Rheumatoid Arthritis: Hooper M

Keystone E, Freundlich B, Schiff M, Li J, Hooper M. · Mount Sinai Hospital, The Rebecca MacDonald Centre for Arthritis and Autoimmunity, Toronto, ON M5G 1X5, Canada. · J Rheumatol. · Pubmed #19228659 No free full text.

Abstract: OBJECTIVE: This analysis examined clinical and radiographic responses to methotrexate (MTX), etanercept (ETN), and combination ETN and MTX in patients with moderate versus severe rheumatoid arthritis (RA) in both early and late disease. METHODS: Data from the Trial of Etanercept and Methotrexate With Radiographic Patient Outcomes (TEMPO) and the Early Rheumatoid Arthritis trials were used. Patients were classified with moderate or severe RA based on Disease Activity Score including 28-joint count (DAS28). Outcomes included DAS28 remission, DAS28 low disease activity, Health Assessment Questionnaire (HAQ), American College of Rheumatology (ACR) scores, Total Sharp Score (TSS) progression, no radiographic progression (annualized change in TSS > or = 0), change from baseline in TSS, and the change in TSS for patients who had radiographic progression (TSS > 0). RESULTS: Patients with moderate disease generally achieved better clinical outcomes than patients with severe disease, including significant differences in DAS28 remission, low disease activity, and HAQ < or =0.5 at Month 12. Patients with baseline severe disease had higher ACR and DAS responses than patients with moderate disease. CONCLUSION: Patients with severe RA disease activity achieved substantial clinical improvement with high-dose MTX and/or ETN treatment, but patients with moderate disease were more likely to reach a lower disease activity state. These findings were independent of disease duration. The results support the opportunity for excellent clinical outcomes, particularly with combination therapy, in patients with moderate RA.

Kavanaugh A, Klareskog L, van der Heijde D, Li J, Freundlich B, Hooper M. · Center for Innovative Therapy, Division of Rheumatology, Allergy, and Immunology, UCSD, San Diego, California, USA. · Ann Rheum Dis. · Pubmed #18535115 links to  free full text

Abstract: BACKGROUND: Whereas many patients respond quickly to treatment with tumour necrosis factor (TNF) inhibitors, some patients may experience significant but delayed responses. OBJECTIVE: To evaluate the clinical response between 12 and 24 weeks in subjects with rheumatoid arthritis from the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes. METHODS: Clinical response was assessed at 24 weeks in 12-week non-responders, according to American College of Rheumatology (ACR) response criteria. The proportion of subjects who successfully maintained response to 52 weeks was analysed, as were radiographic outcomes. RESULTS: Data from 682 subjects were included in the analysis. Non and partial responders in all three groups (etanercept, methotrexate and etanercept plus methotrexate) at week 12 showed an improvement in responses at week 24. Over 80% of the week 24 ACR20/50/70 responders in the etanercept plus methotrexate arm sustained their response to 52 weeks. In the etanercept arms, a delayed clinical response was not associated with increased radiographic progression at week 52. CONCLUSION: A significant proportion of non and partial responders to etanercept with or without methotrexate therapy at week 12 achieved a good clinical response or improved their overall clinical response at week 24. Discontinuing TNF inhibitor therapy at 12 weeks may be premature in some rheumatoid arthritis patients.

Moskowitz RW, Lesko M, Hooper M. · Case Western Reserve University of Medicine, Cleveland, OH, USA. · Semin Arthritis Rheum. · Pubmed #17023256 No free full text.

Abstract: OBJECTIVE: The macrolide family of antibiotics (erythromycin, clarithromycin, and others), have both antimicrobial and immunomodulatory effects. This study explored the effect of clarithromycin on the clinical course of patients with undifferentiated connective tissue disease (UCTD) in a 12-week open-label study. METHODS: The diagnosis of UCTD was based on symptoms/signs of connective tissue disease, and the presence of 1 or more positive autoimmune disease tests, but with insufficient criteria to make a definitive diagnosis. Screening and monthly follow-up visits over 12 weeks included the following: history and physical examination; concurrent medications; the 68/66 tender/swollen joint count; visual analog scores 0 to 100 mm for patient and physician global assessment of disease activity, and patient pain; antinuclear antibody panel, rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, and blood chemistry. RESULTS: Seven patients with rheumatic disease were treated with clarithromycin; 6 of 7 had symptomatic relief. Two subjects treated empirically before the decision to perform an open-label study responded favorably. Four of 5 patients who completed the prospective open-label study had mean maximal improvements from baseline of 78, 75, and 79% in patient pain, patient global, and investigator global assessments, respectively. Pain relief occurred as early as 1 week. Drug withdrawal with rechallenge in 2 patients resulted in flare followed by recapture of symptomatic relief. CONCLUSIONS: Clarithromycin, a macrolide antibiotic, led to clinical improvement in patients with UCTD. Efficacy and safety data support further investigation of macrolide antibiotic use as a primary or adjunctive treatment in various connective tissue diseases.

Hooper M, Kallas EG, Coffin D, Campbell D, Evans TG, Looney RJ. · Department of Medicine, University of Rochester, NY, USA. · J Rheumatol. · Pubmed #10405929 No free full text.

Abstract: OBJECTIVE: Previous researchers have found expansion of CD4+CD28- T cells in patients with rheumatoid arthritis (RA) compared to age matched controls, and have identified expanded clones of autoreactive cells within this population. We examine the association of prior cytomegalovirus (CMV) infection (positive serum anti-CMV IgG) with the percentage of CD4+CD28- T cells and CD8+CD28- T cells in patients with RA. METHODS: A total of 45 patients (36 women, 9 men), mean age of 59 years, with definite RA were studied. RESULTS: In this group 28 patients were seropositive for CMV and 17 seronegative. Seropositive and seronegative subjects did not differ significantly in age, sex, medication use, or severity of disease. Joint count, Health Assessment Questionnaire, pain score, patient global assessment, physician global assessment, and presence of extraarticular disease served to assess disease severity. Expression of CD4/CD28/CD57 and CD8/CD28/CD57 on lymphocytes was determined by 3 color flow cytometry. (CD28 and CD57 are reciprocally related.) CD4+CD28-CD57+ T cells were expanded only in CMV seropositive patients. CONCLUSION: The "carrier" phenotype that has been hypothesized based on a 2 population model for the distribution of CD4+CD28- T cells in RA can be explained by prior infection with CMV.