- Email: [email protected]
Cost-effectiveness of colorectal cancer screening strategies
2026 CORRESPONDENCE
GASTROENTEROLOGY Vol. 110, No. 6
4. Tu JB, Blackwell RQ. Studies on levels of penicillamine-induced cupriuresis in heterozygotes of Wilson’s disease. Metabolism 1967;16:507–513. 5. Thomas GR, Bull PC, Roberts EA, Walshe JM, Cox DW. Haplotype studies in Wilson’s disease. Am J Hum Genet 1994;54:71–78. 6. Thomas GR, Forbes JR, Roberts EA, Walshe JM, Cox DW. The Wilson disease gene: spectrum of mutations and their consequences. Nat Genet 1995;9:210–217. 7. Polli C, Maier-Dobersberger T, Morris P, Cauza E, Yeganehfar C, Ferenci P. A nested PCR based assay for the HIS1070GLN mutation in Wilson’s disease for family screening (abstr). Gastroenterology 1996; 110:A1297.
Cost-effectiveness of Colorectal Cancer Screening Strategies Dear Sir: Leiberman’s cost-effectiveness model1 simulating alternative colorectal cancer screening strategies underscores the importance of patient compliance in achieving the benefits of all available prevention programs. As resources for health care services have become more limited, economic assessment of medical interventions has become increasingly important to providers and health plan managers. Concurrently, the methods of cost-effectiveness analyses have become more standardized.2 We would like to address several shortcomings in the methodology and assumptions of Leiberman’s model. The performance characteristics of the screening procedures used in the model are inconsistent. The model presupposes that the sensitivity of fecal occult blood testing for detecting colorectal cancer is identical to the sensitivity of combined flexible sigmoidoscopy and fecal occult blood testing. This implies that all tumors within reach of the sigmoidoscope are detected by fecal occult blood testing. In fact, several studies have shown that fecal occult blood testing has limitations in detecting cancers both proximal and distal to the splenic flexure.3,4 The failure to include an improved detection rate due to sigmoidoscopy is a bias against the strategy that combines sigmoidoscopy and fecal occult blood testing. The use of fee for service charges rather than actual payments received does not represent the true cost to third-party payers. Although this limitation can be addressed through the use of formal sensitivity analysis, Dr. Leiberman’s model only performs this analysis for colonoscopy. Because flexible sigmoidoscopy is perhaps the most widely recommended screening procedure, a similar analysis varying the cost of sigmoidoscopy is warranted. Even in a period covering 10 years, the concept of discounting costs and lives saved must be considered. Because any benefit gained in the present is more valuable than the same benefit 10 years from now, discounting is critical when comparing strategies with costs that differ as a function of time. Omission of discounting is a bias in favor of screening strategies that use a larger percentage of resources initially, such as the one-time colonoscopy strategy. Finally, although the outcomes measured show the efficacy and cost-effectiveness of alternative screening strategies, the model fails to produce a measure of cost-effectiveness that allows health care providers to choose the strategy of greatest value as measured in cost per life year gained. This standard would provide a measure that could be compared with other clinical interventions. We agree with Leiberman that an age-adjusted model5 estimating the incremental costs per additional life year gained is needed before physicians, patients, and health insurers can support one colorectal cancer screening strategy.
/ 5E0E$$0065
05-07-96 00:34:11
gasa
WILLIAM M. TIERNEY, M.D.
Division of Gastroenterology A. MARK FENDRICK, M.D.
Division of General Medicine University of Michigan Medical Center Ann Arbor, Michigan 1. Lieberman D. Cost-effectiveness model for colon cancer screening. Gastroenterology 1995;109:1781–1790. 2. Eisenberg JM. Clinical economics: a guide to the economic analysis of clinical practices. JAMA 1989;262:2879–2886. 3. Ahlquist DA, Wieand HS, Moertel CG, McGill DB, Loprinzi CL, O’Connell MJ, Mailliard JA, Gerstner JB, Pandya K, Ellefson RD. Accuracy of fecal occult blood screening for colorectal neoplasia. JAMA 1993;269:1262–1267. 4. Allison JE, Tekawa IS, Ransom LJ, Adrian AL. A comparison of fecal occult blood tests for colorectal cancer screening. N Engl J Med 1996;334:155–159. 5. Wagner JL, Herdman RC, Wadhwa S. Cost effectiveness of colorectal cancer screening in the elderly. Ann Intern Med 1991;115: 807–817.
Reply. The colon cost-effectiveness model1 was intended to provide a relatively simplified method for comparing different colorectal cancer screening programs and determining which variables impact costeffectiveness. Previous work2 has already suggested that any of the proposed programs could be ‘‘cost-effective’’ relative to other disease management programs. My hope was that health care providers could ‘‘plug in’’ their own numbers to determine what might be most effective in their patient population or setting. The model uses some baseline assumptions regarding cost, but any figure (including true cost) could be tested in the model. The range of costs used in the sensitivity analysis illustrates the effect of changing cost assumptions on each program. Tierney and Fendrick were critical of a specific assumption used in the analysis of the combined flexible sigmoidoscopy plus fecal occult blood test strategy (FS/FOBT). They note that the rates of cancer detection used for both fecal occult blood test (FOBT) alone and FS/FOBT are 80%. They argue that this assumption could result in a bias against the FS/FOBT strategy. The actual cancer detection rate for combined screening is unknown but can be roughly calculated from existing data as follows. Flexible sigmoidoscopy is 70%–80% effective in reducing mortality from left-sided colorectal cancer and about 20% effective in reducing mortality from right-sided cancers.3,4 Annual FOBT could reduce proximal cancer mortality by an additional 33%.5 Therefore, overall mortality reduction from combined screening should be 66%. The assumptions used for the FS/FOBT strategy (80% cancer detection rate; 67% polyp detection rate) result in a 66% reduction in mortality when compliance is 100%. It should also be noted that the same approach was taken with the calculation of assumptions used in FOBT alone strategy. The mortality reduction of 35% (at 75% compliance) is roughly equal to the mortality reduction in a study by Mandel et al.5 Tierney and Fendrick point out that discounting costs and lives saved should have been incorporated into the model; I think this is valid critique. Because the model used a 10-year time period, I did not feel that discounting would have a major effect on the outcome and would make the model more difficult to apply. Nevertheless, I think that they make a good point that this approach could lead to some bias toward one-time colonoscopy, which expends most resources in the initial screening period. I wish to reemphasize that the primary reason for creating the model was to provide health care providers with a simple tool for
WBS-Gastro
June 1996
CORRESPONDENCE 2027
determining which variables will impact cost-effectiveness. Once there are real data, rather than assumptions, models such as that developed by the Office of Technology Assessment2 should be used to determine a more precise calculation of the cost of quality adjusted life years saved by screening. In the meantime, this model can highlight potential limitations of screening and lead to development of improved strategies in the future. Perhaps the most important variable is patient compliance, which has a significant impact on all of the screening strategies, a point reemphasized by Tierney and Fendrick. In my view, the model emphasizes the need to redouble our efforts to improve patient compliance through educational programs directed at both physicians and patients. DAVID LIEBERMAN, M.D.
Division of Gastroenterology Oregon Health Sciences University and Gastroenterology Section Portland VA Medical Center Portland, Oregon 97207 1. Lieberman DA. Cost-effectiveness model for colon cancer screening. Gastroenterology 1995;109:1781–1790. 2. Wagner JL, Herdman RC, Wadhwa S. Cost-effectiveness of colorectal cancer screening in the elderly. Ann Intern Med 1991;115: 807–817. 3. Selby JV, Friedman GD, Quesenberry CP Jr, Weiss NS. A casecontrol study of screening sigmoidscopy and mortality from colorectal cancer. N Engl J Med 1992;326:653–657. 4. Newcomb PA, Norfleet RG, Storer BE, Surawicz TS, Marcus PM. Screening sigmoidoscopy and colorectal cancer mortality. J Natl Cancer Inst 1992;84:1572–1575. 5. Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, Ederer F. Reducing mortality from colorectal cancer by screening for fecal occult blood. N Engl J Med 1993;328:1365–1371.
Azathioprine and 6-Mercaptopurine and Autoimmune Hepatitis Dear Sir: Pratt et al. are to be commended for their insightful report regarding the use of azathioprine (AZA) and 6-mercaptopurine (6-MP) in the treatment of autoimmune hepatitis.1 One of the case records included (patient 1) describes a documented biochemical and histological response to treatment with a combination of glucocorticoids and 6-MP after the patient did not achieve remission while undergoing therapy using a combination of glucocorticoids and AZA. Glucocorticoid therapy was subsequently withdrawn, and the patient was successfully maintained on 6-MP alone. In their discussion, the authors suggest that AZA may not always be a superior immunosuppressant and, in this isolated situation, 6-MP was more effective. Our concern regarding this conclusion relates to the authors’ use of ‘‘similar’’ doses of the two immunosuppressants on a milligram per kilogram basis. Because AZA is a prodrug and the two immunosuppressants have both different bioavailabilities and molecular weights, one cannot assume that equivalent oral doses on a milligram per kilogram basis will yield comparable immunosuppressive effects.2 – 4 Specifically, when comparing oral dosing of AZA and 6-MP, a conversion factor of 0.48 [(0.48)(AZA) Å 6-MP] has been used to account for the metabolism of AZA to 6-MP and a molecular weight ratio of 0.55.5 Given the above considerations, in addition to the other possible explanations outlined by the investigators, one must also consider that patient 1 may have ultimately responded to AZA had an ‘‘equivalent
/ 5E0E$$0065
05-07-96 00:34:11
gasa
immunosuppressive dose’’ been used (i.e., 75 mg 6-MP/0.48 Å 156 mg AZA). The patient’s superior response to 6-MP may simply have reflected the higher ‘‘immunosuppressive dose’’ that was used. JOSEPH C. YARZE, M.D., F.A.C.P. KEVIN J. HERLIHY, M.D. HOWARD P. FRITZ, M.D. ANNA M. POULOS, M.D.
Gastroenterology Associates of Northern New York 3 Irongate Center P. O. Box 2368 Glens Falls, New York 12801 1. Pratt DS, Flavin DP, Kaplan MM. The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine. Gastroenterology 1996;110:271–274. 2. Zimm S, Collins JN, Riccardi R, O’Neil D, Narang PK, Chabner B, Poplack DG. Variable bioavailability of oral mercaptopurine. Is maintenance chemotherapy in acute lymphoblastic leukemia being optimally delivered? N Engl J Med 1983;308:1005–1009. 3. Van Os EC, Zins BJ, Sandborn WJ, Mays DC, Schriver ZE, Tremaine WJ, Mahoney DW, Zinsmeister AR, Lipsky JJ. Azathioprine pharmacokinetics following single dose IV, oral, delayed-release oral and rectal foam administration (abstr). Gastroenterology 1995;108: A934. 4. Odlind B, Hartvig P, Lindstrom B, Lonnerholm G, Tufveson G, Gresberg N. Serum azathioprine and 6-mercaptopurine levels and immunosuppressive activity after azathioprine in uremic patients. Int J Immunopharmacol 1986;8:1–11. 5. Sandborn WJ, Van Os EC, Zins BJ, Tremaine WJ, Mays DC, Lipsky JJ. An intravenous loading dose of azathioprine decreases the time to response in patients with Crohn’s disease. Gastroenterology 1995;109:1808–1817.
Reply. We thank Dr. Yarze and colleagues for their interest in our recent report.1 While the conversion value mentioned by them is useful for comparing the intravenous dosing of AZA and 6-MP,2 we do not believe that there are data supporting its validity for an oral route of administration. Both agents have low and variable bioavailabilities when given orally, and at least one study has shown that AZA is better absorbed from the gastrointestinal tract.3 Therefore, although there may well have been some degree of difference in the ‘‘immunosuppressive’’ dosing of the AZA and 6-MP in patient 1, we do not believe that the 75 mg (1.5 mg/kg) of 6-MP given to the patient is equal to 156 mg (3.125 mg/kg) of AZA. In addition, we were compelled to stop AZA administration because of a significant worsening of the aminotransferase levels despite a stable dose of glucocorticoids during therapy. DANIEL S. PRATT, M.D. MARSHALL M. KAPLAN, M.D.
Division of Gastroenterology New England Medical Center Tufts University School of Medicine Boston, Massachusetts 02111 1. Pratt DS, Flavin DP, Kaplan MM. The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine. Gastroenterology 1996;110:271–274. 2. Sandborn WJ, VanOs EC, Zins BJ, Tremaine WJ, Mays DC, Lipsky JJ. An intravenous loading dose of azathioprine decreases the time to response in patients with Crohn’s disease. Gastroenterology 1995;109:1808–1817. 3. Elion GB. The pharmacology of azathioprine. Ann NY Acad Sci 1993;685:400–407.
WBS-Gastro
GASTROENTEROLOGY Vol. 110, No. 6
4. Tu JB, Blackwell RQ. Studies on levels of penicillamine-induced cupriuresis in heterozygotes of Wilson’s disease. Metabolism 1967;16:507–513. 5. Thomas GR, Bull PC, Roberts EA, Walshe JM, Cox DW. Haplotype studies in Wilson’s disease. Am J Hum Genet 1994;54:71–78. 6. Thomas GR, Forbes JR, Roberts EA, Walshe JM, Cox DW. The Wilson disease gene: spectrum of mutations and their consequences. Nat Genet 1995;9:210–217. 7. Polli C, Maier-Dobersberger T, Morris P, Cauza E, Yeganehfar C, Ferenci P. A nested PCR based assay for the HIS1070GLN mutation in Wilson’s disease for family screening (abstr). Gastroenterology 1996; 110:A1297.
Cost-effectiveness of Colorectal Cancer Screening Strategies Dear Sir: Leiberman’s cost-effectiveness model1 simulating alternative colorectal cancer screening strategies underscores the importance of patient compliance in achieving the benefits of all available prevention programs. As resources for health care services have become more limited, economic assessment of medical interventions has become increasingly important to providers and health plan managers. Concurrently, the methods of cost-effectiveness analyses have become more standardized.2 We would like to address several shortcomings in the methodology and assumptions of Leiberman’s model. The performance characteristics of the screening procedures used in the model are inconsistent. The model presupposes that the sensitivity of fecal occult blood testing for detecting colorectal cancer is identical to the sensitivity of combined flexible sigmoidoscopy and fecal occult blood testing. This implies that all tumors within reach of the sigmoidoscope are detected by fecal occult blood testing. In fact, several studies have shown that fecal occult blood testing has limitations in detecting cancers both proximal and distal to the splenic flexure.3,4 The failure to include an improved detection rate due to sigmoidoscopy is a bias against the strategy that combines sigmoidoscopy and fecal occult blood testing. The use of fee for service charges rather than actual payments received does not represent the true cost to third-party payers. Although this limitation can be addressed through the use of formal sensitivity analysis, Dr. Leiberman’s model only performs this analysis for colonoscopy. Because flexible sigmoidoscopy is perhaps the most widely recommended screening procedure, a similar analysis varying the cost of sigmoidoscopy is warranted. Even in a period covering 10 years, the concept of discounting costs and lives saved must be considered. Because any benefit gained in the present is more valuable than the same benefit 10 years from now, discounting is critical when comparing strategies with costs that differ as a function of time. Omission of discounting is a bias in favor of screening strategies that use a larger percentage of resources initially, such as the one-time colonoscopy strategy. Finally, although the outcomes measured show the efficacy and cost-effectiveness of alternative screening strategies, the model fails to produce a measure of cost-effectiveness that allows health care providers to choose the strategy of greatest value as measured in cost per life year gained. This standard would provide a measure that could be compared with other clinical interventions. We agree with Leiberman that an age-adjusted model5 estimating the incremental costs per additional life year gained is needed before physicians, patients, and health insurers can support one colorectal cancer screening strategy.
/ 5E0E$$0065
05-07-96 00:34:11
gasa
WILLIAM M. TIERNEY, M.D.
Division of Gastroenterology A. MARK FENDRICK, M.D.
Division of General Medicine University of Michigan Medical Center Ann Arbor, Michigan 1. Lieberman D. Cost-effectiveness model for colon cancer screening. Gastroenterology 1995;109:1781–1790. 2. Eisenberg JM. Clinical economics: a guide to the economic analysis of clinical practices. JAMA 1989;262:2879–2886. 3. Ahlquist DA, Wieand HS, Moertel CG, McGill DB, Loprinzi CL, O’Connell MJ, Mailliard JA, Gerstner JB, Pandya K, Ellefson RD. Accuracy of fecal occult blood screening for colorectal neoplasia. JAMA 1993;269:1262–1267. 4. Allison JE, Tekawa IS, Ransom LJ, Adrian AL. A comparison of fecal occult blood tests for colorectal cancer screening. N Engl J Med 1996;334:155–159. 5. Wagner JL, Herdman RC, Wadhwa S. Cost effectiveness of colorectal cancer screening in the elderly. Ann Intern Med 1991;115: 807–817.
Reply. The colon cost-effectiveness model1 was intended to provide a relatively simplified method for comparing different colorectal cancer screening programs and determining which variables impact costeffectiveness. Previous work2 has already suggested that any of the proposed programs could be ‘‘cost-effective’’ relative to other disease management programs. My hope was that health care providers could ‘‘plug in’’ their own numbers to determine what might be most effective in their patient population or setting. The model uses some baseline assumptions regarding cost, but any figure (including true cost) could be tested in the model. The range of costs used in the sensitivity analysis illustrates the effect of changing cost assumptions on each program. Tierney and Fendrick were critical of a specific assumption used in the analysis of the combined flexible sigmoidoscopy plus fecal occult blood test strategy (FS/FOBT). They note that the rates of cancer detection used for both fecal occult blood test (FOBT) alone and FS/FOBT are 80%. They argue that this assumption could result in a bias against the FS/FOBT strategy. The actual cancer detection rate for combined screening is unknown but can be roughly calculated from existing data as follows. Flexible sigmoidoscopy is 70%–80% effective in reducing mortality from left-sided colorectal cancer and about 20% effective in reducing mortality from right-sided cancers.3,4 Annual FOBT could reduce proximal cancer mortality by an additional 33%.5 Therefore, overall mortality reduction from combined screening should be 66%. The assumptions used for the FS/FOBT strategy (80% cancer detection rate; 67% polyp detection rate) result in a 66% reduction in mortality when compliance is 100%. It should also be noted that the same approach was taken with the calculation of assumptions used in FOBT alone strategy. The mortality reduction of 35% (at 75% compliance) is roughly equal to the mortality reduction in a study by Mandel et al.5 Tierney and Fendrick point out that discounting costs and lives saved should have been incorporated into the model; I think this is valid critique. Because the model used a 10-year time period, I did not feel that discounting would have a major effect on the outcome and would make the model more difficult to apply. Nevertheless, I think that they make a good point that this approach could lead to some bias toward one-time colonoscopy, which expends most resources in the initial screening period. I wish to reemphasize that the primary reason for creating the model was to provide health care providers with a simple tool for
WBS-Gastro
June 1996
CORRESPONDENCE 2027
determining which variables will impact cost-effectiveness. Once there are real data, rather than assumptions, models such as that developed by the Office of Technology Assessment2 should be used to determine a more precise calculation of the cost of quality adjusted life years saved by screening. In the meantime, this model can highlight potential limitations of screening and lead to development of improved strategies in the future. Perhaps the most important variable is patient compliance, which has a significant impact on all of the screening strategies, a point reemphasized by Tierney and Fendrick. In my view, the model emphasizes the need to redouble our efforts to improve patient compliance through educational programs directed at both physicians and patients. DAVID LIEBERMAN, M.D.
Division of Gastroenterology Oregon Health Sciences University and Gastroenterology Section Portland VA Medical Center Portland, Oregon 97207 1. Lieberman DA. Cost-effectiveness model for colon cancer screening. Gastroenterology 1995;109:1781–1790. 2. Wagner JL, Herdman RC, Wadhwa S. Cost-effectiveness of colorectal cancer screening in the elderly. Ann Intern Med 1991;115: 807–817. 3. Selby JV, Friedman GD, Quesenberry CP Jr, Weiss NS. A casecontrol study of screening sigmoidscopy and mortality from colorectal cancer. N Engl J Med 1992;326:653–657. 4. Newcomb PA, Norfleet RG, Storer BE, Surawicz TS, Marcus PM. Screening sigmoidoscopy and colorectal cancer mortality. J Natl Cancer Inst 1992;84:1572–1575. 5. Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, Ederer F. Reducing mortality from colorectal cancer by screening for fecal occult blood. N Engl J Med 1993;328:1365–1371.
Azathioprine and 6-Mercaptopurine and Autoimmune Hepatitis Dear Sir: Pratt et al. are to be commended for their insightful report regarding the use of azathioprine (AZA) and 6-mercaptopurine (6-MP) in the treatment of autoimmune hepatitis.1 One of the case records included (patient 1) describes a documented biochemical and histological response to treatment with a combination of glucocorticoids and 6-MP after the patient did not achieve remission while undergoing therapy using a combination of glucocorticoids and AZA. Glucocorticoid therapy was subsequently withdrawn, and the patient was successfully maintained on 6-MP alone. In their discussion, the authors suggest that AZA may not always be a superior immunosuppressant and, in this isolated situation, 6-MP was more effective. Our concern regarding this conclusion relates to the authors’ use of ‘‘similar’’ doses of the two immunosuppressants on a milligram per kilogram basis. Because AZA is a prodrug and the two immunosuppressants have both different bioavailabilities and molecular weights, one cannot assume that equivalent oral doses on a milligram per kilogram basis will yield comparable immunosuppressive effects.2 – 4 Specifically, when comparing oral dosing of AZA and 6-MP, a conversion factor of 0.48 [(0.48)(AZA) Å 6-MP] has been used to account for the metabolism of AZA to 6-MP and a molecular weight ratio of 0.55.5 Given the above considerations, in addition to the other possible explanations outlined by the investigators, one must also consider that patient 1 may have ultimately responded to AZA had an ‘‘equivalent
/ 5E0E$$0065
05-07-96 00:34:11
gasa
immunosuppressive dose’’ been used (i.e., 75 mg 6-MP/0.48 Å 156 mg AZA). The patient’s superior response to 6-MP may simply have reflected the higher ‘‘immunosuppressive dose’’ that was used. JOSEPH C. YARZE, M.D., F.A.C.P. KEVIN J. HERLIHY, M.D. HOWARD P. FRITZ, M.D. ANNA M. POULOS, M.D.
Gastroenterology Associates of Northern New York 3 Irongate Center P. O. Box 2368 Glens Falls, New York 12801 1. Pratt DS, Flavin DP, Kaplan MM. The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine. Gastroenterology 1996;110:271–274. 2. Zimm S, Collins JN, Riccardi R, O’Neil D, Narang PK, Chabner B, Poplack DG. Variable bioavailability of oral mercaptopurine. Is maintenance chemotherapy in acute lymphoblastic leukemia being optimally delivered? N Engl J Med 1983;308:1005–1009. 3. Van Os EC, Zins BJ, Sandborn WJ, Mays DC, Schriver ZE, Tremaine WJ, Mahoney DW, Zinsmeister AR, Lipsky JJ. Azathioprine pharmacokinetics following single dose IV, oral, delayed-release oral and rectal foam administration (abstr). Gastroenterology 1995;108: A934. 4. Odlind B, Hartvig P, Lindstrom B, Lonnerholm G, Tufveson G, Gresberg N. Serum azathioprine and 6-mercaptopurine levels and immunosuppressive activity after azathioprine in uremic patients. Int J Immunopharmacol 1986;8:1–11. 5. Sandborn WJ, Van Os EC, Zins BJ, Tremaine WJ, Mays DC, Lipsky JJ. An intravenous loading dose of azathioprine decreases the time to response in patients with Crohn’s disease. Gastroenterology 1995;109:1808–1817.
Reply. We thank Dr. Yarze and colleagues for their interest in our recent report.1 While the conversion value mentioned by them is useful for comparing the intravenous dosing of AZA and 6-MP,2 we do not believe that there are data supporting its validity for an oral route of administration. Both agents have low and variable bioavailabilities when given orally, and at least one study has shown that AZA is better absorbed from the gastrointestinal tract.3 Therefore, although there may well have been some degree of difference in the ‘‘immunosuppressive’’ dosing of the AZA and 6-MP in patient 1, we do not believe that the 75 mg (1.5 mg/kg) of 6-MP given to the patient is equal to 156 mg (3.125 mg/kg) of AZA. In addition, we were compelled to stop AZA administration because of a significant worsening of the aminotransferase levels despite a stable dose of glucocorticoids during therapy. DANIEL S. PRATT, M.D. MARSHALL M. KAPLAN, M.D.
Division of Gastroenterology New England Medical Center Tufts University School of Medicine Boston, Massachusetts 02111 1. Pratt DS, Flavin DP, Kaplan MM. The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine. Gastroenterology 1996;110:271–274. 2. Sandborn WJ, VanOs EC, Zins BJ, Tremaine WJ, Mays DC, Lipsky JJ. An intravenous loading dose of azathioprine decreases the time to response in patients with Crohn’s disease. Gastroenterology 1995;109:1808–1817. 3. Elion GB. The pharmacology of azathioprine. Ann NY Acad Sci 1993;685:400–407.
WBS-Gastro