Time and dose-dependent effect of systemic glucocorticoids on major adverse cardiovascular event in patients with rheumatoid arthritis: a population-based study.

OBJECTIVES: Cardiovascular event (CVE) risk in rheumatoid arthritis (RA) was increased by glucocorticoids (GC) use. Whether there is a threshold dose and duration of GC use beyond which will increase CVE rate remains controversial. We studied the time-varying effect of GC and its dose on the risk of incident major adverse cardiovascular events (MACE) in patients with RA. METHODS: Patients with RA without MACE at baseline were recruited from a Hong Kong citywide database from 2006 to 2015 and followed till 2018. The primary outcome was the first occurrence of an MACE. Cox regression and inverse probability treatment weighting analyses with time-varying covariates were used to evaluate the association of GC and MACE, adjusting for demographics, traditional CV risk factors, inflammatory markers and the usage of antirheumatic drugs. RESULTS: Among 12 233 RA patients with 105 826 patient-years of follow-up and a mean follow-up duration of 8.7 years, 860 (7.0%) developed MACE. In the time-varying analyses after controlling for confounding factors, a daily prednisolone dose of ≥5 mg significantly increased the risk of MACE (erythrocyte sedimentation rate model: HR 2.02, 95% CI 1.72 to 2.37; C reactive protein model: HR 1.87, 95% CI 1.60 to 2.18), while a daily dose below 5 mg was not associated with MACE risk, compared with no GC use. In patients receiving daily prednisolone ≥5 mg, the risk of incident MACE was increased by 7% per month. CONCLUSIONS: GC was associated with a duration and dose-dependent increased risk of MACE in patients with RA. Very low dose prednisolone (<5 mg daily) did not appear to confer excessive CV risk.

Five-year cardiovascular event risk in early rheumatoid arthritis patients who received treat-to-target management: a case-control study.

OBJECTIVES: This study explored whether the excess cardiovascular (CV) disease (CVD) risk in RA could be ameliorated by suppression of inflammation using a treat-to-target (T2T) approach. We compared the CV event (CVE) incidence among ERA patients managed by a T2T strategy with a CV risk factor-matched non-RA population and a historical RA cohort (HRA). METHODS: This was an observational study using the city-wide hospital data and the ERA registry. ERA patients received T2T management while HRA patients received routine care. Each ERA/HRA patient was matched to three non-RA controls according to age, gender and CV risk factors. Patients on antiplatelet/anticoagulant agents, with pre-existing CVD, chronic kidney disease or other autoimmune diseases were excluded. All subjects were followed for up to 5 years. The primary end point was the first occurrence of a CVE. RESULTS: The incidence of CVE in the ERA cohort (n = 261) and ERA controls were similar with a hazard ratio of 0.53 (95% CI 0.15, 1.79). In contrast, the incidence of CVE in the HRA cohort (n = 268) was significantly higher than that of the HRA controls with a hazard ratio of 1.9 (95% CI 1.16, 3.13). The incidence of CVE in the ERA cohort was significantly lower than that of the HRA cohort and the difference became insignificant after adjusting for inflammation, the use of methotrexate and traditional CV risk factors. CONCLUSION: ERA patients managed by a T2T strategy did not develop excess CVE compared with CV risk factor-matched controls over 5 years.

Risk of alanine aminotransferase flare in patients with previous hepatitis B virus exposure on biological modifier therapies-A population-based study.

BACKGROUND: It is uncertain whether biological therapies would increase the risk of hepatitis among patients with past hepatitis B virus (HBV) infection. This study aimed to evaluate the risk of alanine aminotransferase (ALT) flare in patients with past HBV infection while using biological therapies. METHODOLOGY: Patients who received biological therapies for ≥3 months from 2000 to 2019 were identified from a population-based database in Hong Kong. Patients with past HBV infection were compared with a control group without prior HBV exposure. The primary endpoint was development of ALT flare within 5 years of starting biological therapies, defined as ALT >80 IU/L. RESULTS: There were 2471 and 2394 patients with and without past HBV infection respectively. There was a non-significant increase in risk of ALT flare among the HBV-exposed group (27.6% vs. 23.7%, p = .055). In multivariable analysis, using prednisolone-equivalent dose of >20 mg daily, male sex and concomitant immunosuppressants were risk factors for ALT flare. The risk of ALT flare was significantly higher with anti-CD20 when compared to other biological agents (36.1% vs. 14.5%, p < .01), but was not significantly different among anti-tumour necrosis factor, anti-cytokine, Janus kinase inhibitors and T cell/B cell inhibitors or anti-integrin (15.2% vs. 14.6% vs. 11.7% vs. 11.1%, p = .82). Among patients with documented hepatitis B surface antigen seroreversion, 96% were on anti-CD20. CONCLUSIONS: Our study further supports the current suggestion of prophylactic anti-viral before starting anti-CD20 in HBV-exposed patients. While other biological therapies appear to have a lower risk for ALT flare, this result needs further confirmation.