Risk Factors for Rate of Relapse and Effects of Steroid Maintenance Therapy in Patients With Autoimmune Pancreatitis: Systematic Review and Meta-analysis

Abstract

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e64. Learning Objective-Upon completion of this activity, successful learners will be able to choose critically the exams that should be performed to diagnose autoimmune pancreatitis; recognize, diagnose, and describe possible other organ involvement in patients with IgG4-related autoimmune pancreatitis; and select the most appropriate test in the evaluation of suspected exocrine pancreatic insufficiency. BACKGROUND & AIMS:Risk for relapse after induction of remission with steroid therapy has been studied extensively in patients with autoimmune pancreatitis (AIP), but findings have been equivocal. We performed a systematic review and meta-analysis to estimate the relapse rate of AIP after initial remission after steroid treatment and to identify factors associated with relapse. METHODS:Three reviewers searched MEDLINE, SCOPUS, and EMBASE until July 2018 to identify studies on rate of relapse of AIP after induction of remission with steroid therapy. A pooled estimate was calculated using the DerSimonian and Laird method for a random-effects model. This study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS:Thirty-six studies met the inclusion criteria for meta-analysis. The median follow-up time was 40.8 months. Fifty-two percent of patients were classified as having type 1 AIP. The pooled estimate of relapse rate was 33% (95% CI, 30%-37%). A higher proportion of patients with type 1 AIP had a relapse compared with patients with type 2 AIP (37.5% vs 15.9%; P < .001). We found significant heterogeneity among studies (P < .01). Long-term maintenance therapy with steroids and study quality were associated independently with AIP relapse, after we adjusted for year of publication by multivariate meta-regression. CONCLUSIONS:In a systematic review and meta-analysis, we found that a large proportion of patients with AIP treated successfully with steroid induction therapy had a relapse (33%)-particularly patients with type 1 AIP (37%). Maintenance steroid therapy lasting longer than 1 year could reduce risk of relapse. However, the data characterizing relapse rates are of limited quality, indicating the need for randomized controlled trials and new immunosuppressive drugs.

Multicentric Italian survey on daily practice for autoimmune pancreatitis: Clinical data, diagnosis, treatment, and evolution toward pancreatic insufficiency

“…Regarding the employed therapeutic approach, surgery was performed in 11% of patients, in the majority for suspicion of pancreatic cancer, and most of the patients received steroids as initial treatment and as maintenance therapy, with a very high response rate, as previously documented. 31 Immunosuppressants and rituximab were used especially after relapses, even if rarely; only a small number of patients received azathioprine as first-line treatment, because other comorbidities contraindicated the use of steroids. Both immunosuppressive drugs and rituximab deserve to be further explored in randomized studies, in particular rituximab, which in a recent retrospective study on relapsing autoimmune pancreatitis looked very promising, having been shown to be more efficient than immunosuppressant drugs, and with better tolerance.…”

Risk factors and treatment of relapses in autoimmune pancreatitis: Rituximab is safe and effective

“…A recent meta-analysis on risk factors including 36 studies also demonstrates that type 1 AIP has a higher relapse rate (37.5% vs 15.9%; p < 0.01). 23 Tacelli et al highlight the controversial results between the different studies. Jaundice was the most common significant risk factor for AIP in multivariate analysis.…”

Steroid Therapy and Steroid Response in Autoimmune Pancreatitis

“…As mentioned above, relapse occurs in 24-52% of type 1 AIP cases [22,29,[72][73][74][79][80][81][136][137][138][139][140][141][142][143][144] and 0-27% of type 2 AIP cases [21,73,78] after cessation of corticosteroid treatment or dose tapering of corticosteroids. Identification of characteristics or risk factors for relapse is critical, as unnecessary steroid treatment in patients in whom recurrence is unlikely should be avoided.…”

“…To date, several factors for predicting AIP relapse have been reported. These include a high level of serum IgG4 [22,79]; extrapancreatic lesions [78,80,136,137], especially proximal bile duct stenosis [73,136,138]; retroperitoneal fibrosis [139]; dacryoadenitis/sialadenitis [140]; jaundice [141]; discontinuation of steroid therapy [138,142,143]; a small reduction in the level of serum sIgG4 3-4 months after steroid initiation [80,81]; and a low level of pancreatic shrinkage following steroid treatment [144]. Maintenance corticosteroid therapy, with or without steroid-sparing agents, is recommended for type 1 AIP patients with factors predictive of relapse, although the therapeutic period is unclear.…”