Rheumatoid Arthritis: Rubbert-Roth A

Rubbert-Roth A, Finckh A. · Department of Internal Medicine, University of Cologne, Josef-Stelzmann-Strasse, 50924 Cologne, Germany. · Arthritis Res Ther. · Pubmed #19368701 links to  free full text

Abstract: Conventional disease-modifying antirheumatic drugs such as methotrexate are the mainstay of treatment for rheumatoid arthritis. More recently, biologic agents such as etanercept, infliximab and adalimumab, which act by inhibiting tumour necrosis factor (TNF), have become available. TNF inhibitors have proved to be very effective in patients not responding to conventional disease-modifying antirheumatic drugs. However, about 20% to 40% of patients treated with a TNF inhibitor fail to achieve a 20% improvement in American College of Rheumatology criteria, and more lose response over time (secondary failure or acquired therapeutic resistance) or experience adverse events following treatment with a TNF inhibitor. In this group of patients, therapeutic options were limited until recently and an established treatment approach was to switch from one TNF inhibitor to another. In recent years, therapeutic options in these patients have increased with the introduction of biologic agents with novel mechanisms of action, such as rituximab and abatacept. This review outlines the current evidence in support of the available treatment strategies in patients with an inadequate response or intolerance to an initial TNF inhibitor.

Perniok A, Rubbert-Roth A. · Klinikum der Universität zu Köln, Klinik und Poliklinik für Innere Medizin II, Joseph-Stelzmann-Strasse 9, 50931 Köln, Germany. · Z Rheumatol. · Pubmed #14579030 No free full text.

Abstract: After approval of TNF and interleukin-1 inhibiting agents for treatment of refractory rheumathoid arthritis, new agents inhibiting interleukin-6 and costimulatory pathways are entering clinical phase I and II trials. Blockade of costimulation by using a CTLA4 immunoglobulin fusion protein (CTLA4Ig), which inhibits the interaction between CD 28 and CD80/86, has been studied in humans and was demonstrated to be well tolerated and efficacious. A monoclonal antibody to the IL-6 receptor (MRA) blocks bioactivity of IL-6 and also showed favorable effects in first clinical trials. Drug safety data on both substances revealed no severe toxicity or increased incidence of severe infections. For the first time combinations of biological substances like CTLA4Ig and etanercept were demonstrated to be effective and showed no evidence for an increased rate of severe infectious complications. Encouraged by data on these two agents there is substancial hope for a broadened therapeutic armentarium of biological agents in refractory rheumatoid arthritis.

Rubbert-Roth A, Perniok A. · Med. Klinik I der Universität zu Köln, Joseph-Stelzmann-Str. 9, 50924 Köln, Germany. · Z Rheumatol. · Pubmed #12928941 No free full text.

Abstract: New treatment strategies in rheumatoid arthritis are targeted to interfere with critical mediators of inflammation. Proinflammatory cytokines like IL-1 beta and TNFalpha play a crucial role in induction and maintenance of synovitis, pannus formation and bone and cartilage destruction. Within a few years, these morphological changes may lead to joint destruction and consecutively to functional impairment.Since April 2002 a recombinant human interleukin-1 receptor antagonist (Anakinra) is available in Germany for treatment of patients with rheumatoid arthritis. Anakinra (Kineret(R)) is approved for therapy in combination with methotrexate and should be applied according to guidelines established by the German Rheumatology Society for the use of biologicals in treatment of patients with rheumatoid arthritis.The approval of anakinra as a new therapeutic is based on data obtained in large multicenter, placebo-controlled, and randomised trials in comparison to placebo. Treatment of Anakinra as monotherapy or in combination with methotrexate lead to significant improvement of signs and symptoms of disease as measured by the ACR 20 (or more) response and was associated with a slower radiographic progression with regard to joint space narrowing and development of erosions. Anakinra showed a favourable safety profile with injection side reactions as the predominant side effect that occurs in 70% of patients usually after 10-12 days of treatment and that are mostly mild to moderate and self-limiting. Patients with previous pneumonia or other risk factors for pulmonary infections such as chronic obstructive lung disease seem to show a slightly increased risk of developing infectious complications of the bronchopulmonary system while being on anakinra and should be monitored appropriately. Combining IL-1ra treatment with the use of anti-TNF agents showed an increased risk of infectious complications in clinical studies and is not recommended at present. Studies are currently assessing the use of anakinra for treatment of other rheumatic diseases like psoriatic arthritis, juvenile arthritis or spondylarthropathy.

Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R, Anonymous00025. · Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. · Lancet. · Pubmed #18358926 No free full text.

Abstract: BACKGROUND: Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis. METHODS: In this double-blind, randomised, placebo-controlled, parallel group phase III study, 623 patients with moderate to severe active rheumatoid arthritis were randomly assigned with an interactive voice response system, stratified by site with a randomisation list provided by the study sponsor, to receive tocilizumab 8 mg/kg (n=205), tocilizumab 4 mg/kg (214), or placebo (204) intravenously every 4 weeks, with methotrexate at stable pre-study doses (10-25 mg/week). Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20% improvement in both swollen and tender joint counts. The primary endpoint was the proportion of patients with 20% improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria (ACR20 response) at week 24. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00106548. FINDINGS: The intention-to-treat analysis population consisted of 622 patients: one patient in the 4 mg/kg group did not receive study treatment and was thus excluded. At 24 weeks, ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo (120 [59%] patients in the 8 mg/kg group, 102 [48%] in the 4 mg/kg group, 54 [26%] in the placebo group; odds ratio 4.0 [95% CI 2.6-6.1], p<0.0001 for 8 mg/kg vs placebo; and 2.6 [1.7-3.9], p<0.0001 for 4 mg/kg vs placebo). More people receiving tocilizumab than those receiving placebo had at least one adverse event (143 [69%] in the 8 mg/kg group; 151 [71%] in the 4 mg/kg group; 129 [63%] in the placebo group). The most common serious adverse events were serious infections or infestations, reported by six patients in the 8 mg/kg group, three in the 4 mg/kg group, and two in the placebo group. INTERPRETATION: Tocilizumab could be an effective therapeutic approach in patients with moderate to severe active rheumatoid arthritis. FUNDING: F Hoffmann-La Roche, Chugai Pharmaceutical.

Rubbert-Roth A, Burmester G, Anonymous00026. · Universitätsklinikum Köln, Joseph-Stelzmann-Strasse 9, 50924, Köln. · Z Rheumatol. · Pubmed #18830700 No free full text.

This publication has no abstract.

Rubbert-Roth A. · Medizinische Klinik I der Universität zu Köln. · Dtsch Med Wochenschr. · Pubmed #16118736 No free full text.

This publication has no abstract.