Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Guidelines for Care Needs a team approach of rheumatologists, dermatologists and patients (NPF, ?AF) Combination of Cost and Evidence Based Criteria will be likely determinants – Some rationing is inevitable. Access to Biologics Fact: Cost determines access – How do we optimize patient care in a cost conscious environment? – How do we prevent inappropriate placement of biologics as last drugs of choice? Role of Methotrexate Rheumatologists think MTX is safe long term for use (RA use predominates); Rheumatologists used biologics first therefore guidelines in place for RA. Dermatologists think MTX is not safe long term and requires stringent monitoring (Psoriasis predominates). Third party payers chose MTX first because of cost. How can we work together to make evidence-based recommendations for PSA and PSO on use of MTX? Liver Toxicity Compared Methotrexate and histologic hepatic abnormalities: a meta-analysis. Whiting-O'Keefe QE, Fye KH, Sack KD. Am J Med. 1991 Jun;90(6):711-6. A meta-analysis of 15 studies (636 patients) examined the relationship between long-term, lowdose methotrexate administration and biopsy evidence of liver fibrosis. The incidence of progression of liver disease (defined as worsening of at least one grade on the histologic classification of Roenigk) among 636 patients was 27.9%. The overall incidence of advanced pathologic changes on liver biopsy (grades IIIB or IV) among 636 patients was 5.0% Whiting-O'Keefe QE, Fye KH, Sack KD. Am J Med. 1991 Jun;90(6):711-6. The rate of progression of liver disease in 15 studies was associated with the cumulative dose of MTX (p= 0.01). Patients on average had a 6.7% chance of progressing at least one histologic grade on liver biopsy for each gram of methotrexate taken. Patients with psoriasis were more likely than patients with rheumatoid arthritis to have – advanced changes (7.7% versus 2.7%, p = 0.003) and – histologic progression (33.1% versus 24.3%, p = 0.02) Whiting-O'Keefe QE, Fye KH, Sack KD. Am J Med. 1991 Jun;90(6):711-6. The risk of liver toxicity in patients undergoing long-term, low-dose methotrexate therapy is substantial, and that risk increases with the total cumulative dose and with heavy consumption of alcohol. Heavy users of alcohol should not receive long-term methotrexate therapy. For most patients who are not heavy users of alcohol, liver biopsies should be done periodically to monitor for the occurrence of liver toxicity. Liver biopsies from psoriatics related to methotrexate therapy. 2. Findings before and after methotexate therapy in 88 patients. A blind study. Nyfors A, Poulsen H Acta Pathol Microbiol Scand [A]. 1976 May;84(3):262-70. 88 patients with severe, recalcitrant psoriasis had liver biopsies performed before and after MTX therapy. MTX was given for an average of 26 months as a single, weekly, oral dose of 25 mg maximum. The mean cumulative dose was 1733 mg (range 175-4590 mg). An increase in the number of pathological post-MTX liver biopsies was found (p < 0.0001). Of the 88 patients 6 developed cirrhosis and another 5 developed fibrosis, during MTX therapy (12.5%). A multifactorial index comprising: cumulative dose of MTX, admitted alcoholic intake during MTX therapy, age, obesity and, if available, pre-MTX liver histology gave an estimate of the probability of developing cirrhosis or fibrosis during treatment of psoriasis with weekly, oral doses of MTX. Methotrexate-induced cirrhosis requiring liver transplantation in three patients with psoriasis. A word of caution in light of the expanding use of this 'steroid-sparing' agent. Gilbert SC, Klintmalm G, Menter A, Silverman A. Arch.Int.Med. 1990 150:733-4. Three cases of methotrexate-induced cirrhosis requiring orthotopic liver transplantation are presented to emphasize the importance of strict adherence to published criteria for patient selection, monitoring of cumulative drug dosages, and the performance of serial liver biopsies. Low-dose methotrexate treatment of rheumatoid arthritis. Longterm observations. Weinstein A, Marlowe S, Korn J, Farouhar F. Am J Med. 1985 Sep;79(3):331-7. Liver toxicity assessed in 21 RA patients and four others receiving long-term methotrexate therapy revealed Acute hepatitis in one and elevated transaminase levels in 12 (48 percent). Liver biopsy specimens in 17 patients after a mean of 1,950 mg of methotrexate (range: 915 to 3,125) revealed mild fibrosis in six and no cirrhosis. Hepatic fibrosis and cirrhosis due to methotrexate may be less common in rheumatoid arthritis than has been reported in psoriasis. RA vs PSA on TNF Blockade: The CORRONA Database Prospective cohort of 5596 (2722 pt-years) RA; 524 (399 pt-years) PSA PSA have more liver AEs than RA Liver disease in PSA correlated with weight, male sex, past/present DMARD use and h/o liver disease Cassell et.al., Arthr.Rheum. 52(suppl.), abstract 491, 2005 Infliximab Liver toxicity in psoriasis patients in phase III trials No significant liver toxicity in rheumatoid arthritis patients in phase III trials