Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the world's population. Traditional systemic treatments, including methotrexate, ciclosporin, psoralen plus UVA (PUVA), oral retinoids and fumaric acid esters, are widely used for severe disease and are effective in the short term. Severe psoriasis is a chronic disease and patients and physicians have expressed concerns about possible harm from organ toxicity, such as skin cancer (PUVA), hyperlipidaemia (retinoids), renal (ciclosporin) or hepatotoxicity (methotrexate). Long-term monitoring is required and may not detect early organ damage. The pathophysiology of psoriasis remains to be clarified, but advances toward the understanding of the immunological basis of psoriasis have uncovered the involvement of immunological pathways; for example, the role of tumour necrosis factor (TNF)-alpha, T cell proliferation and T cell activation, and migration to the epidermis. This advancement in knowledge combined with developments in recombinant technologies has led to the development of target-specific therapies. Biological agents are defined as proteins that can be extracted from animal tissue or produced via recombinant DNA technologies and possess pharmacological activity. Adalimumab, alefacept, infliximab, efalizumab and etanercept are examples of biological agents currently used for the treatment of psoriasis. Some of these are also therapy for other autoimmune conditions, such as rheumatoid arthritis and Crohn's disease. These biological agents are effective in psoriasis but raise new safety concerns. Information on the safety of biological agents in conditions such as rheumatoid arthritis and Crohn's disease can not be directly extrapolated to psoriasis. An increased incidence of lymphomas has been postulated to be associated with etanercept, infliximab and adalimumab; serious infections, such as tuberculosis, have also been reported with these three biologicals, all of which target TNF-alpha. Demyelinating disorders, such as multiple sclerosis, have been reported with some biologicals as has congestive heart failure. Alefacept, because of its mechanism of action of lowering the number of active T cells, is associated with low T cell counts. Efalizumab has been associated with thrombocytopenia and haemolytic anaemia. Data on the safety of >2.5 years' continuous treatment with efalizumab are reassuring and a valuable beginning to understanding the role and risk of harm of long-term therapy for a chronic disease. Longer follow-up studies and safety databases, for each of the biologicals used in psoriasis, are needed to ensure both prolonged efficacy and minimal risk of harm.
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PMID:Fulfilling an unmet need in psoriasis : do biologicals hold the key to improved tolerability? 1645 34

Efalizumab is a recombinant humanised IgG1 kappa isotype monoclonal antibody against the CD11a molecule. Efalizumab is approved for the treatment of moderate-to-severe psoriasis and is currently administered as a weekly subcutaneous injection. Throughout October 2005, 19,000 patients were treated with efalizumab. According to the package insert that is based on 2762 subjects, the most common adverse reactions associated with efalizumab are a first dose reaction complex that includes headache, chills, fever, nausea and myalgia within two days following the first two injections. These reactions are dose-level-related in incidence and severity and were largely mild-to-moderate in severity when a conditioning dose of 0.7 mg/kg was used as the first dose. Adverse events occurring at a rate between 1 and 2% greater in the efalizumab group compared with placebo were arthralgia, asthenia, peripheral oedema and psoriasis. Efalizumab is associated with a rebound flare reaction in approximately 5% of patients when therapy is ceased. Antiefalizumab antibodies develop in approximately 5% of the subjects who were treated with efalizumab, but the clinical significance of these antibodies is unclear. Efalizumab has rare but serious haematological side effects. Immune-mediated thrombocytopenia platelet counts at or below 52,000 cells/microl have been observed in 0.3% of cases and monitoring of platelet counts monthly for the first 3 months of use and each 3 months thereafter. Reports of four cases of haemolytic anaemia diagnosed four to six months after patients started on the monoclonal antibody exist. Infrequent new onset or recurrent severe arthritis events, including psoriatic arthritis events, have been reported in clinical trials and postmarketing surveillance. Symptoms associated with a hypersensitivity reaction (e.g., dyspnoea, asthma, urticaria, angioedema, maculopapular rash) were rarely noted in the first 12 weeks of the controlled clinical studies. The overall incidence of malignancies of any kind was 1.8 per 100 patient-years for efalizumab-treated patients compared with 1.6 per 100 patient-years for placebo-treated patients. One case each of the following serious adverse reactions was observed: transverse myelitis, bronchiolitis obliterans, aseptic meningitis, idiopathic hepatitis, sialedenitis and sensorineural hearing loss. In the complete safety data from both controlled and uncontrolled studies, the overall incidence of hospitalis ation for infections was 1.6 per 100 patient-years for efalizumab-treated patients compared with 1.2 per 100 patient-years for placebo-treated patients. The rate of infection was 26% in the control group and 29% in treated cases. The most common findings on laboratory assessments in patients using efalizumab were reversible increases in lymphocyte count and total white blood cell. Efalizumab is a safe, effective, but expensive treatment for psoriasis.
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PMID:Efalizumab: a review of events reported during clinical trials and side effects. 1650 42

Psoriasis is a chronic disease that has a very negative impact on the quality of life of those suffering it. Therefore, treatments that make it possible to satisfactorily control the disease in the long term and maintain a good safety profile are needed. Efalizumab fulfills both requirements. In this article, the potential risks involved in treatment with efalizumab, specifically the acute flu-like syndrome, alterations in laboratory data (leukocytosis, lymphocytosis, thrombocytopenia, hemolytic anemia, elevation of alkaline phosphatase and hepatic biochemistry), infections, neoplasms, skin disorders related with psoriasis (localized papular rash, generalized inflammatory rash, changes in the morphology of psoriasis, rebound phenomenon), joint manifestations, acute inflammatory polyradiculoneuropathy and hypersensitivity reactions are reviewed. The contraindications, presence of antiefalizumab antibodies, their drug interactions, use of vaccines and relationship with pregnancy and breast-feeding are also discussed. An adequate selection of the patient, detailed information to the patient on the benefits and risks and correct knowledge of the potential adverse effects by the clinician are essential requirements for satisfactory use of efalizumab in long-term continued therapy.
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PMID:[Is efalizumab a safe treatment for a chronic disease?]. 1834 50