Pediatric Drug‐Associated Pancreatitis Reveals Concomitant Risk Factors and Poor Reliability of Causality Scoring: Report From INSPPIRE

Drug‐associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co‐risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE‐2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE‐2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children. Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non‐Medication cases, and ARP‐Med vs CP‐Med groups. Naranjo score was calculated for each DAP episode. Of 726 children, 392 had ARP and 334 had CP; 51 children (39 ARP and 12 CP) had ≥1 AP associated with a medication; 61% had ≥1 AP without concurrent medication exposure. The Med group had other risk factors present (where tested): 10 of 35 (28.6%) genetic, 1 of 48 (2.1%) autoimmune pancreatitis, 13 of 51 (25.5%) immune‐mediated conditions, 11 of 50 (22.0%) obstructive/anatomic, and 28 of 51 (54.9%) systemic risk factors. In Med group, 24 of 51 (47%) had involvement of >1 medication, simultaneously or over different AP episodes. There were 20 ARP and 4 CP cases in “probable” category and 19 ARP and 7 CP in “possible” category by Naranjo scores. Medications were involved in 51 of 726 (7%) of ARP or CP patients in INSPPIRE‐2 cohort; other pancreatitis risk factors were present in most, suggesting a potential additive role of different risks. The Naranjo scoring system failed to identify any cases as “definitive,” raising questions about its reliability for DAP.