Lack of Increased Risk of Lymphoma by Thiopurines or Biologics in Japanese Patients with Inflammatory Bowel Disease: A Large-Scale Administrative Database Analysis

Abstract

Background and Aims Patients with inflammatory bowel diseases may have higher incidences of non-melanoma skin cancers and non-Hodgkin lymphoma, potentially linked to underlying disease and treatments. This analysis assessed incidence rates of these malignancies in Japanese patients with ulcerative colitis or Crohn’s disease, and their association with thiopurine and/or anti-tumor necrosis factor-α treatment, using data from a nationwide administrative database in Japan. Methods Patients diagnosed with inflammatory bowel disease without malignancy were identified from the Medical Data Vision database. Incident cases of non-melanoma skin cancers and non-Hodgkin lymphoma diagnosed after prescription of thiopurine and/or anti-tumor necrosis factor-α were identified between April 2008 and January 2018. Age- and sex-adjusted incidence rate ratios were calculated relative to the total treated patient population. Results A total of 75 673 eligible patients were identified at the index date. Thiopurine prescription with or without anti-tumor necrosis factor-α agents increased incidence rate ratios for non-melanoma skin cancers relative to the overall population (3.39 and 4.03, respectively). There were no notable differences in non-Hodgkin lymphoma incidence relative to the total population in any treatment subgroup, regardless of prescription of thiopurine and/or anti-tumor necrosis factor-α (all incidence rate ratios, ~1). Conclusions There is no evidence for an increased incidence of non-Hodgkin lymphoma attributable to thiopurine or anti-tumor necrosis factor-α treatment in Japanese patients with inflammatory bowel disease. The impact of racial differences on non-Hodgkin lymphoma incidences should be considered. Thiopurine therapy may be a risk factor for non-melanoma skin cancers in Japanese patients.

Long-Term Follow-Up of Targeted Biopsy Yield (LOFTY Study) in Ulcerative Colitis Surveillance Colonoscopy

“…No patient developed lymphoma, leukemia, or skin cancer during the follow-up period, while in Western countries, the risk of lymphoma is reportedly high, especially in patients on thiopurine [ 21 ]. Racial differences may exist in terms of lymphoma susceptibility; our findings may be consistent with those of previous studies [ 9 , 22 ]. A retrospective survey showed only 12 (0.11%) of the 10,500 Japanese patients with UC experienced hematologic malignancies [ 9 ].…”

“…A retrospective survey showed only 12 (0.11%) of the 10,500 Japanese patients with UC experienced hematologic malignancies [ 9 ]. Another recent large-scale study, using a nationwide administrative database in Japan, also reported only 103 (0.14%) cases of Non-Hodgkin lymphoma in 75,673 patients with UC with no increase in the incidence of lymphoma among patients on thiopurines [ 22 ].…”

Efficacy and safety of a new vedolizumab subcutaneous formulation in Japanese patients with moderately to severely active ulcerative colitis

“…Patients or their caregivers also administered SC injections during the scheduled clinic visits at Weeks 14,22,30,38,46, and 50, under the supervision of the HCP, to allow continued observation of injection technique and adverse events (AEs); while all other scheduled SC injections occurred outside of the clinic. All intravenous (IV) infusions were administered by a HCP during clinic visits at Weeks 6,14,22,30,38,and 46. HCPs had appropriate monitoring and treatment for hypersensitivity reactions available for use following administration of study drug.…”

“…For example, a recent administrative database analysis of Japanese patients with IBD found no increase in the incidence of non-Hod gkin lymphoma attributable to thiopurine treatment. 14 However, cohort studies in European patients with IBD reported an association between thiopurine treatment and an increased risk of lymphoproliferative disorders or cancer. 15,16 It remains to be determined whether the efficacy and safety of vedolizumab SC differs between patients with UC from Japanese and global populations.…”

<p>Risk of Lymphoma Associated with Anti-TNF Therapy in Patients with Inflammatory Bowel Disease: Implications for Therapy</p>

“…[20][21][22][23][24][25][26][27][28] Of those, seven included lymphoma as a separate composite outcome. 20,21,23,[25][26][27][28] Two of the seven studies had no cases of lymphoma appreciated in the ATA monotherapy group. 22,24 Of those studies that looked at lymphoma as a composite outcome and had cases in a setting of ATA monotherapy, none appreciated an increased risk of lymphoma.…”