Association between anti-TNF-α therapy and all-cause mortality.

PURPOSE: To compare mortality among patients with selected autoimmune diseases treated with anti-tumor necrosis factor alpha (TNF-α) agents with similar patients treated with non-biologic therapies. METHODS: Cohort study set within several large health care programs, 1998-2007. Autoimmune disease patients were identified using diagnoses from computerized healthcare data. Use of anti-TNF-α agents and comparison of non-biologic therapies were identified from pharmacy data, and mortality was identified from vital records and other sources. We compared new users of anti-TNF-α agents to new users of non-biologic therapies using propensity scores and Cox proportional hazards analysis to adjust for baseline differences. We also made head-to-head comparisons among anti-TNF-α agents. RESULTS: Among the 46 424 persons included in the analysis, 2924 (6.3%) had died by the end of follow-up, including 1754 (6.1%) of the 28 941 with a dispensing of anti-TNF-α agent and 1170 (6.7%) of the 17 483 who used non-biologic treatment alone. Compared to use of non-biologic therapies, use of anti-TNF-α therapy was not associated with an increased mortality in patients with rheumatoid arthritis (adjusted hazard ratio [aHR] 0.93 with 95% confidence intervals (CI) 0.85-1.03); psoriasis, psoriatic arthritis, or ankylosing spondylitis (combined aHR 0.81 with CI 0.61-1.06; or inflammatory bowel disease (aHR 1.12 with CI 0.85-1.46). Mortality rates did not differ to an important degree between patients treated with etanercept, adalimumab, or infliximab. CONCLUSION: Anti-TNF-α therapy was not associated with increased mortality among patients with autoimmune diseases.

Plasmapheresis therapy for rare but potentially fatal reaction to rituximab.

Rituximab (Rituxan), a genetically engineered chimeric murine and human IgG1 monoclonal antibody directed against CD20 antigen, is an emerging drug used for a wide spectrum of disease processes and found to be relatively safe. We report a near-fatal reaction to rituximab, which started 30 min after infusion and worsened over 24 to 48 h, resulting in hemodynamic and respiratory compromise that necessitated both intubation and high-dose vasopressors. Subsequent treatment with plasmapheresis helped stabilize and improve the patient's clinical condition, and the patient was discharged home on hospital day 5. There is no specific treatment for these severe and sometimes fatal reactions except supportive care with plasmapheresis. With the increased use of rituximab therapy in the medical management of numerous diseases, those in the medical community need to be cognizant of the rare fatal or near-fatal infusion reaction and the benefit that may accrue from plasmapheresis therapy.

Trastuzumab in the treatment of metastatic breast cancer : anticancer therapy versus cardiotoxicity.

Trastuzumab, a monoclonal antibody against the HER2 receptor, was recently approved for the treatment of metastatic breast cancer. However, 28% of patients receiving both an anthracycline and trastuzumab developed heart failure. Although HER2 overexpression has been associated with the development of cancer, HER2 receptors seem to be cardioprotective because they mediate the activation of important cardiac survival pathways. Because the morbidity and mortality of heart failure surpasses that of many cancers, prudent medical practice mandates that physicians learn more about the mechanisms of trastuzumab-induced cardiotoxicity and develop algorithms for assessing risk/benefit ratios before extending the use of this agent to patients with less invasive forms of breast cancer.

Anti-CD3-enhanced interleukin-2 immunotherapy of pulmonary metastases.

UNLABELLED: A newly developed monoclonal rat IgG 2b antibody which in vitro can activate both helper and cytolytic T-lymphocytes by binding to the CD3 epsilon subunit of the T-cell receptor complex was tested alone and in combination with Interleukin-2, a growth factor for activated T-cells, for ability to reduce established pulmonary metastases in a murine model. C57BL/6 mice injected iv with a tumor cell suspension of a weakly immunogenic fibrosarcoma, MCA106, were randomly assigned to 1 of 15 treatment groups for intraperitoneal injections with YCD3 (0, 0.1, 1, 10, or 100 micrograms) on Days 3, 5, 7, 10, 12, 17, and 19 or with IL-2 (0, 1000, or 50,000 units bid) on Days 3 through 7, 10 through 12, and 17 through 19. On Day 21 all mice were sacrificed for enumeration of metastases. Pooled splenocytes of three randomly selected mice from each group were assayed for surface expressions of T-cell markers Thy-1, Ly2, and L3T4. RESULTS: High-dose IL-2 (50,000 units bid) in combination with low-dose YCD3 (1 microgram) reduced metastases 60% (P less than 0.005). YCD3 or IL-2 alone was ineffective. Combined high-dose IL-2 (50,000 units) and high-dose YCD3 (100 micrograms) resulted in 100% mortality. Phenotypically, YCD3 induced a dose-dependent depletion of T-cells from 25 to 2.4% (0.1 to 100 micrograms, respectively). These results suggest potential clinical applicability of low-dose anti-CD3 monoclonal antibody to enhance antitumor efficacy of high-dose IL-2. However, the toxicity of high-dose anti-CD3 and high-dose IL-2 cautions for care in selection of dose.