Association of anemia and physical disability among patients with rheumatoid arthritis

OBJECTIVE: To evaluate the relationship between hemoglobin concentration and physical disability in patients with rheumatoid arthritis (RA). METHODS: Data were derived from 2495 patients with RA enrolled in 3 clinical trials (ATTRACT, ASPIRE, and START) and treated with infliximab (3 to 10 mg/kg) plus methotrexate (MTX), or MTX plus placebo. The association of hemoglobin and the Health Assessment Questionnaire (HAQ) score was assessed at baseline (n = 2471) and Week 22 (n = 2458) by Spearman correlation, and multivariate linear regression models were employed to control for confounding effects from demographic and other clinical variables. A logistic regression model was used to estimate the odds ratio (OR) for a clinically meaningful improvement (> or = 0.25 point increase) in HAQ associated with a > or = 1 g/dl improvement in hemoglobin from baseline at Week 22. RESULTS: About 37% of patients with RA had anemia based on World Health Organization criteria: hemoglobin < 12 g/dl in women (39%) and < 13 g/dl in men (32%). Low hemoglobin level was significantly associated with more severe physical disability at baseline (p < 0.001), and both male and female patients with anemia had more severe disability at baseline. Improvement in hemoglobin after treatment at Week 22 was an independent contributor to improvement in HAQ, and a > or = 1 g/dl improvement in hemoglobin after treatment was associated with a clinically meaningful improvement in the HAQ score at Week 22 (OR 1.43, 95% CI 1.10-1.86; p < 0.01). CONCLUSION: Anemia is one of the independent factors contributing to physical disability in patients with RA. Improvement in anemia following effective RA treatment may play an independent role in improving physical function.     

Economic consequences of established rheumatoid arthritis and its treatment

Recent years have witnessed tremendous progress in the therapeutic approach to rheumatoid arthritis (RA). The introduction of novel biologic agents, in particular TNF inhibitors, has allowed clinicians to achieve improved outcomes for their patients. An important factor that has affected the utilization of novel therapies is their acquisition costs, which far exceed those for older antirheumatic drugs. Nevertheless, RA is a serious chronic condition which can cause substantial morbidity and even accelerated mortality for affected individuals. The notable sequelae of uncontrolled rheumatoid synovitis include joint damage and functional disability, which in turn, cause severe economic consequences not only to patients and their families, but also to society. Therefore, it is appropriate for pharmacoceconomic analyses to take into account all relevant costs, not only of the treatments, but of the disease itself. In this way, the value of therapies can be correctly estimated.     

Therapeutic action and underlying mechanisms of a combination of two pentacyclic triterpenes, α- and β-amyrin,in a mouse model of colitis

Background and purpose:

α- and β-amyrin are pentacyclic triterpenes found in plants and are known to exhibit pronounced anti-inflammatory effects. Here, we evaluated the effects of a 1:1 mixture of α- and β-amyrin (α,β-amyrin) on an experimental model of colitis in mice.

Experimental approach:

Colitis was induced in Swiss male mice by trinitrobenzene sulphonic acid (TNBS) and followed up to 72 h; animals were treated systemically with α,β-amyrin, dexamethasone or vehicle. Macro- and microscopic damage, myeloperoxidase activity and cytokine levels were assessed in colons. Histological sections were immunostained for cyclooxygenase-2 (COX-2), vascular endothelial growth factor, phospho-p65 nuclear factor-κB (NF-κB) and phospho-cyclic AMP response element-binding protein (CREB)

Key results:

TNBS-induced colitis was associated with tissue damage, neutrophil infiltration and time-dependent increase of inflammatory mediators. Treatment with α,β-amyrin (3 mg·kg⁻¹, i.p.) or dexamethasone (1 mg·kg⁻¹, s.c.) consistently improved tissue damage scores and abolished polymorphonuclear cell infiltration. α,β-Amyrin, like dexamethasone, significantly diminished interleukin (IL)-1β levels and partially restored IL-10 levels in colon tissues 72 h after colitis induction, but only α,β-amyrin reduced vascular endothelial growth factor expression by immunohistochemistry. The colonic expression of COX-2 at 24 h and that of phospho-NF-κB and phospho-CREB (peaking at 6 h) after colitis induction were consistently inhibited by both α,β-amyrin and dexamethasone.

Conclusions and implications:

Systemic administration of α,β-amyrin exerted a marked and rapid inhibition of TNBS-induced colitis, related to the local suppression of inflammatory cytokines and COX-2 levels, possibly via inhibition of NF-κB and CREB-signalling pathways. Taken together, our data suggest a potential use of α,β-amyrin to control inflammatory responses in bowel disease.     

Interleukin-6 inhibition and clinical efficacy in rheumatoid arthritis treatment--data from randomized clinical trials

Interleukin 6 (IL-6), a pleiotropic cytokine with numerous and varied effects on the inflammatory cascade and immune response, appears to be an attractive target for novel immunomodulatory therapy for systemic inflammatory autoimmune diseases. Proof of principal for this approach has come from studies of the anti-IL-6 receptor monoclonal antibody, tocilizumab. Tocilizumab has been assessed in a number of studies in recent years, mainly in patients with rheumatoid arthritis (RA). Data from randomized controlled clinical trials demonstrate the efficacy of tocilizumab in improving the signs and symptoms of RA. In addition, it appears that such inhibition of IL-6 can have positive effects on functional status, an important outcome for RA patients. Finally, data suggest that treatment with this agent may also inhibit the progression of disease as assessed radiographically. Data from studies currently underway will help refine the ultimate use of this novel approach to treatment, and help clinicians optimize therapy using this approach.     

Value of the Routine Assessment of Patient Index Data 3 in Patients With Psoriatic Arthritis: Results From a Tight‐Control Clinical Trial and an Observational Cohort

Objective

To analyze the Routine Assessment of Patient Index Data 3 (RAPID3), a patient‐reported, composite index, designed initially for feasibility in clinical care. RAPID3 was developed in rheumatoid arthritis, but has been found useful in many rheumatic diseases. We analyzed RAPID3 in patients with psoriatic arthritis (PsA).

Methods

Post hoc analyses were performed on 2 independent data sets, the Tight Control of Psoriatic Arthritis (TICOPA) clinical trial, and the Long‐Term Outcome in Psoriatic Arthritis Study (LOPAS II), an observational cohort. RAPID3 (range 0–30) is the total of three 0–10 scores for the Health Assessment Questionnaire disability index (recalculated from 0–3), pain visual analog scale (VAS), and global VAS. RAPID3 scores were compared to the Psoriatic Arthritis Disease Activity Score (PASDAS), the Disease Activity in Psoriatic Arthritis (DAPSA), and other available clinical measures, according to Spearman's correlation coefficients, standardized response mean, SEM, smallest detectible difference, minimally important difference (in patients who improved), and receiver operating characteristic curves. RAPID3 remission was compared to criteria for both standard minimal disease activity (MDA) and very low disease activity (VLDA).

Results

RAPID3 was correlated significantly with PASDAS in TICOPA (r = 0.79, P < 0.01) and with DAPSA in LOPAS II (ρ = 0.59, P < 0.01), and with most other measures in both data sets. RAPID3 discriminated between tight control and standard care in TICOPA at 48 weeks at levels comparable to DAPSA and the PASDAS (P < 0.01). RAPID3 remission discriminated treatment groups in TICOPA intermediate between MDA and VLDA criteria.

Conclusion

RAPID3 appears comparably informative to PASDAS and DAPSA in PsA, with greater feasibility for routine clinical care.