Risk of Hepatitis B Virus Reactivation in Patients With Inflammatory Arthritis Receiving Disease‐Modifying Antirheumatic Drugs: A Systematic Review and Meta‐Analysis

Lin, Tzu‐Chieh; Yoshida, Kazuki; Tedeschi, Sara K.; Abreu, Mirhelen Mendes de; Hashemi, Nikroo; Solomon, Daniel H.

doi:10.1002/acr.23346

Cited by 34 publications

(24 citation statements)

References 48 publications

(151 reference statements)

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“…In contrast, none of HBsAg‐positive patients who had received pre‐emptive antiviral therapy developed rHBV. Our data support previous findings that antiviral therapy can reduce the incidence or severity of rHBV . As Hsu et al showed that in a computerized alert system providing excellent HBV screening and effectively preventing rHBV in cancer patients receiving chemotherapy, HBV screening is needed, and antiviral therapy should be given in HBsAg‐positive patients before starting RTX therapy.…”

Section: Discussionsupporting

confidence: 90%

Reactivation of hepatitis B virus infection following rituximab treatment in HBsAg‐negative, HBcAb‐positive rheumatoid arthritis patients: A long‐term, real‐world observation

et al. 2019

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Aim: Longitudinal data of the reactivation of hepatitis B virus (rHBV) and serial serological markers or HBV-DNA has been limited. This study aimed to investigate the temporal course of rHBV development in rheumatoid arthritis (RA) patients undergoing long-term rituximab therapy. Methods: The occurrence of rHBV was examined in 157 RA patients during rituximab therapy. Serum levels of HBV surface antigen (HBsAg), HBV core antibody (HBcAb), and HBsAb were determined by electrochemiluminescence immunoassays, and viral loads by real-time polymerase chain reaction assay. Results: Among 157 patients undergoing rituximab therapy, 103 (65.6%) were HBsAg-negative and HBcAb-positive. Before rituximab therapy, 20 (19.4%) of these 103 patients were HBsAb-negative, while 83 (80.1%) were HBsAb-positive. Five (20%) HBsAb-negative patients developed rHBV after rituximab therapy. Among 83 HBsAb-positive patients, 4 (4.8%) developed rHBV. Among 9 patients with rHBV, 7 (77.7%) exhibited HBsAg seroreversion. Significant decline of HBsAb titers (mean ± SD, 296.0 ± 417.3 mIU/mL at baseline vs 187.0 ± 332.5 mIU/mL after rituximab therapy, P < 0.001) was observed in HBsAg-/HBsAb + patients. All HBsAgnegative patients who developed rHBV during rituximab therapy were characterized by baseline HBsAb titers < 100 mIU/mL and negative HBsAb at the time of rHBV.HBsAb positivity was an independent protective factor for rHBV (hazards ratio: 0.14, 95% CI: 0.03-0.62, P = 0.009). Conclusion:Baseline HBsAb positivity was a significant protective factor for rHBV in HBsAg-negative, HBcAb-positive RA patients receiving rituximab therapy. K E Y W O R D SHBsAg seroreversion, hepatitis B virus reactivation, rheumatoid arthritis, rituximab therapy

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Section: Discussionsupporting

confidence: 90%

Reactivation of hepatitis B virus infection following rituximab treatment in HBsAg‐negative, HBcAb‐positive rheumatoid arthritis patients: A long‐term, real‐world observation

et al. 2019

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“…Besides their well-established role in ameliorating control of disease activity, bDMARDs have been associated with safety concerns. Infections (including tuberculosis and opportunistic) [ 14 , 15 ], skin cancers [ 16 ], demyelinating leukoencephalopathy [ 17 ] and hepatitis B reactivation [ 18 ] have been reported during therapy with bDMARDs in clinical trials and real-life studies.…”

Section: Introductionmentioning

confidence: 99%

Implementing a simple pharmacovigilance program to improve reporting of adverse events associated with biologic therapy in rheumatology: Preliminary results from the Calabria Biologics Pharmacovigilance Program (CBPP)

et al. 2018

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IntroductionPost-marketing surveillance activities (namely pharmacovigilance) are crucial to favor the early detection of unexpected adverse events (AEs) and/or serious adverse reactions (SAEs). Indeed, spontaneous reporting of AEs has been demonstrated to underestimate the number of events in different clinical settings. Aim of the present study is to report the preliminary data of a Regional (Calabria, Italy) Pharmacovigilance Program (CBPP) aimed at improving AEs’ reporting associated with biologics use in rheumatology.Materials and methodsWe developed a simple, cost-effective pharmacovigilance program based on regular training sessions for physicians (stimulated reporting), periodical phone calls by a clinical pharmacologist aimed at identifying new events and stimulating self-awareness and encouraging reporting to the physician during the subsequent follow-up visit for minor AEs. To test this approach, all consecutive patients undergoing treatment with one biologic agent at eight rheumatology centers during a two-years period were invited to participate. Collected AEs were compared to the number of AEs spontaneously reported for the same molecules in the same centers before starting the protocol.ResultsDuring the study period, 399 patients (245 females; mean age: 58 ± 11 years) were started on treatment with biologics for active RA (n = 211, 52.9%), PsA (n = 119, 29.8%) or AS (n = 69, 17.3%) at eight rheumatology centers. A total of 125 AEs (31.3%) and 9 SAEs (2.3%) were reported during the two-years study period. In the control cohort (comprising 368 consecutive patients started on treatment with bDMARDs during a two-years period before CBPP study) only 42 (11.4%) AEs and no SAEs were reported (p < 0.0001). The most common AEs were injection site reactions and skin disorders.ConclusionsIn conclusion, our study provides further evidence of a critical role of active pharmacovigilance in detection, reporting and analysis of AEs in rheumatology.

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“…Therefore, inhibition of TNF can lead to enhanced viral replication, leading to reactivation in resolved HBV/occult HBV infection (HBV surface antigen [HBsAg] negative and antibody to HBV core antigen positive) and in inactive carriers (HBsAg positive, HBV e‐antigen negative, anti‐HBe positive, with viral loads <2000 IU/mL and normal range of alanine aminotransferase [ALT]) or worsening of the active disease (HBsAg positive, with viral loads >2000 IU/mL and with constant or periodic ALT increase). The most recent meta‐analysis of observational studies found the rate of HBV reactivation in inflammatory arthritis patients with resolved hepatitis B after TNF inhibitor treatment (n = 629) to be 1.4%, similar to the rate during nonbiologic DMARDs treatment (1.7%) . In a group of patients with chronic HBV infection (inactive carriers and with active disease), rates of reactivation/disease worsening significantly differ among those who received simultaneously with TNF inhibitor prophylaxis/treatment for HBV (n = 57) and those who did not (n = 64; 4.4% vs 15.6%, respectively).…”

Section: Infectionsmentioning

confidence: 92%

“…The most recent meta-analysis of observational studies found the rate of HBV reactivation in inflammatory arthritis patients with resolved hepatitis B after TNF inhibitor treatment (n = 629) to be 1.4%, similar to the rate during nonbiologic DMARDs treatment (1.7%). 52 In a group of patients with chronic HBV infection (inactive carriers and with active disease), rates of reactivation/disease worsening significantly differ among those who received simultaneously with TNF inhibitor prophylaxis/treatment for HBV (n = 57) and those who did not (n = 64; 4.4% vs 15.6%, respectively). It is hard, however, to estimate rates of HBV reactivations after TNF inhibitors in patients with ankylosing spondylitis.…”

Section: Viral Hepatitismentioning

confidence: 96%

The Safety Profile of Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis: Are TNF Inhibitors Safer Than We Thought?

Wroński

Fiedor

2018

The Journal of Clinical Pharma

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Tumor necrosis factor (TNF) inhibitors significantly improved the treatment options for patients with ankylosing spondylitis. Unfortunately, currently, there is no strategy for sustaining remission of the disease with TNF inhibitors; after discontinuation, a high percentage of patients experience flares in a short time. Therefore, up‐to‐date, long‐term use of TNF inhibitors in patients with ankylosing spondylitis remains necessary. For this reason, the issue of the long‐term safety of TNF inhibitors in patients with ankylosing spondylitis raises concerns. Although TNF inhibitors are well established in ankylosing spondylitis treatment, the majority of studies on TNF inhibitors’ safety have been performed in patients with rheumatoid arthritis. Until recently, there were very few studies of TNF inhibitors’ safety in ankylosing spondylitis. Meanwhile, TNF inhibitors appear to have different safety profiles in ankylosing spondylitis and rheumatoid arthritis. In this review, we describe available data on the occurrence of adverse events associated with TNF inhibitor treatment in ankylosing spondylitis, including serious adverse events, infections, serious infections, tuberculosis, opportunistic infections, hepatitis B reactivation, malignancies, laboratory test abnormalities, autoimmune diseases, paradoxical adverse events, and heart failure.

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Risk of Hepatitis B Virus Reactivation in Patients With Inflammatory Arthritis Receiving Disease‐Modifying Antirheumatic Drugs: A Systematic Review and Meta‐Analysis

Abstract: We found that the HBV reactivation rate in inflammatory arthritis patients receiving DMARDs was low in resolved patients and moderate in patients with chronic HBV infection. Further, lower rates were observed in patients with chronic HBV infection who were using antiviral prophylaxis.

Cited by 34 publications

References 48 publications

Reactivation of hepatitis B virus infection following rituximab treatment in HBsAg‐negative, HBcAb‐positive rheumatoid arthritis patients: A long‐term, real‐world observation

Reactivation of hepatitis B virus infection following rituximab treatment in HBsAg‐negative, HBcAb‐positive rheumatoid arthritis patients: A long‐term, real‐world observation

Implementing a simple pharmacovigilance program to improve reporting of adverse events associated with biologic therapy in rheumatology: Preliminary results from the Calabria Biologics Pharmacovigilance Program (CBPP)

The Safety Profile of Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis: Are TNF Inhibitors Safer Than We Thought?

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