Use of case reports and the Adverse Event Reporting System in systematic reviews: overcoming barriers to assess the link between Crohn’s disease medications and hepatosplenic T-cell lymphoma

Table 3 Medications used to treat Crohn’s disease prior to the diagnosis of hepatosplenic T-cell lymphoma (HSTCL) among unique cases

Medication	Number of cases with exposure reported, n (%) (n = 37)	Mean cumulative dose, mg (minimum - maximum)^a	Mean duration of use, years (minimum - maximum)^a	Mean number of infusions or injections (minimum - maximum)^a
Biologics	28 (76%)
Adalimumab	8 (22%)	920 (800 to 1040)	1.5 (120 days to 2.6 years)	11.5 (10 to 13)
Adalimumab	8 (22%)	n = 2	n = 2	n = 2
Infliximab^a	27 (73%)	41 (10 to 120) mg/kg	1.8 (1 day to 6 years)	9 (1 to 24)
Infliximab^a	27 (73%)	n = 7	n = 12	n = 17
Natalizumab	1 (3%)	NR	NR	3
Ustekinumab	1 (3%)	NR	NR	NR
Certolizumab pegol	0
Anti-metabolites	365 (97%)
6-mercaptopurine	20 (54%)	94,508 (3,900 to 212,160)	4.8 (39 days to 8 years)
6-mercaptopurine	20 (54%)	n = 4	n = 10
Azathioprine	23 (62%)	192,108 (1,450 to 301,125)	5.8 (39 days to 13.5 years)
Azathioprine	23 (62%)	n = 3	n = 17
Aminosalicylates	15 (41%)
Balsalazide	1 (3%)	NR	NR
Mesalamine	13 (35%)	NR	5 (n = 1)
Sulfasalazine	2 (5%)	NR	10 (n = 1)
Corticosteroids	22 (59%)
Budesonide	2 (5%)	NR	NR
Hydrocortisone	1 (3%)	NR	NR
Prednisone	14 (38%)	NR	NR
Prednisolone	5 (14%)	NR	13 (n = 1)
Corticosteroid	4 (11%)	NR	10 (n = 1)
Other medications ^b	15 (41%)
Antibiotics^c	8 (22%)	NR	NR
Cyclosporine	1 (3%)	NR	NR

^aAmong those that reported this data. Cumulative dose excludes cases that only provided mg/kg dosing but did not provide patient weight in kilograms and those cases which reported a daily dose but did not report duration of treatment. ^bExcluding vitamin/mineral supplements. ^cThe antibiotics used included ciprofloxacin, doxycycline, metronidazole, nitrofurantoin, and piperacillin/tazobactam. HSTCL, hepatosplenic T-cell lymphoma; NR, not reported.

ISSN: 2046-4053