Background/Purpose: There is limited information for the rate of hepatitis B reactivation in inflammatory arthritis patients. We conducted a systematic review and meta-analysis, assessing hepatitis B reactivation rates in patients who were with resolved or chronic hepatitis B, receiving non-biologic DMARDs, TNF-alpha inhibitors or other biologics and whether receiving antiviral prophylaxis.

Methods: We utilized the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement as the standard for protocol development. Electronic searches were conducted in Pubmed, Medline and EMBASE using OVID through 12/31/2015. A search strategy was developed for each database by combing the medical subject headings (MeSH) and/or text terms from following inclusion criteria: participants (rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, with resolved, or chronic hepatitis B infection), interventions (non-biologic DMARDs, TNF-alpha inhibitors and non-TNF biologics), and outcomes (hepatitis B reactivation). Four reviewers independently extracted study data and assessed quality of study with the Newcastle-Ottawa scales. To determine the pooled hepatitis B reactivation rate, the variances of the raw proportions were stabilized using a Freeman-Tukey-type arcsine square root transformation, using a random-effects model.

Results: 25 studies that met our inclusion criteria, including 2 case series, 10 prospective and 13 retrospective observational studies. The overall pooled rate of hepatitis B reactivation was 1.6% (table1, 95%CI, 0.8-2.6%, I²: 51.0%) in patients with resolved hepatitis B and 14.6% (95%CI, 4.3-29.0%, I²: 89.6%) in patients with chronic hepatitis B. Similar rates were observed in resolved patients on TNF-alpha inhibitors (Pooled rate: 1.4%, 95%CI, 0.5-2.6%) and non-biologic DMARDs (Pooled rate: 1.7%, 95%CI, 0.2-4.2%); whereas a higher rate was observed in other biologics users (Pooled rate: 6.1%, 95%CI, 0.0-16.6%). We also found the reactivation rate was lower in patients with chronic hepatitis B infection who received antiviral prophylaxis on TNF alpha treatments (table 2, Pooled rate: 4.4%, 95%CI, 0.4-11.7%), than those who did not (Pooled rate: 15.6%, 95%CI, 2.3-35.7%).

Conclusion: We found the hepatitis B reactivation rate in inflammatory arthritis patients was low in resolved patients and moderate in chronic hepatitis B patients. Further, higher rates were observed in chronic hepatitis B patients without antiviral prophylaxis. Table 1. HBV reactivation rates in inflammatory arthritis patients with resolved hepatitis B , on various DMARDs exposures and without antiviral prophylaxis

*Resolved HBV: HbsAg (-), HbcAb (+) **P value for study heterogeneity within drug classes. TNF: tumor necrosis factor; DMARD: Disease Modifying Anti-Rheumatic Drugs. Table 2. HBV reactivation rates in inflammatory arthritis patients with chronic hepatitis B, without or with antiviral prophylaxis

*Chronic HBV: HbsAg (+) **P value for study heterogeneity within drug classes. TNF: tumor necrosis factor; DMARD: Disease Modifying Anti-Rheumatic Drugs.