Tocilizumab for Painful Chronic Pancreatitis

Inclusion Criteria:

• Signed informed consent.

• Probable or definitive diagnosis of CP according to the M-ANNHEIM criteria. Thisentails a typical clinical history of CP, including recurrent pancreatitis orabdominal pain in combination with the following additional criteria:

• A definitive diagnosis of CP is established by one or more of the followingadditional criteria:

• i) Pancreatic calcification

• ii) Moderate or marked ductal lesions (according to the Cambridge classification)

• iii) Exocrine pancreatic insufficiency, defined as pancreatic steatorrhea markedlyreduced by enzyme supplementation

• iv) Histological verification of CP

• A probable diagnosis of CP is established by one or more of the following additionalcriteria:

• i) Mild ductal alterations (according to the Cambridge classification)

• ii) Recurrent or persistent pseudocysts

• iii) Pathological test of pancreatic exocrine function (such as faecal elastase-1test, secretin test, secretin-pancreozymin test)

• iv) Diabetes mellitus

• Abdominal pain of presumed pancreatic origin (i.e., upper abdominal pain radiatingto the back).

• Evidence of ongoing pancreatic inflammatory activity, with an inflammatorypancreatic flare occurring one or more times within the past six months. Aninflammatory pancreatic flare is defined as an exacerbation of pancreatic pain incombination with one or more of the following criteria:

• i) Plasma amylase levels elevated 2-fold or more than the participant's usualamylase level.

• ii) Elevated plasma levels of CRP 2-fold the upper normal level without suspicion ofother sources such as infection.

• iii) Signs of pancreatic inflammation on cross-sectional imaging.

• ≥ 18 years of age

• The participant must be able to read and understand the informed consent forms.

• The participant is willing and able to comply with the scheduled visits, treatmentplan, and other trial procedures.

Exclusion Criteria:

• End-stage CP indicated by severe pancreatic atrophy defined as segmented pancreasvolume <20 ml on the latest available cross-sectional imaging examination (ComputedTomography (CT) or MRI).

• Pancreatic duct obstruction by a stricture and/or stone amendable to endoscopic orsurgical treatment. Patients with previous pancreatic duct decompression proceduresare allowed to participate.

• Ongoing alcohol or substance abuse. The patient must document abstinence fromalcohol and substance abuse for the preceding six months prior to study enrolment.Recreational alcohol consumption within the safety limits recommended by theNational Danish Health Authorities (i.e., max. ten units of alcohol per week) isallowed.

• Active or recurrent infections.

• Untreated ulcers in the gastrointestinal tract (however, those who have undergoneproper treatment and one month has elapsed with no recurrence of symptoms will notbe excluded).

• Known hypersensitivity to Tocilizumab.

• Positive test for Tuberculosis during screening

• Positive test for Hepatitis during screening

• Severe liver disease, indicated by ALT with >5 upper normal limits.

• Thrombocytopenia (platelet count < 50 x 109/L).

• Neutropenia (neutrophil count <2 x 109/L).

• Pregnancy and no contraception use, fertile women (<55 years) must provide a urinesample for pregnancy test upon inclusion.