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This study aimed to evaluate the relationships between concomitant biologic disease-modifying anti-rheumatic drugs (DMARDs) and prednisolone administration and blood tacrolimus exposure or serum CYP3A4/5-related markers in rheumatoid arthritis (RA) patients without severe disease activity. Forty-six RA patients treated with oral tacrolimus once daily for maintenance of clinical remission to moderate disease activity were enrolled. The blood concentrations of tacrolimus and its major metabolite were determined at 12 h after the evening dosing. Blood samples for determination of serum markers including 4β-hydroxycholesterol (4β-OHC), 25-hydroxyvitamin D (25-OHD) and interleukin-6 (IL-6), and CYP3A5 genotype were collected. Most enrolled patients had RA with clinical remission to mild disease activity. Concomitant tocilizumab or low-dose prednisolone administration did not alter the blood tacrolimus exposure. Serum 4β-OHC level was lower in tocilizumab co-treated patients than in the biologic DMARD non-treated patients. The blood tacrolimus concentration was inversely correlated with the serum level of 25-OHD, but not 4β-OHC and IL-6. The serum level of 4β-OHC was positively associated with that of 25-OHD. No correlations were observed between the serum levels of CYP3A4/5 activity markers and IL-6. The patients with the homozygous CYP3A5*3 had the higher blood tacrolimus concentration, while CYP3A5*3 allele was not associated with the serum levels of 4β-OHC and 25-OHD. Concomitant use of tocilizumab or low-dose prednisolone had no effect on the pharmacokinetics of tacrolimus, while tocilizumab lowered serum 4β-OHC. Blood tacrolimus exposure was negatively associated with serum 25-OHD in RA patients with clinical remission to moderate disease activity. Unlabelled Image • Concomitant use of tocilizumab or prednisolone did not affect the blood tacrolimus. • Tocilizumab co-treated patients had the lower serum level of 4β-hydroxycholesterol. • Serum 25-hydroxyvitamin D negatively correlated with the blood tacrolimus. • Serum 4β-hydroxycholesterol correlated with the serum 25-hydroxyvitamin D. • CYP3A5*3 affects the blood tacrolimus in RA patients without severe disease activity. [ABSTRACT FROM AUTHOR]

To assess whether abatacept as initial biologic disease-modifying antirheumatic drug (DMARD) in the treatment of rheumatoid arthritis is associated with an increased risk of serious infections, including bone and joint, gastrointestinal, respiratory tract, skin and soft tissue, and urinary tract, when compared with other biologic DMARDs. We performed a population-based cohort study among patients newly-treated with biologic DMARDs within the US-based Truven MarketScan® population and Supplemental US Medicare from 2007 to 2014. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of serious infections requiring hospitalisation associated with initiation of abatacept, compared with initiation of other bDMARDs, after controlling for age and deciles of the propensity score. The cohort included 5,752 patients who initiated abatacept and 78,556 who initiated another biologic DMARD, of whom 193 and 1531 had a serious infection during follow-up (crude incidence rate 4.45 per 100 person-years and 3.62 per 100 person-years, respectively). Compared with other biologic DMARDs, the use of abatacept was not associated with an increased incidence of serious infections overall (HR 1.04, 95% CI 0.89–1.21). The risk did not vary by duration of use (<1 year: HR 1.03, 95% CI 0.87–1.22; >1 year: HR 1.08, 95% CI 0.77–1.52). In addition, the risk was not increased for the site-specific infections. The use of abatacept as first biologic DMARD in the treatment of rheumatoid arthritis was not associated with different risks of serious infections compared with other biologic DMARDs. [ABSTRACT FROM AUTHOR]

Background/purpose: To analyze the real-world clinical practice for the treatment of psoriatic arthritis (PsA) and to assess physicians' prescription, difficulties in diagnosis, therapeutic strategy, rationales for biologic therapies and unmet needs in Taiwan.Methods: We conducted a nationwide cross-sectional observational study by face-to-face in depth interviews with 50 rheumatologists and 30 dermatologists who took care of patients with PsA.Results: The major procedures for recognizing PsA included joint, skin and nail examinations, radiographic imaging, and medical history. More dermatologists established the diagnosis when psoriatic patients with arthritis didn't present with rheumatoid factors (p < 0.05). For milder arthritis, physicians tended to prescribe etanercept in combination with conventional disease-modifying antirheumatic drugs (DMARDs). The efficacy, safety, retention rate, and non-parenteral administration are the major concerns of physicians which are also the primary unmet needs in the current management of PsA.Conclusion: This survey showed the status quo in Taiwan of the clinical management for PsA including diagnostic difficulties, therapeutic consideration, rationales for biologic DMARDs selection and unmet needs in treatment. It has indicated that interdisciplinary collaboration may further improve the quality for PsA care. These results may help establish new strategy to develop next generation biologics. [ABSTRACT FROM AUTHOR]

Objectives: Hepatitis B (HBV) infection, which is prevalent worldwide, is also frequently seen in patients with rheumatoid arthritis (RA). The Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) endorsed a national consensus process to review the available evidence on HBV management in RA patients and to produce practical, hospital-wide recommendations.Methods: The consensus panel consisted of infectious disease consultants, rheumatologists and epidemiologists and used the criteria of the Oxford Center for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations.Results: A core-set of statements has been developed to help clinicians in the management of patients with RA and HBV infection. Vaccination and prophylaxis of RA patients treated with biological drugs have been also discussed.Conclusions: HBV infection is not rare in clinical practice; a screening for HBV in all patients with early arthritis is not universally accepted, while it is considered mandatory before starting any immunosuppressive or hepatotoxic treatment. In fact, a specific risk, associated with the use of biologic treatments, exists for patients with HBV infection, although longitudinal studies of viral reactivation are generally reassuring. RA patients with HBV infection should be referred to the hepatologist and correctly classified into active or inactive carriers. Patients with active hepatitis B should undergo antiviral treatment before starting immunosuppressive treatments. Occult HBV carriers should be monitored or receive prophylaxis on the basis of the risk of reactivation associated with the administered treatment. [ABSTRACT FROM AUTHOR]

Objectives To estimate the incidence of tuberculosis (TB) in rheumatoid arthritis (RA) patients treated with tumor necrotizing factor inhibitor (TNFI) and evaluate the safety of resuming biologic disease-modifying anti-rheumatic drugs (DMARDs) in patients who developed TB after anti-TNF treatment. Methods We conducted an inception cohort study of RA patients in the Korean Healthcare Claims Database who started TNFI as the first biologic DMARD between January 2009 and December 2013. The incidence rate (IR) of TB was estimated among total TNFI starters and a nested case–control analysis was performed to compare the characteristics of patients who developed TB and those did not. Patients diagnosed with relapsed TB after resuming biologic DMARDs were identified and their features were described. Results We included 4638 RA patients who started TNFI, contributing 8542 PYs of follow-up. The IR of TB in TNFI users was 1.10 (CI: 0.86–1.34) per 100 PYs. After the initial 6 months, the IR was highest at 1.56 (CI: 1.02–2.10) and decreased gradually over time. Among the 81 patients who developed TB, 30 patients (37.0%) resumed biologic DMARDs with a mean interval of 3.3 months after TB development. Two cases of TB were detected among 30 patients with an observational period of 45.7 PY. Conclusions The IR of TB in RA patients who started TNFI was 1.10 per 100 PYs. This rate was highest during the first 6 months. Resumption of biologic DMARDs requires careful monitoring for TB relapse. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This study compared the incidence and hazard of ICD-9-CM-coded infections and severe infections in rheumatoid arthritis (RA) patients treated with subsequent-line (SL) BIOs (BIO) after switching from first-line (FL) anti-TNF therapy (anti-TNF). Methods: Retrospective analysis of a large U.S. claims database. RA patients initiating an FL anti-TNF between 1/1/2004 and 3/31/2010 were identified and followed forward in time to capture all SL BIO episodes through 3/31/2010. SL BIO episodes were classified into: abatacept, adalimumab, etanercept, infliximab, or rituximab. Multivariate mixed-effects survival models compared the hazard of infections and severe infections across the SL BIO episodes with adjustment for demographic and clinical confounders. Results: In total, 4332 SL BIO episodes were identified: mean age 55 years; 80% female. In adjusted analyses: when compared to rituximab, the hazard of all infections was significantly higher for adalimumab (hazard ratio [HR] = 1.31, 95% confidence interval [CI] = 1.09–1.55), etanercept (HR = 1.44, 95% CI = 1.20–1.72), and infliximab (HR = 1.30, 95% CI = 1.07–1.57), and insignificantly different for abatacept (HR = 1.18, 95% CI = 0.98–1.41); when compared to rituximab, the hazard of severe infection was significantly higher for infliximab (HR = 1.62, 95% CI = 1.03–2.55), and insignificantly different for abatacept (HR = 1.21, 95% CI = 0.78–1.88), adalimumab (HR = 1.10, 95% CI = 0.72–1.68), and etanercept (HR = 1.27, 95% CI = 0.83–1.95). Conclusions: In RA patients treated with SL BIO, a 30–44% higher hazard of all infection was observed in anti-TNFs versus rituximab with a 62% higher hazard of severe infection observed in infliximab versus rituximab. This study used a non-randomized, observational design and is therefore subject to confounding from unmeasured factors that influence both treatment choice and infection risk. [Copyright &y& Elsevier]

Objectives: To compare the patterns of American College of Rheumatology (ACR) response between tocilizumab and other biologic agents in patients with rheumatoid arthritis who have inadequate response to disease-modifying antirheumatic drugs (DMARD-IR). Methods: Systematic literature review identified similarly designed double-blind, randomized, placebo-controlled trials over an 18-year period that investigated the effectiveness of abatacept (2), rituximab (2), and TNF-α inhibitors etanercept, infliximab, and adalimumab (11) in DMARD-IR patients; data from 3 placebo-controlled, phase 3 trials for tocilizumab, a newly developed IL-6 inhibitor, were included. The endpoint of interest was ACR20/50/70 response criteria at 24 to 30 weeks. Results were analyzed simultaneously using Bayesian mixed-treatment comparison techniques. Nonoverlapping ACR response rates (ACR70) for each agent were compared among treatments to identify differences in ACR response pattern. Separate analyses of overlapping ACR20/50/70 responses were conducted to identify the source of any differences. Results were expressed as relative risk of ACR20/50/70 response and associated 95% credible interval (CrI). Results: Patterns across nonoverlapping ACR response levels varied significantly across treatments. In subsequent analyses, the effectiveness of tocilizumab appeared to be comparable to that of other biologic agents for ACR20 and ACR50 responses but greater for ACR70. Specifically, tocilizumab had greater ACR70 responses than both TNF-α inhibitors (relative risk = 1.8; CrI = 1.2, 2.6) and abatacept (relative risk = 2.0; CrI = 1.3, 3.1). Conclusions: Among DMARD-IR patients, tocilizumab shows a pattern of response that differs from that of other biologic agents. Post-hoc analyses suggest that the difference lies in a higher likelihood of ACR70 response with tocilizumab. [Copyright &y& Elsevier]