Rheumatoid Arthritis: Heller JE

Heller JE, Shadick NA. · Division of Rheumatology, Immunology and Allergy, Brigham & Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. · Curr Opin Rheumatol. · Pubmed #17278922 No free full text.

Abstract: PURPOSE OF REVIEW: As biologics have improved the prognosis for rheumatoid arthritis, the prioritization of outcomes has shifted. Methods of quantifying concerns of particular importance to patients as a basis for better addressing the patient perspective in treatment are being developed. This review aims first to highlight some of the recent research in more traditional outcomes and then to focus on the rapid development of patient-centered outcomes over the last several years. RECENT FINDINGS: Clinical trials with combinations of biologics and other disease-modifying antirheumatic drugs have reported significant improvement in radiographs, inflammatory markers and joint exams in rheumatoid arthritis patients. Concomitantly, several studies have appeared in major journals, reporting that patients are emphasizing outcomes such as fatigue, return to normalcy and mental health that are less easily measured by the traditional outcomes markers. SUMMARY: Recent studies have shown both that rheumatologist and patient approaches to achieving wellness differ and providing patients with a sense of control in reaching that state of wellness leads to better outcomes. Current research is focused on evaluating how best to measure the patient assessments and incorporate the patient voice into the clinic.

Benito-Garcia E, Heller JE, Chibnik LB, Maher NE, Matthews HM, Bilics JA, Weinblatt ME, Shadick NA. · Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. · J Rheumatol. · Pubmed #16821266 No free full text.

Abstract: OBJECTIVE: Methylxanthines, like caffeine, have been thought to reverse the antiinflammatory effects of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated whether patients with RA taking MTX with a higher dietary caffeine intake have a worse clinical response to MTX than those with a lower intake. METHODS: Patients with RA enrolled in a prospective cohort study and currently taking MTX were divided equally into low, moderate, and high caffeine consumers. MTX clinical response was defined by the Disease Activity Score (DAS)28, Multidimensional Health Assessment Questionnaire (MDHAQ) score, and duration of morning stiffness. Regression models were used to study the relationship between caffeine intake and MTX response adjusting for age, sex, and other relevant variables at study enrollment. RESULTS: Two hundred and sixty-four patients with RA taking MTX had an average caffeine intake of 211.7 mg and average MTX dose of 16.0 mg/wk. The low caffeine group comprised 87 patients, the moderate 86, and the high 91. In 3 multivariate models, there was no statistical difference in MTX efficacy between groups, as measured by DAS28 score, MDHAQ score, and duration of morning stiffness at study enrollment. Moderate and high caffeine group had higher DAS28 scores, physician's global assessment, and swollen joint counts, but differences were not significant. CONCLUSION: Caffeine intake among patients taking high doses of MTX for RA did not affect MTX efficacy and RA disease activity over time.

Shadick NA, Heller JE, Weinblatt ME, Maher NE, Cui J, Ginsburg G, Coblyn J, Anderson R, Solomon DH, Roubenoff R, Parker A. · Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. · Ann Rheum Dis. · Pubmed #17491100 No free full text.

Abstract: BACKGROUND: Certain sequences present in the hypervariable region of human leucocyte antigen (HLA)-DRB1 known as the shared epitope (SE) are hypothesised to increase the risk of rheumatoid arthritis (RA), whereas alleles encoding aspartic acid at position 70 (D70 alleles) may have a protective effect. METHODS: Patient HLA-DRB1 serotypes were assessed and the genotypes encoding the SE motif or the putatively protective D70 motif identified in a large RA cohort. Logistic regression was used to analyse associations of genotype with presence of disease, comorbidities and disease severity, and association between genotype and change in disease activity over time. RESULTS: The 689 patients enrolled had a mean (SD) age of 57.9 (13.7) years and mean (SD) disease duration of 15.3 (12.7) years. In a comparison with 482 ethnicity matched population-based controls, the D70 sequence exerted a strong protective effect (OR = 0.52, p<0.001) that remained significant when the SE at the same locus was accounted for (OR = 0.72, 95% CI 0.60 to 0.86, p<0.001). The SE assessed on all HLA-DRB1 serotypic backgrounds except DR1 was associated with RA susceptibility (additive OR = 2.43, p<0.001). Associations were found between SE and serum levels of rheumatoid factor (p<0.001, with correlation of 0.18) and anti-cyclic citrullinated peptide antibodies (p<0.001, with correlation of 0.25) but not with serum C-reactive protein. CONCLUSION: The D70 allele has a significant protective effect that is mitigated but still significant when the risk effect of the SE at the same locus is taken into account. The presence of the SE on DR4 is associated with greater RA susceptibility and certain disease-activity measures.