Abstract
Objective
The purpose of this open pilot study was to assess prospectively the effect of infliximab on extraintestinal manifestations in patients with active Crohn’s disease refractory to conventional treatment.
Patients and methods
Twenty-two consecutive patients with Crohn’s disease and one with ulcerative colitis presenting at least one of the known extraintestinal manifestations of Crohn’s disease participated in the study. All the patients had Crohn’s disease activity index (CAI) scores above 2. Each patient received an intravenous infusion of infliximab at a dosage of 5 mg/kg. A thorough questionnaire was used reviewing the extraintestinal manifestations of Crohn’s disease such as erythema nodosum, pyoderma gangrenosum, eye lesions, arthritis or arthralgia, sacroiliitis or inflammatory back pain, hepatic disease, hematologic manifestations (megaloblastic, iron deficiency or hemolytic anemia, thrombocytosis), thrombosis, and nephrolithiasis. Musculoskeletal complaints were evaluated using the parameters intensity of pain, duration of morning stiffness (in minutes), presence of inflammatory back pain, Schober’s test of the lumbar region, chest expansion, and distance from occiput to wall. The clinical assessment was performed on the day of the infusion and 2 weeks later.
Results
Eleven out of 23 patients had arthralgia of inflammatory nature, three others had evidence of active synovitis on physical examination, and 11 reported inflammatory back pain. Four patients suffered from protracted pyoderma gangrenosum; three had resistant aphthous stomatitis. Eleven patients had more than one extraintestinal manifestation. All four with pyoderma gangrenosum demonstrated significant improvement of their ulcers after one course of infliximab, with complete resolution of the skin lesions in three of them after repeated infusions of infliximab. Aphthous stomatitis completely responded in all patients after a single infusion. Seven out of 11 patients with arthralgia and seven out of 11 with inflammatory back pain/sacroiliitis experienced benefit after treatment with infliximab and reported at least partial clinical improvement in duration of morning stiffness, tender joint count, and visual analogue scale for pain. Only one of three patients with frank arthritis demonstrated clear improvement, and two others failed to respond to infliximab treatment.
Conclusion
These preliminary results are encouraging and suggest a promising role of infliximab in the treatment of extraintestinal symptoms of Crohn’s disease.
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References
Bernstein CN, Blanchard JF, Rawsthorne P et al (2001) The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol 96:1116–1122
Wollbeim FA (2001) Enteropathic arthritis. In: Ruddy S, Harris ED, Sledge CB (eds) Kelley’s textbook of rheumatology, 6th edn. Saunders, Philadelphia, pp 1081–1088
Salvarani C, Viachonikolis IG, van der Heijde DM et al (2001) Musculoskeletal manifestations in a population-based cohort of inflammatory bowel disease patients. Scand J Gastroenterol 36:1307–1313
Palm O, Moum B, Jahnsen J, Gran JT (2001) The prevalence and incidence of peripheral arthritis in patients with inflammatory bowel disease, a prospective population based study (the IBSEN study). Rheumatology 40:1256–1261
Veloso FT, Carvalho J, Magro F (1996) Immune-related systemic manifestations of inflammatory bowel disease. A prospective study of 792 patients. J Clin Gastroenterol 23:29–34
Badelon I (1999) Eye and spondyloarthropathies. Rev Prat 49:1995–1998
Udvardy M, Altorjay I, Palatka K (2001) Hematologic aspects of inflammatory bowel disease. Orv Hetil 142:883–886
Ricart E, Panaccione R, Loftus EV et al (2001) Infliximab for Crohn’s disease in clinical practice at the Mayo Clinic: the first 100 patients. Am J Gastroenterol 96:722–729
D’haens G, Van Deventer S, Van Hogezand R et al (1999) Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn’s disease: A European multicenter trial. Gastroenterology 116: 1029–1035
Targan SR, Hanauer SB, Van Deventer SJ et al (1997) A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s disease cA2 study group. N Engl J Med 337:10235
Present DH, Rutgeerts P, Targan S et al (1999) Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 340:1398–1405
Ellman MH, Hanauer S, Sitrin M et al (2001) Crohn’s disease arthritis treated with infliximab: an open trial in four patients. J Clin Rheumatol 7:67–71
Tan MH, Gordon M, Lebwohl O et al (2001) Improvement of pyoderma gangrenosum and psoriasis associated with Crohn’s disease with anti-tumor necrosis factor a monoclonal antibody. Arch Dermatol 37:930–933
Hughes AP, Jackson JM, Callen JP (2000) Clinical features and treatment of peristomal pyoderma gangrenosum. JAMA 284:1546–1548
Yoshida EM (1999) The Crohn’s disease activity index, its derivatives and the inflammatory bowel disease questionnaire: a review of instruments to assess Crohn’s disease. Can J Gastroenterol 13:65–73
Harvey RF, Bradshaw JM (1980) Measuring Crohn’s disease activity. Lancet 1:1134–1135
Van Deventer SJ (1999) Targeting TNF alpha as a key cytokine in the inflammatory processes of Crohn’s disease—the mechanisms of action of infliximab. Aliment Pharmacol Ther [Suppl 4]:3–8
Toussirot E, Wendling D (2001) Therapeutic advances in ankylosing spondylitis. Expert Opin Invest Drugs 10:21–29
Baeten D, Kruithof E, Van den Bosch F et al (2001) Immunomodulatory effects of anti-tumor necrosis factor a therapy on synovium in spondyloarthropathy. Histologic findings in eight patients from an open-label pilot study. Arthritis Rheum 44:186–195
Brandt J, Haibel H, Reddig J et al (2002) Successful short-term treatment of severe undifferentiated spondyloarthropathy with the anti-tumor necrosis factor-alpha monoclonal antibody infliximab. J Rheumatol 29:118–122
Keyser FD, Mielants H, Veys EM (2001) Current use of biological for the treatment of spondyloarthropathies. Expert Opin Pharmacother 2:85–93
Taylor PC, Williams RO, Maini RN (2001) Immunotherapy for rheumatoid arthritis. Curr Opin Immunol 13:611–616
Brandt J, Haibel H, Cornely D et al (2000) Successful treatment of active ankylosing spondylitis with the anti-tumor necrosis factor alpha monoclonal antibody infliximab. Arthritis Rheum 43:1346–1352
Van den Bosch F, Kruithof E, Baeten D et al (2000) Effects of a loading dose regimen of three infusions of chimeric monoclonal antibody to tumor necrosis factor alpha (infliximab) in spondyloarthropathy: an open pilot study. Ann Rheum Dis 59:428–433
Stone M, Salonen D, Lax M et al (2001) Clinical and imaging correlates of response to treatment with infliximab in patients with ankylosing spondylitis. J Rheumatol 28:1605–1614
Hadi A, Hickling P, Brown M, Al-Nahhas A (2002) Scintigraphic evidence of effect of infliximab on disease activity in ankylosing spondylitis. Rheumatology (Oxford) 41:114–116
Braun J, Brandt J, Listing J et al (2002) Treatment of active ankylosing spondylitis with infliximab: a randomized controlled multicentre trial. Lancet 359:1187–1193
Maksymowych WP, Jhangri GS, Lambert RG et al (2002) Infliximab in ankylosing spondylitis: a prospective observational inception cohort analysis of efficacy and safety. J Rheumatol 29:959–965
Gorman JD, Sack KE, Davis JC (2002) Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor. N Engl J Med 346:1349–1356
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Kaufman, I., Caspi, D., Yeshurun, D. et al. The effect of infliximab on extraintestinal manifestations of Crohn’s disease. Rheumatol Int 25, 406–410 (2005). https://doi.org/10.1007/s00296-004-0467-8
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DOI: https://doi.org/10.1007/s00296-004-0467-8