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 4 Results of the published instruments assessing causal relationship between medication exposure and adverse events when applied to patients in this case series

Medication(s)	Naranjo score	Kramer score	WHO score
Biologics
Adalimumab	Possible	Possible	Possible
Certolizumab pegol	No use reported in any case report
Infliximab	Possible	Possible	Possible
Natalizumab	Possible	Possible	Possible
Ustekinumab	Possible	Possible	Possible
Anti-metabolites
6-mercaptopurine	Possible	Possible	Possible
Azathioprine	Possible	Possible	Possible
Aminosalicylates
Balsalazide	Possible	Unlikely	Possible
Mesalamine	Possible	Unlikely	Possible
Sulfasalazine	Possible	Unlikely	Possible
Corticosteroids
Budesonide	Possible	Unlikely	Possible
Hydrocortisone	Possible	Unlikely	Possible
Prednisone	Possible	Unlikely	Possible
Prednisolone	Possible	Unlikely	Possible
Corticosteroid unspecified	Possible	Unlikely	Possible
Other medications
Cyclosporine	Possible	Possible	Possible
Metronidazole	Possible	Unlikely	Possible
Nitrofurantoin	Possible	Unlikely	Possible
Piperacillin/tazobactam	Possible	Unlikely	Possible
Doxycycline	Possible	Unlikely	Possible
Ciprofloxacin	Possible	Unlikely	Possible

Possible, all cases reporting that medication received a score of ‘possible’ using that particular causality assessment; unlikely, all cases reporting that medication received a score of ‘unlikely’ using that particular causality assessment. WHO, World Health Organization.