sj-docx-1-taj-10.1177_20406223231168488 – Supplemental material for Lifetime risk, life expectancy, loss-of-life expectancy, and lifetime healthcare expenditures for psoriasis in Taiwan: a nationwide cohort followed from 2000 to 2017

Supplemental material, sj-docx-1-taj-10.1177_20406223231168488 for Lifetime risk, life expectancy, loss-of-life expectancy, and lifetime healthcare expenditures for psoriasis in Taiwan: a nationwide cohort followed from 2000 to 2017 by Hsien-Yi Chiu, Joung-Liang Lan and Ying-Ming Chiu in Therapeutic Advances in Chronic Disease</p

Commensurate incidence and outcomes of liver enzyme elevation between anti-tumor necrosis factor users with or without prior hepatitis B virus infections

<div><p>Background and objective</p><p>Potential hepatoxicity is an important clinical concern when administering immunosuppressive therapies to patients infected by hepatitis B virus (HBV). Tumor necrosis factor inhibitors (anti-TNF) increase the likelihood of hepatitis consequent to HBV reactivation, but reported risks and outcomes vary. We determined the risks of liver enzyme elevation in anti-rheumatic drug users from an HBV-endemic region with differing HBV serostatus.</p><p>Methods</p><p>We established retrospective cohorts with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis who: 1) received anti-TNF agents from 1 January 2004 to 30 June 2013; 2) received care from 1 June 2011 to 30 June 2013 but only ever used conventional disease-modifying anti-rheumatic drugs (DMARDs). Serology results defined three subgroups: HBV surface antigen positive (HBsAg+), HBsAg negative/HBV core antibody positive (HBsAg−/HBcAb+), or uninfected. We compared incidences of serum alanine aminotransferase (ALT) exceeding twice the upper reference limit between HBV serostatus subgroups in each treatment cohort.</p><p>Results</p><p>Among 783 patients treated with anti-TNF (n = 472) or DMARDs only (n = 311), HBsAg−/HBcAb+ anti-TNF users had incidence of ALT elevation commensurate with uninfected counterparts (6.1 vs. 6.0/100 person-years), compared to 19.6/100 person-years in HBsAg+ patients (standardized rate ratio 3.3, 95% CI 1.3–8.2); none effected had severe or fatal hepatitis and ALT levels in all HBsAg−/HBcAb+ patients remained stable, mostly normalizing spontaneously, or after moderating treatment. Patterns of of ALT elevation associated with differing HBV serostatus in the DMARD cohort, resembled those in anti-TNF users.</p><p>Conclusions</p><p>In this large HBV-endemic cohort, the absolute incidence of ALT elevation in anti-TNF users was more than three-fold higher in HBsAg+ patients than in uninfected counterparts; however, no such association was evident in patients with HBsAg−/HBcAb+ serotype, whose risk and outcomes of liver enzyme elevation were similar to uninfected patients, suggesting that anti-TNF use by HBsAg−/HBcAb+ patients is probably safe.</p></div

Incidence of liver enzyme elevation in anti-TNF cohort patients with different HBV serostatus.

<p>Incidence of liver enzyme elevation in anti-TNF cohort patients with different HBV serostatus.</p

Characteristics of the DMARD cohort.

<p>Characteristics of the DMARD cohort.</p

Clinical status of patients with abnormal liver function during anti-TNF therapy.

<p>Clinical status of patients with abnormal liver function during anti-TNF therapy.</p

Demographic profile of the cohort patients.

<p>Demographic profile of the cohort patients.</p

Incidence of liver enzyme elevation in DMARD cohort patients with different HBV serostatus.

<p>Incidence of liver enzyme elevation in DMARD cohort patients with different HBV serostatus.</p

Characteristics of the anti-TNF cohort.

<p>Characteristics of the anti-TNF cohort.</p

The frequency of LTFU in the four rheumatic diseases.

<p>*The p value (chi-squared test) evaluated the association between the four rheumatic diseases and being potential LTFU. The percentage (%) represent the proportion of follow-up status in each disease. The frequency of LTFU is represented by braces. RFU: regularly follow-up, LTFU: lost to follow-up.</p

Traced reasons for LTFU.

<p>The figure illustrates the proportion of the reasons for LTFU in the four rheumatic diseases.</p