The introduction of biological treatments has improved the outlook for patients diagnosed with rheumatoid arthritis. There are now a range of different agents, targeting various pathways involved in ...the inflammatory process. Tocilizumab , a fully humanised anti-interleukin-6 receptor monoclonal antibody is licensed for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis.
This article reviews and appraises the available evidence regarding the efficacy and safety of tocilizumab in rheumatoid arthritis, as identified in PubMed and Embase searches.
Clinical trial data suggest that tocilizumab has similar efficacy both clinically and in reducing structural progression to that seen with the TNF inhibitors. Patients who might be particularly suitable for tocilizumab are those who have failed multiple TNF inhibitors, those with a high inflammatory response as part of their disease and those unable to tolerate methotrexate, given the good responses seen with monotherapy.
The development of biological drugs blocking tumour necrosis factor-alpha (TNF-α) has had a dramatic impact on the treatment of inflammatory arthritis in recent years. Golimumab is a fully human ...monoclonal antibody which inhibits TNF-α. It is licensed for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. In this review we evaluate the results of phase III studies using golimumab and explore the place of golimumab in the treatment of these diseases.
To review the available evidence for the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), synthetic and biological drug therapies for the different clinical manifestations of ...psoriatic arthritis (PsA) in order to provide data for the development of treatment recommendations by the European League Against Rheumatism (EULAR) taskforce.
A systematic literature review (SLR) of available treatments for PsA was performed using the largest electronic databases (MEDLINE, EMBASE and COCHRANE) by two working groups formed within the EULAR taskforce. This comprised a comprehensive sample of rheumatologists, dermatologists, epidemiologists and patients. The available evidence was reviewed for NSAIDs, synthetic disease modifying antirheumatic drugs (DMARDs), local and systemic corticosteroids and biologic drugs. All articles and abstracts published between 1962 and January 2010 were reviewed and considered and a meta-analysis of data on biological therapies was performed.
While little data are available on NSAIDs, glucocorticoids and synthetic DMARDs, the available evidence suggests an acceptable efficacy and safety profile of both NSAIDs and synthetic DMARDs (methotrexate, cyclosporine A, sulfasalazine and leflunomide) in PsA. More evidence is available (level 1B) supporting the efficacy of anti-tumour necrosis factor (anti-TNF) agents (adalimumab, etanercept, golimumab and infliximab) in treating the signs and symptoms of PsA as well as reducing radiographic progression. Registry data show no new safety concerns, although the numbers studied to date are relatively small.
This SLR reveals some evidence to support the use of NSAIDs and synthetic DMARDs and good evidence for the efficacy of anti-TNF therapy in PsA.
Rheumatologists have largely conceptualised joint disease in inflammatory and degenerative arthritis in terms of bone, cartilage and the synovial lining, but have tended to overlook other integral ...components of the joints which are attached close to joint margins. We discuss these structures under the umbrella term of ‘appendages’. These structures include ligaments, tendons, entheses or joint insertions, regional fibrocartilages, bursae and other peri-articular joint structures including fat pads and nails. In this review, we highlight how these structures play key pathophysiological roles in inflammatory arthritis and we emphasise how an understanding of these structures is collectively important for both clinical practice and future rheumatological research.
Evaluation of the preclinical phases of the classic autoimmune diseases including rheumatoid arthritis has been facilitated by the availability of autoantibody and genetic markers that point firmly ...towards the early dysregulation of the adaptive immune responses. The association of psoriatic disease with the human leucocyte antigen-Cw0602 (HLA-Cw0602) gene has likewise led to the perception that autoimmunity has a pivotal role in early psoriatic arthritis (PsA). However, this HLA-Cw0602 genetic association does not appear to hold for PsA or associated nail, scalp and intergluteal skin involvement. Of note, these three sites of psoriasis are predictive of PsA evolution. For initiation of both skin and nail disease there is a link with Koebnerisation, or site-specific trauma. Nail disease is most common in the dominant hand thumbnail, pointing towards local tissue factors as disease initiators Likewise, for PsA, there is also good evidence for a history of previous joint trauma and histological studies showing microdamage in normal entheses which are typical locations where PsA frequently occurs. Furthermore, subclinical enthesopathy including osteitis is common in subjects with psoriasis but without arthritis. Collectively, these findings indicate that the classic model of adaptive immune dysregulation does not generally hold for the early stages of PsA. The way in which knowledge pertaining to tissue-specific factors in PsA, combined with the emerging data relating to monogenic disorders and animal models, points towards perturbation in the healing response and dysregulation of innate immune responses in early PsA is discussed. The way in which this model explains the clinical disconnect between skin and joint disease and the emerging human data that support it are demonstrated.
The 2011 annual meeting in Naples, Italy, of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) began with a Trainees Symposium, which has become an important aspect ...of the meeting. In 2011, 25 trainees currently involved in research in psoriasis or psoriatic arthritis were invited to deliver an oral abstract or poster presentation. We present a brief overview of the oral and poster presentations, which show the diversity and focus of current research performed by members and trainees of GRAPPA.
Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5+-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 is an ...RNA sensor and a key pattern recognition receptor for the SARS-CoV-2 virus.
This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018 and December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5+-DM outbreak.
Sixty new anti-MDA5+, but not other MSAs surged between 2020 and 2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strong IFIH1 (gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, and IFIH1 strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. The IFIH1 rs1990760TT variant blunted such response.
A distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms.
This work was supported in part by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC), and in part by the National Institutes of Health (NIH) grant R01-AI155696 and pilot awards from the UC Office of the President (UCOP)-RGPO (R00RG2628, R00RG2642 and R01RG3780) to P.G. S.S was supported in part by R01-AI141630 (to P.G) and in part through funds from the American Association of Immunologists (AAI) Intersect Fellowship Program for Computational Scientists and Immunologists.
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