Response of elderly patients with rheumatoid arthritis to methotrexate or TNF inhibitors compared with younger patients.

OBJECTIVE: To compare the efficacy of MTX and MTX+TNF inhibitors (TNFis) in elderly patients with RA with that in patients of younger age. METHODS: Data from two large, randomized, controlled, double-blind trials in patients with early RA using adalimumab or infliximab+MTX or MTX alone were obtained and pooled. Composite disease activity indices were calculated at baseline and 1 year of treatment, and compared in groups of patients classified by quartiles of age with the highest age group comprising 61-82 years using analysis of variance or Kruskal-Wallis test. RESULTS: Across all age quartiles, improvement on MTX was similar with respect to changes of composite disease activity indices, assessment of physical function and X-ray progression. Likewise, TNFi+MTX had similar effects across all age groups, but the effects of the combination were more profound than those of MTX monotherapy. Also in 10% of the patients with the highest age, primarily septuagenarians, improvement was seen to a similar degree as in the younger ones. CONCLUSIONS: Responsiveness of elderly patients with RA to MTX or TNFi+MTX is similar to that observed in patients of younger age.

Abatacept: the evidence for its place in the treatment of rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is the most common inflammatory joint disease in adults with a prevalence of 0.5-1%. The development of targeted therapies, especially anti-TNF (tumor necrosis factor) treatment, has improved disease outcome during the last decade. But despite this progress 25-30% of patients still show unsatisfactory response. Abatacept is a costimulation blocker that inhibits T-cell activation and interrupts the process that leads to inflammation in RA. AIMS: The purpose of this article is to review the clinical trials of abatacept and to discuss how it will fit into the treatment of RA. The medical literature was reviewed for appropriate articles and 123 articles have been identified containing the search terms "abatacept OR CTLA4-Ig AND rheumatoid." All clinical trials were reviewed with respect to clinical and radiologic outcome, quality of life, and safety of patients with RA receiving abatacept therapy. EVIDENCE REVIEW: There are seven (phase II or phase III) clinical trials that have clearly demonstrated efficacy and safety of this new drug. Furthermore, radiographic data show that abatacept also inhibits the progression of joint destruction, one of the important burdens of RA. Abatacept can be used concomitantly with conventional disease-modifying antirheumatic drugs or as monotherapy. Due to an increased risk of infections and malignancies but without an important enhancement of efficacy, simultaneous treatment with abatacept and other biologic response modifiers is not recommended. PLACE IN THERAPY: With its different mechanism of action, abatacept may be an alternative therapy for patients with an inadequate response to other arthritis therapies, especially for those patients with RA refractory to anti-TNF treatment. Cost effectiveness is dependent on underlying disease progression.

Targeted therapy in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is the most common inflammatory joint disease in adults leading to pain and disability. New drugs, called biologicals, have opened up new possibilities in the treatment of RA. OBJECTIVE: Targeting pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α) or interleukin-1 (IL-1) is well established in clinical care of RA patients. However, lack or loss of clinical response occurs in up to 25% of the patients. New strategies beyond these targets, namely blocking T cells by abatacept or B cells by rituximab (RTX), have been introduced recently. METHODS: All relevant clinical trials published in peer-reviewed journals are discussed in this article. Data from abstracts presented at congresses have not been included. CONCLUSION: TNF blocking agents have significantly improved therapy of and outcome in RA patients and, therefore, are still the first choice biologicals for the treatment of RA. Alternatively, abatacept or RTX offer new options in case of inefficacy of or contraindications against anti-TNF therapy. Forthcoming drugs, such as tocilizumab, will extend our armamentarium to treat RA effectively.

The public neglect of rheumatic diseases: insights from analyses of attendees in a musculoskeletal disease awareness activity.

OBJECTIVES: To obtain data on the care received by individuals counselled during a public health awareness campaign on painful musculoskeletal conditions (MSC). METHODS: Easy non-formal access to rheumatologists/pain specialists was offered using a mobile unit (Rheuma-Bus) at widely accessible sites. Clients were asked to assess their severity of pain using a 100 mm visual analogue scale (VAS). Age, gender, disease duration, diagnosis if known, current and previous treatment as well as tentative diagnoses assigned and recommendations given to each individual by the counselling physicians were recorded. RESULTS: Average (SD) VAS pain rating was 59 (20.6) mm. Approximately 40% of clients had never consulted a physician for their condition before, but had lower pain scores than those who had seen a physician. Patients with inflammatory MSC had higher pain scores than those with non-inflammatory conditions. More than 2% of the clients had a newly detected inflammatory rheumatic disease. CONCLUSIONS: Many individuals having painful MSC seek medical help only when a very high threshold of pain is reached. Even while under treatment, the high mean pain scores suggest neglect of MSC that are not adequately recognised as important contributors to disability and decreased quality of life.

Targeted therapy in rheumatoid arthritis.

The approach of targeting cytokines has dramatically improved the success in the treatment of rheumatoid arthritis (RA). The blocking of tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 is well established in clinical practice, but a lack or loss of clinical response still occurs in up to 30% of RA patients. Therefore, enhanced efforts must be made to develop new strategies to disrupt the inflammatory process and to inhibit synovitis and joint destruction. In this respect, the blocking of IL-6 receptor with tocilizumab, the prevention of costimulatory T cell signals by abatacept, or targeting B cells with rituximab look promising in clinical trials. Furthermore, blocking intracellular signal transduction broadens the spectrum of targeted therapy. This article reviews recent clinical aspects of established anti-cytokine therapies and gives an insight into the experimental and clinical development of new specifically acting drugs.