Risk factors for losing hepatitis B virus surface antibody in patients with HBV surface antigen negative/surface antibody positive serostatus receiving biologic disease-modifying anti-rheumatic drugs: a nested case-control study

Abstract Background: Hepatitis B virus (HBV) reactivation consequent to immunosuppressive therapy is an increasingly prevalent problem with serious clinical implications. Treatment with biologic agents conduces to the loss of protective antibody to HBV surface antigen (anti-HBs), which significantly increases the risk of HBV reactivation. Hence, we investigated the risk factors for losing anti-HBs in patients with rheumatic diseases and HBV surface antigen negative/anti-HBs positive (HBsAg-/anti-HBs+) serostatus during treatment with biologic disease-modifying anti-rheumatic drugs (DMARDs). Methods: Using a nested case-control design, we prospectively enrolled patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis/psoriasis, or juvenile idiopathic arthritis, who were treated with biologic DMARDs at Changhua Christian Hospital, Taiwan, from January 2013 to June 2019 and had HBsAg-/anti-HBs+ serostatus; the analytic sample excluded all patients with HBsAg+ or anti-HBs- serostatus. Anti-HBs titers were monitored 6-monthly and cases were defined as anti-HBs < 10 mIU/ml during follow-up. Cases were matched one- to-all with controls with anti-HBs ≥ 10 mIU/ml on the same ascertainment date and equivalent durations of biologic DMARDs treatment (control patients could be resampled and could also become cases during follow-up). Between-group characteristics were compared and risk factors for anti-HBs loss were investigated by conditional logistic regression analyses. Results: Among 294 eligible patients, 23 cases were matched with 311 controls. The incidence of anti-HBs loss was ∼ 2.7%/person-year during biologic DMARDs treatment. Besides lower baseline anti-HBs titer (risk ratio 0.93, 95% CI 0.89-0.97), cases were significantly more likely than controls to have diabetes mellitus (risk ratio 4.76, 95% CI 1.48-15.30) and chronic kidney disease (risk ratio 14.00, 95% CI 2.22-88.23) in univariate analysis. Risk factors remaining significantly associated with anti-HBs loss in multivariate analysis were lower baseline anti-HBs titer (adjusted risk ratio 0.93, 95% CI 0.88-0.97) and chronic kidney disease (adjusted risk ratio 45.68, 95% CI 2.39-871.5). Conclusions: Besides lower baseline anti-HBs titer, chronic kidney disease also strongly predicts future anti-HBs negativity in patients with HBsAg-/anti-HBs+ serostatus who receive biologic DMARDs to treat rheumatic diseases. Patients with low anti-HBs titer (≤ 100 mIU/ml) and/or chronic kidney disease should be monitored during biologic DMARDs therapy, to enable timely prophylaxis to preempt potential HBV reactivation.

Colombian Association of Rheumatology. Consensus on recommendations to decrease and discontinue biological therapy in patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis / Asociación Colombiana de Reumatología. Consenso sobre recomendaciones para disminución y descontinuación de la terapia biológica en pacientes con artritis reumatoide, espondilitis anquilosante y artritis psoriásica

A B S T R A C T Objective: The objective of this study was to establish recommendations for the reduction and discontinuation of biological disease-modifying antirheumatic drugs, with the aim of becoming a guide document for health professionals involved in the management of patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Materials and methods: The recommendations were established through consensus by a panel of experts in rheumatology, and based on the analysis of available scientific evidence obtained from systematic reviews and the clinical experience of the panellists. Results: A total of 33 rheumatoid arthritis related studies were included, with 6 psoriatic arthritis related, and 9 ankylosing Spondylitis related. The recommendations for the reduction of biological therapies were made by establishing a plan to determine when and how to reduce the biological disease-modifying antirheumatic drugs in patients with these 3 diseases, and in some cases lead to the discontinuation of these treatments. Conclusion: The recommendations established in this document will serve as a guide to improve the efficiency of biological therapy in these diseases, reduce the variability in clinical practice, and establish an adequate risk/benefit ratio.

RESUMEN Objetivo: El objetivo de este estudio fue establecer recomendaciones para la disminución y descontinuación de la terapia biológica con el fin de que se convierta en un documento guía para los profesionales de la salud involucrados en el manejo de pacientes con artritis reumatoide, espondilitis anquilosante y artritis psoriásica. Materiales y métodos: Las recomendaciones fueron establecidas mediante consenso desarrollado a través de un panel de expertos en reumatología, basado en el análisis de la evidencia científica disponible obtenida de revisiones sistemáticas y sobre la experiencia clínica de los panelistas. Resultados: Se incluyeron 33 estudios relacionados con artritis reumatoide, 6 de artritis psoriásica y 9 de espondilitis anquilosante. Las recomendaciones para la disminución de las terapias biológicas se realizaron estableciendo un plan para determinar cuándo y cómo reducir los fármacos biológicos modificadores de enfermedades reumáticas en pacientes con estas 3 enfermedades y en algunos casos conducir a la descontinuación de estos tratamientos. Conclusión: Las recomendaciones establecidas en este documento servirán de guía para mejorar la eficiencia de la terapia biológica en estas enfermedades, reducir la variabilidad en la práctica clínica y establecer de manera adecuada una relación riesgo/beneficio.

Cost-Minimization Analysis of Biologic Disease-Modifying Antirheumatic Drugs Administered by Subcutaneous Injections in Patients with Rheumatoid Arthritis

BACKGROUND: The subcutaneous formulation of biologic disease-modifying antirheumatic drugs (DMARDs) was preferred due to favored self-administration and would be an economical treatment option for patients with rheumatoid arthritis. This study was to compare the economic impact of biologic DMARDs administered by subcutaneous injection in patients with rheumatoid arthritis who had inadequate response to conventional DMARDs. METHODS: The cost-minimization analysis was conducted to estimate the lifetime health care costs of treatment sequences with subcutaneous biologic DMARDs as first-line therapy from a health care system perspective. The Markov model was developed to represent the transitions through treatment sequences based on American College of Rheumatology response rate and discontinuation rate. The health care costs comprised the cost of medications, administration, dispensing, outpatient visits, test/diagnostic examination, palliative therapy and treatment of serious infection. All costs were expressed in 2016 Korean Won (KRW) and discounted at 5%. RESULTS: The mean lifetime health care cost per patient was lowest in the etanercept sequence, which was estimated at KRW 63,441,679. The incremental costs of the treatment sequence started with adalimumab, golimumab, abatacept, and tocilizumab were KRW 7,985,730, KRW 4,064,669, KRW 2,869,947, and KRW 4,282,833, respectively, relative to etanercept sequence. These differences in costs mainly were attributable to medication costs. One-way and probabilistic sensitivity analyses confirmed that etanercept represented the option with the lowest cost compared with comparators. CONCLUSION: This study found that etanercept is likely a cost-saving treatment option among subcutaneous biologic DMARDs in patients with rheumatoid arthritis.

Comparative Effectiveness of Biologic DMARDs in Rheumatoid Arthritis Patients with Inadequate Response to conventional DMARDs: Using a Bayesian Network Meta-analysis

BACKGROUND: Biologic disease-modifying antirheumatic drugs (bDMARDs) extend the treatment choices for rheumatoid arthritis patients with insufficient response or intolerance to conventional DMARDs (cDMARDs). These agents have considerable efficacy compared with conventional DMARDs, but only a few head-to-head comparisons among these agents have been performed. The objective of this systematic review and network meta-analysis (NMA) was to compare the relative efficacy of Certolizumab with conventional DMARD to licensed bDMARD with cDMARD therapy for patients who failed to prior cDMARD treatment under the condition of the reimbursement coverage criteria in Korea. METHODS: A systematic review was conducted using MEDLINE and Cochrane library. Key endpoints were the American College of Rheumatology (ACR) responses of 20/50/70 at six months. Bayesian outcomes were calculated as median of treatment effect, probability of the best, Odds Ratio (OR) and probability that OR was greater than one. RESULTS: Compared with other bDMARDs, Certolizumab were associated with higher or comparable ACR response rates; in ACR20, the OR (probability of OR>1) was 2.08 (92.6%) for Adalimumab, 1.86 (85.7%) for Etanercept, 1.89 (79.5%) for Golimumab, 2.36 (92.1%) for Infliximab, 1.79 (87.0%) for Abatacept, 1.74 (80.8%) for Rituximab and 1.82 (86.8%) for Tocilizaumab. In ACR50 and ACR70, the ORs did not present significant differences. CONCLUSION: Certolizaumab with cDMARD was more effective or comparable than other bDMARDs in patients who failed prior cDMARD treatment.