Reiter's syndrome is an acute inflammatory arthritis with no standard treatment options for patients unresponsive to nonsteroidal antiinflammatory drugs (NSAID). In patients positive for human ...immunodeficiency virus (HIV), HIV-RNA levels have been correlated with elevated tumor necrosis factor-alpha (TNF-alpha) levels. We investigated the safety and activity of infliximab, an anti-TNF-alpha chimeric monoclonal antibody, in the treatment of an HIV positive patient with Reiter's refractory to NSAID therapy. A 41-year-old HIV positive man with Reiter's syndrome was treated with infliximab 300 mg intravenously at Weeks 0, 2, and 6 and then every 6 to 7 weeks thereafter. He presented with severe fatigue, pain, muscle wasting, synovitis of the elbows, wrists and knees, a scaly rash in the groin area, burning during urination, and severe onycholysis on all digits. Laboratory assessment revealed hemoglobin 7.8 g/dl, erythrocyte sedimentation rate (ESR) 152 mm/h, white blood cell count 5700 cells/mm3, and C-reactive protein (CRP) 65.7 mg/dl. HIV viral load on presentation was 1600 quantitative:ultrasensitive (Qn:US) copies/ml, decreased from a maximum of 428,000 Qn:US copies/ml at the start of antiretroviral therapy. After 6 months taking infliximab, all complaints resolved, nails regrew, and the rash cleared. CRP decreased to 0.8 mg/dl and ESR to 22 mm/h. During this 6 month period antiretroviral therapy remained unchanged, and the viral titer remained below 400 Qn:US copies/ml.
Objective. To assess the efficacy and safety profiles of two different rituximab retreatment regimens in patients with RA.
Methods. Four hundred and ninety-three RA patients with an inadequate ...response to MTX recruited into rituximab Phase II/III studies received further courses of open-label rituximab based on two approaches: (i) treatment to target (TT): patients assessed 24 weeks after each course and retreated if not in remission DAS in 28 joints based on ESR (DAS-28-ESR) 2.6; (ii) treatment as needed (PRN): patients retreated at the physician's discretion 24 weeks following the first course and 16 weeks following further courses, if both swollen and tender joint counts were 8. All courses consisted of i.v. rituximab 2 × 1000 mg 2 weeks apart plus MTX. Observed data were analysed according to treatment strategy.
Results. Multiple courses of rituximab maintained or improved responses irrespective of regimen. TT provided tighter control of disease activity with significantly greater improvements in DAS-28-ESR and lower HAQ-disability index scores vs PRN. TT resulted in significantly more patients achieving major clinical response. PRN resulted in recurrence of disease symptoms between courses, with TT significantly reducing the incidence of RA flares. Despite more frequent retreatment with TT compared with PRN, the rates of serious adverse events and serious infections were comparable between regimens.
Conclusions. Retreatment with rituximab based on 24-week evaluations and to a target of DAS-28-ESR remission leads to improved efficacy and tighter control of disease activity compared with PRN without a compromised safety profile. TT may be the preferable rituximab treatment regimen for patients with RA.
Objective: To incorporate a new trial design to examine clinical response, cytokine expression and joint imaging in patients with rheumatoid arthritis (RA) switching from etanercept to infliximab ...treatment. Methods: A randomised, open-label, clinical trial of 28 patients with an inadequate response to etanercept was conducted. Eligible patients received background methotrexate and were randomised 1:1 to discontinue etanercept and receive infliximab 3 mg/kg at weeks 0, 2, 6, 14 and 22, or to continue etanercept 25 mg twice weekly. Data were analysed for clinical response, serum biomarker levels, radiographic progression, MRI and adverse events. Results: At week 16, 62% of infliximab-treated patients achieved American College of Rheumatology 20% criteria for improvement in RA (ACR20) responses compared with 29% of etanercept-treated patients. A 30.8% decrease from baseline in Disease Activity Score 28 was observed in patients receiving infliximab, compared with a 16.0% decrease in patients receiving etanercept. ACR20 and American College of Rheumatology 50% criteria for improvement in RA responses correlated at least minimally with intracellular adhesion molecule-1 and interleukin 8 in patients receiving infliximab. 38% of patients who were switched to infliximab showed reductions in Health Assessment Questionnaire scores (>0.4), compared with 0% of patients receiving etanercept. MRI analyses were inconclusive. Both drugs were well tolerated; 54% of infliximab-treated patients and 50% of etanercept-treated patients reported adverse events. Conclusions: In this exploratory, open-label trial (with single-blind evaluator), patients were randomised to continue with etanercept or switch to infliximab. The small sample size of this hypothesis-generating study was underpowered to show statistical differences between groups. There was a numerical trend favouring patients who switched to infliximab, therefore warranting further study with a more rigorous design.
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