Clinical considerations of hyaluronidase as an adjunct to subcutaneous rituximab injection.

Subcutaneous rituximab injectables are formulated with recombinant human hyaluronidase as an adjunct to facilitate the absorption of the large volume of rituximab. We review the clinical considerations regarding the potential for systemic hyaluronidase toxicity and increased systemic absorption of subcutaneous or topical drugs administered subsequent to rituximab.

Use of hematopoietic growth factors as adjuvant therapy for anemia and neutropenia in the treatment of hepatitis C.

OBJECTIVE: To review the hematologic adverse effects of hepatitis C virus (HCV) therapy and adjuvant treatment with epoetin alfa and granulocyte colony-stimulating factor (ie, filgrastim). DATA SOURCES: Medical literature indexed in MEDLINE (1966-January 2007) and EMBASE (1980-January 2007) was searched, and published conference abstracts were reviewed. STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed articles and relevant conference abstracts regarding the use of epoetin alfa and granulocyte colony-stimulating factor were reviewed. DATA SYNTHESIS: Ribavirin induces a dose-dependent hemolytic anemia. Studies using epoetin alfa 40 000 units subcutaneously once weekly have demonstrated efficacy in maintaining hemoglobin, ribavirin dose, and quality of life scores, but clear benefit shown with sustained virologic response (SVR) is lacking. The hemoglobin threshold for initiation of epoetin alfa used in studies may not adequately reflect values used in clinical practice. Treatment-related neutropenia is caused primarily by interferon or peginterferon. Few studies have investigated the impact of granulocyte or granulocyte-macrophage colony-stimulating factor derivatives on neutropenia. Results of dose maintenance evaluation vary, and studies reporting data on SVR showed no effect from growth factor therapy. The frequency of bacterial infections was not reported. CONCLUSIONS: The role and benefit of hematopoietic growth factors in HCV therapy have not been conclusively determined to date. However, the possibility of a benefit to individual patients seen on an outpatient basis remains, and an individualized treatment approach is recommended.

Cost-effectiveness of tumor necrosis factor-alpha antagonists in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

The treatment of chronic arthritic diseases has undergone some dramatic changes over the past few years. In particular, a new class of drugs called the tumor necrosis factor-alpha antagonists has transformed the management of rheumatoid arthritis, and decision makers are now consid1ering their use in psoriatic arthritis and ankylosing spondylitis. Whilst short-term clinical trials suggest that tumor necrosis factor-alpha antagonists improve physical function and pain linked to disease activity, this class of drug has generated controversy owing to its substantial cost. Pharmacoeconomic studies conclude that tumor necrosis factor-alpha antagonists result in significant increases in health-related quality of life; however, the cost-effectiveness of this class of drug remains uncertain, particularly in the treatment of psoriatic arthritis and ankylosing spondylitis. This paper reviews pharmacoeconomic analyses examining the cost-effectiveness of tumor necrosis factor-alpha inhibitors in rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis.

Management of anemia in erythropoietin-resistant hemodialysis patients.

BACKGROUND: Human recombinant erythropoietin (rHuEPO) is administered to patients with end-stage renal disease for treatment of anemia. OBJECTIVE: To assess the impact of a structured team approach to anemia management in rHuEPO-resistant hemodialysis patients. METHODS: This was an 8-month prospective, open-label, quality-improvement initiative. Nineteen patients in a 160-bed hemodialysis unit receiving rHuEPO doses >300 units/kg/wk were defined as rHuEPO-resistant. Hemoglobin (Hb), iron indices, parathyroid hormone, folate, B12, aluminum, and reticulocyte counts were determined at baseline. The former 3 parameters were followed every 6, 12, and 26 weeks, respectively. Vascular access flow was regularly assessed via ultrasonic dilution methodology. Target Hb was 12.0-13.5 g/dL. All factors potentially contributing to rHuEPO resistance were assessed and, if possible, treated every 6 weeks by a dedicated anemia team. Downward rHuEPO dosage adjustments of 12.5-25% to the closest 1000 units were considered if underlying causes of rHuEPO resistance could not be identified or reversed, or if the Hb rose beyond the target level. RESULTS: Dysfunctional vascular access and iron deficiency were the predominant treatable factors associated with rHuEPO resistance. At 8 months, mean rHuEPO dosage decreased significantly from 469 to 319 units/kg/wk (p < 0.001) and mean Hb increased significantly from 10.6 to 11.6 g/dL (p = 0.023). Eight-month cost savings approximated $45 000 (CDN$). CONCLUSIONS: A structured team approach to the management of rHuEPO-resistant patients was successful in significantly lowering rHuEPO dosage with improvement in serum Hb at a substantial cost savings.