Tocilizumab for Painful Chronic Pancreatitis

Recent independent research has emphasized the crucial role of immune cell infiltration and its interaction with pancreatic stellate cells in driving the inflammatory process and fibrogenesis in chronic pancreatitis (CP). The cytokine Interleukin 6 (IL-6) has been identified as a key mediator in this process, and preclinical studies have indicated that inhibiting IL-6 signaling can lead to favorable therapeutic outcomes. Consequently, targeting IL-6 signaling therapeutically holds great promise as a disease-modifying treatment for CP. Until now, there have been no placebo-controlled trials in humans to test immune-modulating treatments for CP. However, there have been some promising results in preclinical studies. For example, administering an anti-IL-6 receptor antibody to an animal model of CP reduced pancreatitis-related pain, indicating a potential therapeutic effect. Blocking IL-6 signaling in an in-silico model of CP was also shown to have disease-modifying effects. Recent anecdotal evidence indicates that using tocilizumab to treat patients with COVID-19 and concomitant pancreatitis can decrease inflammation and pain in the pancreas. Additionally, blocking IL-6 signaling has been demonstrated to have anti-fibrotic effects in patients with systemic sclerosis. Taken together, these findings suggest that targeting IL-6 signaling could be a promising approach for reducing inflammation and fibrogenesis in CP. Tocilizumab (RoActemra) is an anti-IL-6 receptor antibody currently used to treat several inflammatory diseases. Objectives: The investigators hypothesize that treatment with tocilizumab, compared with a placebo, will reduce symptom burden (CP-related pain) and improve physical functioning and quality of life in patients with CP. In addition, the investigators hypothesize that the clinical effects will be linked to a decrease in pancreatic inflammation and fibrosis as well as systemic inflammation. The investigators also hypothesize that the pain-relieving effect of tocilizumab will lead to the normalization of pain processing in CP patients. To test these hypotheses, the project is organized into four sub-studies. Sub-study 1 (main study - randomized placebo-controlled trial): The objective of sub-study 1 is to conduct an investigator-initiated phase 2b double-blinded, placebo-controlled, randomized clinical trial to investigate the clinical effect of tocilizumab on patient-reported outcomes. Sub-study 2 (inflammatory biomarkers): The objective of sub-study 2 is to investigate the effects of tocilizumab on systemic inflammation using blood-based immune and fibrosis markers. Sub-study 3 (quantitative imaging biomarkers): The objective of sub-study 3 is to investigate the effect of tocilizumab on pancreatic inflammation and fibrosis using Magnetic Resonance Imaging (MRI) of the pancreas. Sub-study 4 (pain processing): The objective of sub-study 4 is to investigate the effect of tocilizumab on pain processing using Pancreatic Quantitative Sensory Testing (P-QST) and electrophysiological methods (EEG and ECG).