen, Robin

doi:10.1093/rheumatology/kew442

Cited by 49 publications

(43 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, RA is also a risk factor for weakening of the bone structure in the axial and appendicular skeleton that will result in systemic bone loss . The treatment of RA has focused on the remission of the immune reaction in an attempt to halt bone erosion through the inhibition of immune inflammation; however, the efficacy is not satisfactory . The uncoupling of inflammation and bone erosion processes in a few individuals further complicates the treatment strategy, rendering anti‐inflammatory agents useless for restoring damaged bone .…”

Section: Discussionmentioning

confidence: 99%

“…(7) The treatment of RA has focused on the remission of the immune reaction in an attempt to halt bone erosion through the inhibition of immune inflammation; however, the efficacy is not satisfactory. (38) The uncoupling of inflammation and bone erosion processes in a few individuals further complicates the treatment strategy, rendering anti-inflammatory agents useless for restoring damaged bone. (39) Thus, drugs that can modulate both the inflammatory reactions and the bone structure of the disease might be suitable candidates for RA treatment.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction in Rheumatoid Arthritis

Zhu

Bai

et al. 2018

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Cannabinoid receptor 2 (CB2) has been implicated as an important clinical regulator of inflammation and malignant osteolysis. Here, we observed that CB2 expression was markedly higher in the collagen‐induced arthritis (CIA) mice synovium and bone tissues than in the noninflamed synovium and bone tissues. The CB2 selective agonist (JWH133) but not antagonist (SR144528) suppressed CIA in mice without toxic effects, as demonstrated by the decreased synovial hyperplasia, inflammatory responses, cartilage damage, and periarticular and systemic bone destruction. JWH133 treatment decreased the infiltration of pro‐inflammatory M1‐like macrophages and repolarized macrophages from the M1 to M2 phenotype. Similarly, activation of CB2 increased the expression of anti‐inflammatory cytokine interleukin (IL)‐10 and reduced the expression of pro‐inflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), IL‐1β, and IL‐6. In addition, JWH133 treatment attenuated osteoclast formation and osteoclastic bone resorption, and reduced the expression of receptor activators of the nuclear factor‐κB (NF‐κB) ligand (RANKL), matrix metallopeptidase‐9 (MMP‐9), tartrate‐resistant acid phosphatase (TRAP), cathepsin K (CTSK), and nuclear factor of activated T‐cells 1 (NFAT‐1) in CIA mice and osteoclast precursors, which were obviously blocked by pretreatment with SR144528. Mechanistically, JWH133 inhibited RANKL‐induced NF‐κB activation in the osteoclast precursors. We found that JWH133 ameliorates pathologic bone destruction in CIA mice via the inhibition of osteoclastogenesis and modulation of inflammatory responses, thereby highlighting its potential as a treatment for human rheumatoid arthritis. © 2018 American Society for Bone and Mineral Research.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction in Rheumatoid Arthritis

Zhu

Bai

et al. 2018

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…В настоящее время терапия РА состоит в коррекции аутоиммунных нарушений и воспалительных каскадов, преимущественно сигнального пути TNFa [10] и направлена на облегчение симптомов. Однако, возникающая со временем потеря эффективности терапевтического средства, возможно вследствие осложнений в других органах, ограничивает длительное назначение препаратов больным РА [11]. Поэтому возникает необходимость смены терапии, а вследствие этого необходима разработка новых терапевтических средств.…”

Section: Introductionunclassified

Upcoming value of gene expression analysis in rheumatology

Четина

Маркова

2018

BIOMED KHIM

View full text Add to dashboard Cite

Ревматические заболевания (РЗ) -это хронические воспалительные заболевания неизвестной этиологии, в ходе которых нарушаются функции сигнальных путей иммунной системы. Это сопровождается поражением ряда других тканей, болью и разрушением суставов. Современная терапия направлена на коррекцию патофизиологических и биохимических механизмов, ответственных за клиническую манифестацию заболевания. В связи с гетерогенностью больных РЗ существует необходимость персонифицированного лечения, выбор которого осложняется тем, что не все больные одинаково отвечают на терапию. Анализ экспрессии генов представляет инструмент для контроля заболевания и персонализации терапии больных с целью подавления воспаления и боли, а также замедления разрушения суставов.Ключевые слова: ревматические заболевания; ревматоидный артрит; экспрессия генов; провоспалительные цитокины; протеазы; боль

show abstract

“…Despite advances in the development of disease-modifying anti-rheumatic biologic drugs, approximately 40% of patients with rheumatoid arthritis (RA) fail to respond to treatment 1 . While the severity of RA fluctuates, biologic drugs are administered continuously at high concentrations, predisposing patients to significant adverse effects, such as increased risk of infection 2 . The development of therapeutics that can sense and respond to dynamically changing levels of endogenous inflammatory mediators may improve efficacy while mitigating the side effects of continuous biologic delivery [3][4][5] .…”

mentioning

confidence: 99%

A Genome-engineered Bioartificial Implant for Autoregulated Anti-Cytokine Drug Delivery

Choi

Collins

Springer

et al. 2019

Preprint

View full text Add to dashboard Cite

Biologic drug therapies are effective treatments for autoimmune diseases such as rheumatoid arthritis (RA) but may cause significant unwanted adverse effects, as they are administered continuously at high doses that can suppress the immune system. As the severity of RA fluctuates over time, targeted strategies that can dynamically sense and respond to changing levels of endogenous inflammatory mediators may achieve similar therapeutic efficacy while reducing risks of adverse effects. Using CRISPR-Cas9 genome editing, we engineered stem cells that harbor a synthetic gene circuit expressing biologic drugs to antagonize interleukin-1 (IL-1) or tumor necrosis factor a (TNF-a) in an autoregulated, feedback-controlled manner in response to activation of the endogenous chemokine (C-C) motif ligand 2 (Ccl2) promoter. To examine the in vivo therapeutic potential of this approach, cells were tissue-engineered to form a stable cartilaginous scaffold, which was implanted subcutaneously in mice with inflammatory arthritis. These bioengineered anti-cytokine implants mitigated arthritis severity as measured by joint pain, structural damage, and systemic and local inflammation. The coupling of synthetic biology with tissue engineering promises a wide range of potential applications for treating chronic diseases by generating custom-designed cells that regulate the expression of therapeutic transgenes in direct response to dynamically changing pathologic signals in the body.

show abstract

Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis: a systematic review meta-analysis

Abstract: PROSPERO CRD42014014842.

Cited by 49 publications

References 34 publications

Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction in Rheumatoid Arthritis

Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction in Rheumatoid Arthritis

Upcoming value of gene expression analysis in rheumatology

A Genome-engineered Bioartificial Implant for Autoregulated Anti-Cytokine Drug Delivery

Contact Info

Product

Resources

About