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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