Different Risk of Tuberculosis and Efficacy of Isoniazid Prophylaxis in Rheumatoid Arthritis Patients with Biologic Therapy: A Nationwide Retrospective Cohort Study in Taiwan

Abstract

Increasing evidence indicates an increased risk of tuberculosis (TB) for rheumatoid arthritis (RA) patients receiving biologic therapy, and the effectiveness of isoniazid prophylaxis (INHP) in TB prevention. We aimed to examine 1) the incidence rate (IR) and risk factors for TB among RA patients receiving different therapies; 2) INHP effectiveness for TB prevention; 3) mortality rates after TB diagnosis in patients receiving different therapies. This retrospective study was conducted using a nationwide database: 168,720 non-RA subjects and a total of 42,180 RA patients including 36,162 csDMARDs-exposed, 3,577 etanercept-exposed, 1,678 adalimumab-exposed and 763 rituximab-exposed patients. TB risk was 2.7-fold higher in RA cohort compared with non-RA group, with an adjusted hazard ratio (aHR) of 2.58. Advanced age, male, the use of corticosteroids≧5mg/day, and the presence of diabetes mellitus (DM), chronic obstructive pulmonary disease and chronic kidney disease were risk factors for developing TB. Using csDMARDs-exposed group as reference, aHR of TB was the highest with adalimumab treatment (1.52), followed by etanercept (1.16), and the lowest with rituximab (0.08). INHP could effectively reduce TB risk in biologics-exposed patients. Mortality rates after TB diagnosis were higher in RA patients, particularly the elderly and those with DM, with lower rates in adalimumab-exposed patients compared with csDMARDs-exposed patients. In conclusion, TB risk was increased in patients receiving TNF-α inhibitors, but the risk associated with rituximab therapy was relatively low. With the effectiveness of INHP shown in the prevention of biologics-associated TB, stricter implementation of INHP should be beneficial. The mortality from biologics–associated TB may be efficiently reduced through increased awareness.

Real‐world effectiveness and safety of rituximab in the treatment of rheumatoid arthritis: A single‐center experience in Taiwan

“…In the present investigation, we have not found reactivation of latent tuberculosis infection (LTBI) although some of the patients did have positive IGRA and underwent prophylactic therapy with isoniazid. Although RA patients have a 2.7‐fold increase in the risk of developing TB, our findings are in agreement with those reported previously in that there were no increased risks of TB infection after RTX therapy . Since RTX has no significant effect on release of interferon‐γ in RA patients with LTBI, it is conceivable that RTX exerts it effect through a signal transduction pathway other than Th1 inhibition or innate immune suppression …”

Tofacitinib in the treatment of moderate-to-severe rheumatoid arthritis: a cost-effectiveness analysis compared with adalimumab in Taiwan

“…MTX dosage in local practice ranges from 7.5-15 mg in accordance with the APLAR RA treatment recommendations 11 ; MTX dosage used in the model was 10 mg/week. Adalimumab was selected as the comparator, as it is a commonly prescribed bDMARD for the second-line treatment of this patient population in Taiwan 12 .…”

“…7.5-15 mg weekly), in accordance with the Asia Pacific League of Associations for Rheumatology (APLAR) RA treatment recommendations 11 . In Taiwan, bDMARDs that are currently approved for use in patients with RA include the tumor necrosis factor inhibitors (TNFi) adalimumab, etanercept (both approved in 2002), and golimumab (approved in 2012), the B-cell depleting anti-CD20 antibody rituximab (approved in 2011), the interleukin-6 receptor antibody tocilizumab, and the T-cell co-stimulatory modulator abatacept (both approved in 2012) 12 . The TNFi certolizumab pegol was approved in 2016 and was, therefore, not available in Taiwan at the time of this analysis.…”

“…Of these, adalimumab and etanercept are the most commonly prescribed bDMARDs for second-line treatment (i.e. after failure of csDMARDs) in Taiwan 12 . Although the introduction of bDMARDs has substantially improved outcomes for many patients with RA, there remains an unmet need for new agents that allow a greater proportion of patients to reach treatment goals and produce longer-lasting responses than currently available therapies, and that are easily administered and cost-effective 13,14 .…”

The Efficacy and Safety of Rituximab in Rheumatoid Arthritis: New Evidence

“…Ретроспективное когортное исследование (National Health Insurance Research Database) было посвящено изуче-нию риска развития туберкулеза на фоне терапии РА [31]. В исследование вошли 3577 пациентов, получавших ЭТЦ, и 1678 -АДА в комбинации с МТ, а 763 пациента с неэф-фективностью или непереносимостью иФНОα получали РТМ.…”