PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 11759232

[New therapy developments in rheumatoid arthritis].

H M Lorenz·J R Kalden
View original source ↗Export metadata ↓

Abstract

Despite the anti-TNF alpha based progress in the treatment of RA, it is necessary to further optimize study designs and reports (Etanercept/MTX combination with results of radiological progression; publication of D2E7 trials; combination of D2E7 with MTX). Moreover, innovative immunobiologicals (PEG-TNFRI, PEG-TNF alpha antibody fragments, soluble TNFRI, CTLA4-Ig, CD40 ligand antibody, antibodies against IFN-gamma, IL-6, IL-12, IL-15, IL-18, complements), inhibitors of TNF alpha translation (peptides, anti-sense constructs) or TNF alpha synthesis (targeting NF kappa B, p38 MAP-kinase, phosphodiesterase IV, TNF alpha converting enzyme) are forthcoming. Principally different are inhibitors of complement convertases or collagenase as well as vaccination studies or trials trying to induce T cell anergy. Furthermore, for patients with MTX side effects, alternative DMARDs need to be tested along with TNF alpha blockers. Combination studies of TNF alpha constructs with other immunobiologicals (anti-CD4, IL-4, IL-10, IL-1RA) should be evaluated. To date, TNF alpha blockers have been evaluated in very early RA. Finally, a step-down trial will test whether--after induction of remission with a TNF alpha blocker plus MTX--replacement of the TNF alpha blocker with MTX alone or in combination with leflunomide will be able to keep disease activity suppressed for a longer duration.

Explore related subjects

Antirheumatic AgentsArthritis, RheumatoidBiological ProductsClinical Trials as TopicDrug Therapy, CombinationHumansMethotrexateTumor Necrosis Factor-alphaEnglish AbstractJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

H M Lorenz, J R Kalden. 2001. [New therapy developments in rheumatoid arthritis].. https://doi.org/10.1007/s003930170032

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Interleukin-1beta induced activation of nuclear factor-kappab can be inhibited by novel pharmacological agents in osteoarthritis.

OBJECTIVES: To investigate the importance of activation of the transcription factor, nuclear factor-kappaB (NF-kappaB) by interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) in the pathogenesis of osteoarthritis (OA) and assess its suitability as a target for therapy by determining its role in the induction of the cytokine IL-6 and the degenerative enzymes, matrix metalloproteinase (MMP)-1 and MMP-3 in vitro. METHODS: Three distinct cellular models, derived from primary OA tissue, were employed, namely, fibroblast-like synoviocytes (OA-SF); co-cultures containing phenotypic macrophage-like and fibroblast-like cells (OA-COCUL); and primary OA synovial tissue explants (OA-EXP). These were treated with specific inhibitors of IL-1beta, TNF-alpha and NF-kappaB to assess their differential role in the production of pathologically relevant mediators, specifically IL-6, MMP-1, MMP-3 and the tissue inhibitor of metalloproteinases-1 (TIMP-1), which were quantified by enzyme-linked immunosorbent assay. RESULTS: Inhibition of NF-kappaB by a novel agent, RO100 at a dose of 0.1 microM, exerted significant (P < 0.05) repression of IL-6, MMP-1 and MMP-3 production in OA-SF. Notably, neither TIMP-1 production nor cell viability was significantly affected at the dose tested. These data were reproduced in OA-EXP, which might be considered as having greater physiological relevance. Interestingly, comparable efficacy was noted using IL-1beta and TNF-alpha neutralizing antibodies in OA-COCUL. CONCLUSIONS: We have demonstrated that a novel pharmacological inhibitor of NF-kappaB, RO100 inhibits pathological mediators of OA progression with equivalent efficacy as established IL-1beta and TNF-alpha neutralizing strategies. Our findings highlight a potential for developing NF-kappaB targeted therapeutics for positively regulating disease activity and improving clinical outcome in OA.

Antirheumatic Agents↗
PubMed2007

Patients with rheumatoid arthritis undergoing surgery: how should we deal with antirheumatic treatment?

OBJECTIVES: To review published data on the perioperative management of antirheumatic treatment and perioperative outcome in patients with rheumatoid arthritis (RA). METHODS: The review is based on a MEDLINE (PubMed) search of the English-language literature from 1965 to 2005, using the index keywords "rheumatoid arthritis" and "surgery". As co-indexing terms the different disease-modifying antirheumatic drugs (DMARDs) as well as nonsteroidal anti-inflammatory drugs (NSAIDs) and "glucocorticoids" were used. In addition, citations from retrieved articles were scanned for additional references. Furthermore, because the number of published articles is so limited, relevant abstracts presented at congresses were included in the analysis. RESULTS: Continuation of methotrexate (MTX) appears to be safe in the perioperative period. Only a limited number of studies address the use of leflunomide and the results are conflicting. Because of the very long drug half-life, its discontinuation would need to be of long duration and is probably not necessary. Data on hydroxychloroquine do not show increased risks of infection. Regarding sulfasalazine, there are no studies from which definite answers could be drawn on whether it should be withheld perioperatively. Preliminary data show that the risk of infections during treatment with TNF-blocking agents may be lower than initially expected. The only available recommendation (Club Rhumatismes et Inflammation, CRI) suggests discontinuing the drugs before surgery for several weeks, depending on the risk of infection and the drug used. They should not be restarted until wound healing is complete. To avoid the antiplatelet effect during surgery, NSAIDs other than aspirin should be withheld for a duration of 4 to 5 times the drug half-life. Patients with chronic glucocorticoid therapy and suppressed hypothalamic-pituitary-adrenal (HPA) axis need perioperative supplementation. CONCLUSIONS: While continuation of MTX likely is safe, data on other DMARDs are sparse. In particular, more data on the perioperative use of the biologic agents are needed.

Antirheumatic Agents↗
PubMed2007

[Revision of the recommendations of the Commission on Pharmacotherapy of the German society for Rheumatology. Therapy with tumour necrosis factor blockers for inflammatory rheumatic illnesses].

Inflammatory rheumatic illnesses are associated with various types of pain as well as handicaps. The so called basic therapies are not sufficiently effective in many patients or are terminated due to side effects. This is where tumor necrosis factor blockers (TNF) can be used. In many cases, they lead to a substantial improvement of the symptoms, a reduction in disease related laboratory parameters, improvement in quality of life to stopping disease related damage when their effect is rapid. Common and severe side effects are few, although long-term data are still limited. The following contribution lists recommendations for the indications and symptomatology for the use of TNF blockers.

Antirheumatic Agents↗