Treatment with Mycophenolat Mofetil of Steroid-Dependent Asthma—One Case of Severe Asthma

Background. Some patients with severe nonallergic asthma can be difficult to treat with conventional therapy. Mycophenolat Mofetil (MMF) is an immunosuppressive drug with multiple mechanisms. There is theoretical support of specific effect of MMF on severe asthma, in “difficult to treat” patients. The aim of the present case was to explore whether MMF had an effect in one case of severe refractory asthma. The patient. This case deals with one patient with very severe nonallergic treatment refractory asthma who experienced treatment failure on ordinary antiasthmatic treatment and severe adverse events to conventional immunosupressive treatment. She was then treated with MMF. Results. The patient experienced a gain in FEV1 and a reduction in the need for oral glucocorticosteroids as well as seldom need of when needed bronchodilator both during daytime and night. It therefore seems very interesting to examine the use of MMF for severe refractory asthma with further clinical studies and basic cellular trials

An open-label pilot study of the effectiveness of adalimumab in patients with rheumatoid arthritis and previous infliximab treatment: relationship to reasons for failure and anti-infliximab antibody status

This prospective open-label pilot study evaluated the effectiveness and safety of adalimumab and the relationship to antibodies against infliximab (IFX) in adult patients with active rheumatoid arthritis (RA) who had been treated previously with IFX and experienced treatment failure owing to lack or loss of response or intolerance. Patients self-administered adalimumab 40 mg subcutaneously every other week for 16 weeks, followed by maintenance therapy for up to Week 56. Measures of effectiveness included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria, 28-joint Disease Activity Score, and the Health Assessment Questionnaire Disability Index. Serum IFX concentrations, human antichimeric antibody against IFX (HACA), adalimumab serum concentrations, antiadalimumab antibody, and safety also were assessed. Of the 41 enrolled patients, 37 completed 16 weeks and 30 completed 56 weeks of treatment. Patients experienced clinically meaningful improvements in all measures of RA activity, with greater response rates observed for patients who had experienced loss of initial response to or intolerance of IFX. At Week 16, 46% of patients achieved an ACR20 and 28% achieved an ACR50; 61% achieved an at least moderate and 17% achieved a good EULAR response. Clinical benefit was maintained through Week 56 in all effectiveness parameters. Baseline HACA status did not significantly impact effectiveness. No new safety signals were observed; neither former IFX intolerance status nor baseline HACA status had a clinically relevant impact on adverse event frequency or severity. Adalimumab was effective and well-tolerated in patients with RA who previously failed IFX therapy, irrespective of reason for discontinuation and of HACA status

DAS-28-based EULAR response and HAQ improvement in rheumatoid arthritis patients switching between TNF antagonists

<p>Abstract</p> <p>Introduction</p> <p>No definitive data are available regarding the value of switching to an alternative TNF antagonist in rheumatoid arthritis patients who fail to respond to the first one. The aim of this study was to evaluate treatment response in a clinical setting based on HAQ improvement and EULAR response criteria in RA patients who were switched to a second or a third TNF antagonist due to failure with the first one.</p> <p>Methods</p> <p>This was an observational, prospective study of a cohort of 417 RA patients treated with TNF antagonists in three university hospitals in Spain between January 1999 and December 2005. A database was created at the participating centres, with well-defined operational instructions. The main outcome variables were analyzed using parametric or non-parametric tests depending on the level of measurement and distribution of each variable.</p> <p>Results</p> <p>Mean (± SD) DAS-28 on starting the first, second and third TNF antagonist was 5.9 (± 2.0), 5.1 (± 1.5) and 6.1 (± 1.1). At the end of follow-up, it decreased to 3.3 (± 1.6; Δ = -2.6; p > 0.0001), 4.2 (± 1.5; Δ = -1.1; p = 0.0001) and 5.4 (± 1.7; Δ = -0.7; p = 0.06). For the first TNF antagonist, DAS-28-based EULAR response level was good in 42% and moderate in 33% of patients. The second TNF antagonist yielded a good response in 20% and no response in 53% of patients, while the third one yielded a good response in 28% and no response in 72%. Mean baseline HAQ on starting the first, second and third TNF antagonist was 1.61, 1.52 and 1.87, respectively. At the end of follow-up, it decreased to 1.12 (Δ = -0.49; p < 0.0001), 1.31 (Δ = -0.21, p = 0.004) and 1.75 (Δ = -0.12; p = 0.1), respectively. Sixty four percent of patients had a clinically important improvement in HAQ (defined as ≥ -0.22) with the first TNF antagonist and 46% with the second.</p> <p>Conclusion</p> <p>A clinically significant effect size was seen in less than half of RA patients cycling to a second TNF antagonist.</p

Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis.

Cytokines such as tumor necrosis factor (TNF) are expressed at high levels in rheumatoid joint tissue, where they contribute significantly to inflammation and articular destruction. TNF was the first cytokine to be fully validated as a therapeutic target for rheumatoid arthritis (RA). In nearly a decade since anti-TNF agents-such as infliximab, etanercept and adalimumab-were launched as the first biologic therapies to be licensed for RA, much has been learnt about how and when in the disease course this class of drug can be used to achieve optimal therapeutic benefit. Other cytokine targets, such as interleukin (IL)-6 or IL-1, have also been validated and several are in the process of being tested. However, TNF is likely to remain the preferred target of first-line biologic therapy for the foreseeable future as, in populations with active RA despite ongoing, nonbiologic, DMARD therapy, biologic inhibition of either IL-6 or IL-1 demonstrates no obviously superior outcomes to TNF blockade. Furthermore, new approaches to blockade of signaling mediated by bioactive TNF might have the potential to generate higher-magnitude clinical responses than are currently elicited