Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment
Background & Aims
Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens.
Methods
We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP.
Results
We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054–3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818–1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427–0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose.
Conclusions
Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.
Background
Type 1 autoimmune pancreatitis is a rare immune-mediated disease. There are no large-scale studies in European patients, and evidence on the optimum steroid treatment regimen is lacking.
Findings
Induction of complete remission occurred irrespective of the starting dose or starting dose duration. Early relapse occurred irrespective of the steroid tapering duration, induction treatment duration, and total cumulative dose.
Implications for patient care
To achieve complete remission, a steroid starting dose of 0.4 mg/kg/day with a minimum of 20 mg, for 2 weeks, followed by a tapering regimen less than 12 weeks was effective. We found no evidence to support a higher starting dose, longer starting dose duration, or long taper period.
Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas.
Currently, 2 subtypes have been established.
Type 1 AIP is the pancreatic manifestation of IgG4-related disease.
Currently, 2 subtypes have been established.
Type 1 AIP is the pancreatic manifestation of IgG4-related disease.
Type 2 AIP is known as idiopathic duct-centric pancreatitis and is limited to the pancreas.
Type 1 is more common than type 2, and represents more than 90% of patients diagnosed with AIP.
Type 2 AIP might be overlooked, because there is no serologic marker available, making a histologic specimen essential for a definite diagnosis.
Several diagnostic scoring systems have been proposed during the past few decades, based on a combination of clinical, radiologic, serologic, and pathologic characteristics, until eventually the International Consensus Diagnostic Criteria (ICDC) were developed.
Besides type 1 and type 2 AIP, the ICDC defines a third group of individuals who do not fulfill the criteria for either type, the so-called not-otherwise-specified (NOS) AIP.
The standard therapy for AIP is steroids, with a very high response rate (>95% of case)
Consensus guidelines recommend treatment with an initial dose of prednisone 0.6–1.0 mg/kg/day with a minimum of 20 mg/day, for 2–4 weeks, to induce remission. Afterward, it is recommended to gradually taper the dose, with a total treatment duration of at least 12 weeks.
As an alternative to steroids, several studies have shown good results for rituximab, albeit in small numbers of patients.After inducing remission of the disease, relapses are seen in around 30% of patients with type 1 AIP, and only in 9% of patients with type 2.
For relapses, it is recommended to readminister steroids.
However, the level of evidence supporting the previously mentioned treatment recommendations is generally low.
As an alternative to steroids, several studies have shown good results for rituximab, albeit in small numbers of patients.After inducing remission of the disease, relapses are seen in around 30% of patients with type 1 AIP, and only in 9% of patients with type 2.
For relapses, it is recommended to readminister steroids.
However, the level of evidence supporting the previously mentioned treatment recommendations is generally low.
e pan-European cohort of patients with type 1 AIP; and to compare the effectiveness of different steroid treatment regimens. Our secondary objectives were: to identify factors associated with successful remission induction; and to compare the effectiveness of steroids and rituximab in treating relapse of disease.
Figure 1 Complete remission stratified on elevation of IgG4 level. ULN, upper limit of normal.
