Dataset Information

The seroconversion rate of QuantiFERON-TB Gold In-Tube test in psoriatic patients receiving secukinumab and ixekizumab, the anti-interleukin-17A monoclonal antibodies.

ABSTRACT: BACKGROUND:For psoriatic patients receiving biologics, the concern of tuberculosis (TB) infection exists. Although the TB risk of anti-interleukin (IL)-17A agents is generally considered very low, more real-world data are needed to support the safety. OBJECTIVES:This study aims to provide the real-world experience of using serial QuantiFERON-TB Gold In-Tube (QFT-GIT) test among patients treated with secukinumab or ixekizumab in Taiwan, an intermediate TB burden country, for the detection of latent TB infection (LTBI) reactivation or newly acquired TB infection. METHODS:This retrospective review evaluated 100 consecutive patients with psoriasis receiving anti-IL-17A therapies who were checked with at least twice QFT-GIT between 2016 and 2019 in National Taiwan University Hospital, Taipei and Hsin-Chu, Taiwan. RESULTS:Among the 100 patients, the baseline QFT-GIT results were negative in 81.0% (81/100), positive in 18.0% (18/100), and indeterminate in 1.0% (1/100) of patients. The overall outcomes in patients receiving at least 6 months of cumulative exposure to anti-IL-17A agents were persistently seronegative in 80 patients (80.0%), persistently seropositive in 14 patients (14.0%), seroconversion in 1 patient (1.0%), seroreversion in 3 patients (3.0%), and others in 2 patients (2.0%). In patients with at least 11 months of cumulative exposure, the seroconversion rate was 1.3% (1/79). The only case with seroconversion had a positive QFT-GIT result previously. No case of TB reactivation or newly acquired TB infection was identified during the follow-up. CONCLUSIONS:In patients treated with anti-IL-17A monoclonal antibodies for psoriasis, routine serial repeat QFT-GIT testing was associated with lower seroconversion rate compared to real-world data of tumor necrosis factor-? inhibitors and anti-IL-12/23 antibody in Taiwan and in pivotal studies. Because clinical TB symptoms and signs are often preceded by QFT-GIF seroconversion, this result further supports the safety of anti-IL-17A agents in patients with psoriasis for LTBI.

SUBMITTER: Wu CY

PROVIDER: S-EPMC6934285 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The seroconversion rate of QuantiFERON-TB Gold In-Tube test in psoriatic patients receiving secukinumab and ixekizumab, the anti-interleukin-17A monoclonal antibodies.

Wu Chen-Yu CY Chiu Hsien-Yi HY Tsai Tsen-Fang TF

PloS one 20191227 12

<h4>Background</h4>For psoriatic patients receiving biologics, the concern of tuberculosis (TB) infection exists. Although the TB risk of anti-interleukin (IL)-17A agents is generally considered very low, more real-world data are needed to support the safety.<h4>Objectives</h4>This study aims to provide the real-world experience of using serial QuantiFERON-TB Gold In-Tube (QFT-GIT) test among patients treated with secukinumab or ixekizumab in Taiwan, an intermediate TB burden country, for the de ...[more]

PMID: 31881026

Similar Datasets

Project description:BackgroundThe QuantiFERON®-TB Gold In-Tube test (QFT-GIT) is a viable alternative to the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection. However, within-subject variability may limit test utility. To assess variability, we compared results from the same subjects when QFT-GIT enzyme-linked immunosorbent assays (ELISAs) were performed in different laboratories.MethodsSubjects were recruited at two sites and blood was tested in three labs. Two labs used the same type of automated ELISA workstation, 8-point calibration curves, and electronic data transfer. The third lab used a different automated ELISA workstation, 4-point calibration curves, and manual data entry. Variability was assessed by interpretation agreement and comparison of interferon-? (IFN-?) measurements. Data for subjects with discordant interpretations or discrepancies in TB Response >0.05 IU/mL were verified or corrected, and variability was reassessed using a reconciled dataset.ResultsNinety-seven subjects had results from three labs. Eleven (11.3%) had discordant interpretations and 72 (74.2%) had discrepancies >0.05 IU/mL using unreconciled results. After correction of manual data entry errors for 9 subjects, and exclusion of 6 subjects due to methodological errors, 7 (7.7%) subjects were discordant. Of these, 6 (85.7%) had all TB Responses within 0.25 IU/mL of the manufacturer's recommended cutoff. Non-uniform error of measurement was observed, with greater variation in higher IFN-? measurements. Within-subject standard deviation for TB Response was as high as 0.16 IU/mL, and limits of agreement ranged from -0.46 to 0.43 IU/mL for subjects with mean TB Response within 0.25 IU/mL of the cutoff.ConclusionGreater interlaboratory variability was associated with manual data entry and higher IFN-? measurements. Manual data entry should be avoided. Because variability in measuring TB Response may affect interpretation, especially near the cutoff, consideration should be given to developing a range of values near the cutoff to be interpreted as "borderline," rather than negative or positive.

Project description:QuantiFERON®-TB Gold in-tube (QFT-GIT) supernatants may be important samples for use in assessment of anti-tuberculosis (TB) antibodies when only limited volumes of blood can be collected and when a combination of antibody and cytokine measurements are required. These analytes, when used together, may also have the potential to differentiate active pulmonary TB (APTB) from latent TB infection (LTBI). However, few studies have explored the use of QFT-GIT supernatants for investigations of antibody responses. This study determined the correlation and agreement between anti-CFP-10 and anti-ESAT-6 antibody concentrations in QFT-GIT nil supernatant and serum pairs from 68 TB household contacts. We also explored the ability of Mycobacterium tuberculosis (M.tb) specific antibodies, or ratios of antibody to interferon gamma (IFN-γ) in QFT-GIT supernatants, to differentiate 97 APTB cases from 58 individuals with LTBI. Sputum smear microscopy was used to define APTB, whereas the QFT-GIT and tuberculin skin test were used to define LTBI. There were strong and statistically significant correlations between anti-CFP-10 and anti-ESAT-6 antibodies in unstimulated QFT-GIT supernatants and sera (r = 0.89; p<0.0001 for both), and no significant differences in antibody concentration between them. Anti-CFP-10 & anti-ESAT-6 antibodies differentiated APTB from LTBI with sensitivities of 88.7% & 71.1% and specificities of 41.4% & 51.7% respectively. Anti-CFP-10 antibody/M.tb specific IFN-γ and anti-ESAT-6 antibody/M.tb specific IFN-γ ratios had sensitivities of 48.5% & 54.6% and specificities of 89.7% and 75.9% respectively. We conclude that QFT-GIT nil supernatants may be used in the place of sera when measuring antibody responses, reducing blood volumes needed for such investigations. Antibodies in QFT-GIT nil supernatants on their own discriminate APTB from LTBI with high sensitivity but have poor specificity, whereas the reverse is true when antibodies are used in combination with M.tb specific cytokines. Further antibody and antibody/cytokine combinations need to be explored to achieve better diagnostic accuracy.

Project description:OBJECTIVE:To conduct a cost-effectiveness analysis from the perspective of the Spanish National Health System (NHS) comparing ixekizumab versus secukinumab. DESIGN:A Markov model with a lifetime horizon and monthly cycles was developed based on the York model. Four health states were included: a biological disease-modifying antirheumatic drug (bDMARD) induction period of 12 or 16?weeks, maintenance therapy, best supportive care (BSC) and death. Treatment response was assessed based on both Psoriatic Arthritis Response Criteria (PsARC) and ?90% improvement in the Psoriasis Area Severity Index score (PASI90). At the end of the induction period, responders transitioned to maintenance therapy. Non-responders and patients who discontinued maintenance therapy transitioned to BSC. Clinical efficacy data were derived from a network meta-analysis. Health utilities were generated by applying a regression analysis to Psoriasis Area Severity Index and Health Assessment Questionnaire?Disability Index scores collected in the ixekizumab SPIRIT studies. Results were subject to extensive sensitivity and scenario analysis. SETTING:Spanish NHS. PARTICIPANTS:A hypothetical cohort of bDMARD-naïve patients with psoriatic arthritis and concomitant moderate-to-severe psoriasis was modelled. INTERVENTIONS:Ixekizumab and secukinumab. RESULTS:Ixekizumab performed favourably over secukinumab in the base-case analysis, although cost savings and quality-adjusted life-year (QALY) gains were modest. Total costs were €153?901 compared with €156?559 for secukinumab (difference -€2658). Total QALYs were 9.175 vs 9.082 (difference 0.093). Base-case results were most sensitive to the annual bDMARD discontinuation rate and the modification of PsARC and PASI90 response to ixekizumab or secukinumab. CONCLUSION:Ixekizumab provided more QALYs at a lower cost than secukinumab, with differences being on a relatively small scale. Sensitivity analysis showed that base-case results were generally robust to changes in most input parameters. TRIAL REGISTRATION NUMBER:SPIRIT-P1: NCT01695239; Post-results, SPIRIT-P2: NCT02349295; Post-results.

Project description:BackgroundWorld Health Organization (WHO) recommends systematic screening of high-risk populations, including household contacts (HHCs) of adult pulmonary tuberculosis (TB) patients, as a key strategy for elimination of TB. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and tuberculin skin test (TST) are two commonly used tools for the detection of latent tuberculosis infection (LTBI) but may yield differential results, affecting eligibility for TB preventive therapy.Materials and methodsA prospective cohort study of adult pulmonary TB patients and their HHCs were recruited in 2 cities of India, Pune and Chennai. HHCs underwent QFT-GIT (QIAGEN) and TST (PPD SPAN 2TU/5TU). A positive QFT-GIT was defined as value ?0.35 IU/ml and a positive TST as an induration of ?5 mm. A secondary outcome of TST induration ?10mm was explored. Proportion positive by either or both assays, discordant positives and negatives were calculated; test concordance was assessed using percentage agreement and kappa statistics; and risk factors for concordance and discordance including age categories were assessed using logistic regression. Sensitivity and specificity was estimated by latent class model.ResultsOf 1048 HHCs enrolled, 869 [median (IQR) age: 27 years (15-40)] had both TST and QFT-GIT results available and prevalence of LTBI by QFT-GIT was 54% [95% CI (51, 57)], by TST was 55% [95% CI (52, 58)], by either test was 74% [95% CI (71, 77) and by both tests was 35% [95% CI (31, 38)]. Discordance of TST+/QFT-GIT- was 21% while TST-/QFT-GIT+ was 26%. Poor to fair agreement occurred with TST 5mm or 10mm cutoff (60 and 61% agreement with kappa value of 0.20 and 0.25 respectively). Test agreement varied by age, TST strength and induration cut-off. In multivariate analysis, span PPD was a risk factor for QFT-GIT+ and TST- while absence of BCG scar was for TST+ and QFT-GIT-. Being employed and exposure to TB case outside the household case were associated with positivity by both the tests. Sensitivity of TST and QFT-GIT to diagnose LTBI was 77% and 69%. Probability of having LTBI was >90% when both tests were positive irrespective of exposure gradient.ConclusionPrevalence of LTBI among HHCs of adult pulmonary TB patients in India is very high and varies by test type, age, and exposure gradient. In our high TB burden setting, a strategy to treat all HHCs or a targeted strategy whereby an exposure index is used should be assessed in future preventive therapy and vaccine studies as HHCs have several factors that place them at high risk for progression to TB disease.

Dataset Information

The seroconversion rate of QuantiFERON-TB Gold In-Tube test in psoriatic patients receiving secukinumab and ixekizumab, the anti-interleukin-17A monoclonal antibodies.

Publications

The seroconversion rate of QuantiFERON-TB Gold In-Tube test in psoriatic patients receiving secukinumab and ixekizumab, the anti-interleukin-17A monoclonal antibodies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets