Gastrointestinal Perforations with Biologics in Patients with Rheumatoid Arthritis: Implications for Clinicians (2024)

1. Young A, Koduri G. Extra-articular manifestations and complications of rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2007;21(5):907–27.
   https://doi.org/10.1016/j.berh.2007.05.007
2. Wallis D. Infection risk and biologics: current update. Curr Opin Rheumatol. 2014;26(4):404–9.
   https://doi.org/10.1097/BOR.0000000000000072
3. Jacobs DO. Clinical practice. Diverticulitis. N Engl J Med. 2007;357(20):2057–66.
   https://doi.org/10.1056/NEJMcp073228
4. Vermeulen J, van der Harst E, Lange JF. Pathophysiology and prevention of diverticulitis and perforation. Neth J Med. 2010;68(10):303–9.
5. Tridente A, Clarke GM, Walden A, McKechnie S, Hutton P, Mills GH, et al. Patients with faecal peritonitis admitted to European intensive care units: an epidemiological survey of the GenOSept cohort. Intensive Care Med. 2014;40(2):202–10.
   https://doi.org/10.1007/s00134-013-3158-7
6. Morris AM, Regenbogen SE, Hardiman KM, Hendren S. Sigmoid diverticulitis: a systematic review. JAMA. 2014;311(3):287–97.
   https://doi.org/10.1001/jama.2013.282025
7. Horton KM, Corl FM, Fishman EK. CT evaluation of the colon: inflammatory disease. Radiographics. 2000;20(2):399–418.
   https://doi.org/10.1148/radiographics.20.2.g00mc15399
8. Biondo S, Trenti L, Elvira J, Golda T, Kreisler E. Outcomes of colonic diverticulitis according to the reason of immunosuppression. Am J Surg. 2016;212(3):384–90.
   https://doi.org/10.1016/j.amjsurg.2016.01.038
9. Pessaux P, Muscari F, Ouellet JF, Msika S, Hay JM, Millat B, et al. Risk factors for mortality and morbidity after elective sigmoid resection for diverticulitis: prospective multicenter multivariate analysis of 582 patients. World J Surg. 2004;28(1):92–6.
   https://doi.org/10.1007/s00268-003-7146-x
10. Curtis JR, Lanas A, John A, Johnson DA, Schulman KL. Factors associated with gastrointestinal perforation in a cohort of patients with rheumatoid arthritis. Arthritis Care Res. 2012;64(12):1819–28.
    https://doi.org/10.1002/acr.21764
11. Hernández-Díaz S, Rodríguez LA. Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s. Arch Intern Med. 2000;160(14):2093–9.
    https://doi.org/10.1001/archinte.160.14.2093
12. Larkai EN, Smith JL, Lidsky MD, Graham DY. Gastroduodenal mucosa and dyspeptic symptoms in arthritic patients during chronic nonsteroidal anti-inflammatory drug use. Am J Gastroenterol. 1987;82(11):1153–8.
13. Bardou M, Barkun AN. Preventing the gastrointestinal adverse effects of nonsteroidal anti-inflammatory drugs: from risk factor identification to risk factor intervention. Jt Bone Spine. 2010;77(1):6–12.
    https://doi.org/10.1016/j.jbspin.2009.11.008
14. Goldstein JL, Eisen GM, Lewis B, Gralnek IM, Zlotnick S, Fort JG, et al. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clin Gastroenterol Hepatol. 2005;3(2):133–41.
    https://doi.org/10.1016/S1542-3565(04)00619-6
15. Humes DJ, Fleming KM, Spiller RC, West J. Concurrent drug use and the risk of perforated colonic diverticular disease: a population-based case-control study. Gut. 2011;60(2):219–24.
    https://doi.org/10.1136/gut.2010.217281
16. Lanas A, Perez-Aisa MA, Feu F, Ponce J, Saperas E, Santolaria S, et al. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use. Am J Gastroenterol. 2005;100(8):1685–93.
    https://doi.org/10.1111/j.1572-0241.2005.41833.x
17. Wallace JL. Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn’t the stomach digest itself? Physiol Rev. 2008;88(4):1547–65.
    https://doi.org/10.1152/physrev.00004.2008
18. Rostom A, Muir K, Dubé C, Jolicoeur E, Boucher M, Joyce J, et al. Gastrointestinal safety of cyclooxygenase-2 inhibitors: a Cochrane Collaboration systematic review. Clin Gastroenterol Hepatol. 2007;5(7):818–28, 28.e1–5 (quiz 768).
    https://doi.org/10.1016/j.cgh.2007.03.011
19. Wallace JL, McKnight W, Reuter BK, Vergnolle N. NSAID-induced gastric damage in rats: requirement for inhibition of both cyclooxygenase 1 and 2. Gastroenterology. 2000;119(3):706–14.
    https://doi.org/10.1053/gast.2000.16510
20. Matsui H, Shimokawa O, Kaneko T, Nagano Y, Rai K, Hyodo I. The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine. J Clin Biochem Nutr. 2011;48(2):107–11.
    https://doi.org/10.3164/jcbn.10-79
21. Kefalakes H, Stylianides TJ, Amanakis G, Kolios G. Exacerbation of inflammatory bowel diseases associated with the use of nonsteroidal anti-inflammatory drugs: myth or reality? Eur J Clin Pharmacol. 2009;65(10):963–70.
    https://doi.org/10.1007/s00228-009-0719-3
22. Curtis JR, Xie F, Chen L, Spettell C, McMahan RM, Fernandes J, et al. The incidence of gastrointestinal perforations among rheumatoid arthritis patients. Arthritis Rheum. 2011;63(2):346–51.
    https://doi.org/10.1002/art.30107
23. Saag KG, Koehnke R, Caldwell JR, Brasington R, Burmeister LF, Zimmerman B, et al. Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med. 1994;96(2):115–23.
    https://doi.org/10.1016/0002-9343(94)90131-7
24. Mpofu S, Mpofu CM, Hutchinson D, Maier AE, Dodd SR, Moots RJ. Steroids, non-steroidal anti-inflammatory drugs, and sigmoid diverticular abscess perforation in rheumatic conditions. Ann Rheum Dis. 2004;63(5):588–90.
    https://doi.org/10.1136/ard.2003.010355
25. Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open. 2014;4(5):e004587.
    https://doi.org/10.1136/bmjopen-2013-004587
26. Schäcke H, Döcke WD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. 2002;96(1):23–43.
    https://doi.org/10.1016/S0163-7258(02)00297-8
27. Genta MS, Genta RM, Gabay C. Systemic rheumatoid vasculitis: a review. Semin Arthritis Rheum. 2006;36(2):88–98.
    https://doi.org/10.1016/j.semarthrit.2006.04.006
28. Babian M, Nasef S, Soloway G. Gastrointestinal infarction as a manifestation of rheumatoid vasculitis. Am J Gastroenterol. 1998;93(1):119–20.
    https://doi.org/10.1111/j.1572-0241.1998.119_c.x
29. Bienenstock H, Minick CR, Rogoff B. Mesenteric arteritis and intestinal infarction in rheumatoid disease. Arch Intern Med. 1967;119(4):359–64.
    https://doi.org/10.1001/archinte.1967.00290220109006
30. Corsi F, Previde P, Colombo F, Cellerino P, Donati M, Trabucchi E. Two cases of intestinal perforation in patients on anti-rheumatic treatment with etanercept. Clin Exp Rheumatol. 2006;24(1):113.
31. Curtis JR, Chen SY, Werther W, John A, Johnson DA. Validation of ICD-9-CM codes to identify gastrointestinal perforation events in administrative claims data among hospitalized rheumatoid arthritis patients. Pharmacoepidemiol Drug Saf. 2011;20(11):1150–8.
    https://doi.org/10.1002/pds.2215
32. Monemi S, Berber E, Sarsour K, Wang J, Lampl K, Bharucha K, et al. Incidence of gastrointestinal perforations in patients with rheumatoid arthritis treated with tocilizumab from clinical trial, postmarketing, and real-world data sources. Rheumatol Ther. 2016;3(2):337–52.
    https://doi.org/10.1007/s40744-016-0037-z
33. Xie F, Yun H, Bernatsky S, Curtis JR. Brief report: risk of gastrointestinal perforation among rheumatoid arthritis patients receiving tofacitinib, tocilizumab, or other biologic treatments. Arthritis Rheumatol. 2016;68(11):2612–7.
    https://doi.org/10.1002/art.39761
34. Curtis JR, Perez-Gutthann S, Suissa S, Napalkov P, Singh N, Thompson L, et al. Tocilizumab in rheumatoid arthritis: a case study of safety evaluations of a large postmarketing data set from multiple data sources. Semin Arthritis Rheum. 2015;44(4):381–8.
    https://doi.org/10.1016/j.semarthrit.2014.07.006
35. Závada J, Lunt M, Davies R, Low AS, Mercer LK, Galloway JB, et al. The risk of gastrointestinal perforations in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the BSRBR-RA. Ann Rheum Dis. 2014;73(1):252–5.
    https://doi.org/10.1136/annrheumdis-2012-203102
36. Fleischmann R, Rubbert-Roth A, Combe B, et al. FRI0173 Gastrointestinal perforations with certolizumab PEGOL. Ann Rheum Dis. 2013;71:370.
37. Navarro-Millán I, Singh JA, Curtis JR. Systematic review of tocilizumab for rheumatoid arthritis: a new biologic agent targeting the interleukin-6 receptor. Clin Ther. 2012;34(4):788–802.e3.
    https://doi.org/10.1016/j.clinthera.2012.02.014
38. Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Aleco*ck E, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008;371(9617):987–97.
    https://doi.org/10.1016/S0140-6736(08)60453-5
39. Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008;67(11):1516–23.
    https://doi.org/10.1136/ard.2008.092932
40. Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2010;69(1):88–96.
    https://doi.org/10.1136/ard.2008.105197
41. Gout T, Ostor AJ, Nisar MK. Lower gastrointestinal perforation in rheumatoid arthritis patients treated with conventional DMARDs or tocilizumab: a systematic literature review. Clin Rheumatol. 2011;30(11):1471–4.
    https://doi.org/10.1007/s10067-011-1827-x
42. Genovese MC, Rubbert-Roth A, Smolen JS, Kremer J, Khraishi M, Gómez-Reino J, et al. Longterm safety and efficacy of tocilizumab in patients with rheumatoid arthritis: a cumulative analysis of up to 4.6 years of exposure. J Rheumatol. 2013;40(6):768–80.
    https://doi.org/10.3899/jrheum.120687
43. Lazzerini PE, Capecchi PL, Guidelli GM, Selvi E, Acampa M, Laghi-Pasini F. Spotlight on sirukumab for the treatment of rheumatoid arthritis: the evidence to date. Drug Des Devel Ther. 2016;10:3083–98.
    https://doi.org/10.2147/DDDT.S99898
44. Aletaha D, Bingham CO, Tanaka Y, Agarwal P, Kurrasch R, Tak PP, et al. Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy (SIRROUND-T): a randomised, double-blind, placebo-controlled, parallel-group, multinational, phase 3 study. Lancet. 2017;389(10075):1206–17.
    https://doi.org/10.1016/S0140-6736(17)30401-4
45. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–42.
    https://doi.org/10.1056/NEJMoa032691
46. Verheul HM, Lolkema MP, Qian DZ, Hilkes YH, Liapi E, Akkerman JW, et al. Platelets take up the monoclonal antibody bevacizumab. Clin Cancer Res. 2007;13(18 Pt 1):5341–7.
    https://doi.org/10.1158/1078-0432.CCR-07-0847
47. Verheul HM, Pinedo HM. Possible molecular mechanisms involved in the toxicity of angiogenesis inhibition. Nat Rev Cancer. 2007;7(6):475–85.
    https://doi.org/10.1038/nrc2152
48. Schmidinger M. Understanding and managing toxicities of vascular endothelial growth factor (VEGF) inhibitors. EJC Suppl. 2013;11(2):172–91.
    https://doi.org/10.1016/j.ejcsup.2013.07.016
49. Gyires K. Gastric mucosal protection: from prostaglandins to gene-therapy. Curr Med Chem. 2005;12(2):203–15.
    https://doi.org/10.2174/0929867053363478
50. Nakahara H, Song J, Sugimoto M, Hagihara K, Kishimoto T, Yoshizaki K, et al. Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis. Arthritis Rheum. 2003;48(6):1521–9.
    https://doi.org/10.1002/art.11143
51. Kuhn KA, Manieri NA, Liu TC, Stappenbeck TS. IL-6 stimulates intestinal epithelial proliferation and repair after injury. PLoS One. 2014;9(12):e114195.
    https://doi.org/10.1371/journal.pone.0114195
52. Strangfeld A, Richter A, Siegmund B, Herzer P, Rockwitz K, Demary W, et al. Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs. Ann Rheum Dis. 2017;76(3):504–10.
    https://doi.org/10.1136/annrheumdis-2016-209773
53. Migita K, Izumi Y, Jiuchi Y, Kozuru H, Kawahara C, Izumi M, et al. Effects of Janus kinase inhibitor tofacitinib on circulating serum amyloid A and interleukin-6 during treatment for rheumatoid arthritis. Clin Exp Immunol. 2014;175(2):208–14.
    https://doi.org/10.1111/cei.12234
54. Geirsson AJ, Sturfelt G, Truedsson L. Clinical and serological features of severe vasculitis in rheumatoid arthritis: prognostic implications. Ann Rheum Dis. 1987;46(10):727–33.
    https://doi.org/10.1136/ard.46.10.727
55. Hart AR, Kennedy HJ, Stebbings WS, Day NE. How frequently do large bowel diverticula perforate? An incidence and cross-sectional study. Eur J Gastroenterol Hepatol. 2000;12(6):661–5.
    https://doi.org/10.1097/00042737-200012060-00016
56. Chapman J, Davies M, Wolff B, Dozois E, Tessier D, Harrington J, et al. Complicated diverticulitis: is it time to rethink the rules? Ann Surg. 2005;242(4):576–81 (discussion 81–83).
    https://doi.org/10.1097/01.sla.0000184843.89836.35

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