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Article ; Online: Exploring Risks of Human Challenge Trials For COVID-19.

Manheim, David / Wiȩcek, Witold / Schmit, Virginia / Morrison, Josh

Risk analysis : an official publication of the Society for Risk Analysis

2021 Volume 41, Issue 5, Page(s) 710–720

Abstract: Human challenge trials (HCTs) are a potential method to accelerate development of vaccines and therapeutics. However, HCTs for COVID-19 pose ethical and practical challenges, in part due to the unclear and developing risks. In this article , we introduce ...

Abstract	Human challenge trials (HCTs) are a potential method to accelerate development of vaccines and therapeutics. However, HCTs for COVID-19 pose ethical and practical challenges, in part due to the unclear and developing risks. In this article , we introduce an interactive model for exploring some risks of a severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) dosing study, a prerequisite for any COVID-19 challenge trials. The risk estimates we use are based on a Bayesian evidence synthesis model which can incorporate new data on infection fatality risks (IFRs) to patients, and infer rates of hospitalization. The model estimates individual risk, which we then extrapolate to overall mortality and hospitalization risk in a dosing study. We provide a web tool to explore risk under different study designs. Based on the Bayesian model, IFR for someone between 20 and 30 years of age is 15.1 in 100,000, with a 95% uncertainty interval from 11.8 to 19.2, while risk of hospitalization is 130 per 100,000 (100-160). However, risk will be reduced in an HCT via screening for comorbidities, selecting lower-risk population, and providing treatment. Accounting for this with stronger assumptions, we project the fatality risk to be as low as 2.5 per 100,000 (1.6-3.9) and the hospitalization risk to be 22.0 per 100,000 (14.0-33.7). We therefore find a 50-person dosing trial has a 99.74% (99.8-99.9%) chance of no fatalities, and a 98.9% (98.3-99.3%) probability of no cases requiring hospitalization.
MeSH term(s)	Antiviral Agents/therapeutic use ; Bayes Theorem ; COVID-19/prevention & control ; COVID-19/therapy ; COVID-19/transmission ; COVID-19/virology ; COVID-19 Vaccines/therapeutic use ; Ethics, Research ; Humans ; Risk Assessment ; SARS-CoV-2/isolation & purification
Chemical Substances	Antiviral Agents ; COVID-19 Vaccines
Language	English
Publishing date	2021-05-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	778660-8
ISSN	1539-6924 ; 0272-4332
ISSN (online)	1539-6924
ISSN	0272-4332
DOI	10.1111/risa.13726
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Article ; Online: Vaccines at Velocity: Evaluating Potential Lives Saved by Earlier Vaccination in the COVID-19 Pandemic

Wiecek, Witold / Johnston, David / Dulka, Tomas / Toomey, Danny / Lewis, Enlli

medRxiv

Abstract: Fast development of COVID-19 vaccines likely averted millions of deaths. We estimate how many more lives could have been saved if safe and effective vaccines were available earlier in the pandemic, in particular, before the epidemic waves in winter of ... ...

Abstract	Fast development of COVID-19 vaccines likely averted millions of deaths. We estimate how many more lives could have been saved if safe and effective vaccines were available earlier in the pandemic, in particular, before the epidemic waves in winter of 2020. We fit an epidemiological model informed by retrospective data and simulate counterfactual vaccination scenarios for the United Kingdom and the United States in which vaccines are available between 30 and 90 days earlier. We find that up to 1 July 2021 reductions in mortality range from 10,000 to 48,000 in the UK and 53,000 to 130,000 in the US, depending on when vaccinations start. This corresponds to a maximum of 7.1 and 4 deaths averted per 10,000 people in the UK and US respectively. We find that our model is sensitive to uncertain vaccine parameters and benefits depend on the time horizon of the analysis. However, the large average reductions we estimate suggests that it is highly cost-effective to make large investments in strategies to expedite vaccine availability.
Keywords	covid19
Language	English
Publishing date	2023-06-20
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.06.16.23291442
Database	COVID19

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Article ; Online: Mapping Interindividual Variability of Toxicodynamics Using High-Throughput Transcriptomics and Primary Human Hepatocytes from Fifty Donors.

Niemeijer, Marije / Więcek, Witold / Fu, Shuai / Huppelschoten, Suzanna / Bouwman, Peter / Baze, Audrey / Parmentier, Céline / Richert, Lysiane / Paules, Richard S / Bois, Frederic Y / van de Water, Bob

Environmental health perspectives

2024 Volume 132, Issue 3, Page(s) 37005

Abstract: Background: Understanding the variability across the human population with respect to toxicodynamic responses after exposure to chemicals, such as environmental toxicants or drugs, is essential to define safety factors for risk assessment to protect the ...

Abstract	Background: Understanding the variability across the human population with respect to toxicodynamic responses after exposure to chemicals, such as environmental toxicants or drugs, is essential to define safety factors for risk assessment to protect the entire population. Activation of cellular stress response pathways are early adverse outcome pathway (AOP) key events of chemical-induced toxicity and would elucidate the estimation of population variability of toxicodynamic responses. Objectives: We aimed to map the variability in cellular stress response activation in a large panel of primary human hepatocyte (PHH) donors to aid in the quantification of toxicodynamic interindividual variability to derive safety uncertainty factors. Methods: High-throughput transcriptomics of over 8,000 samples in total was performed covering a panel of 50 individual PHH donors upon 8 to 24 h exposure to broad concentration ranges of four different toxicological relevant stimuli: tunicamycin for the unfolded protein response (UPR), diethyl maleate for the oxidative stress response (OSR), cisplatin for the DNA damage response (DDR), and tumor necrosis factor alpha ( Results: Transcriptome mapping allowed the investigation of the interindividual variability in concentration-dependent stress response activation, where the average of BMCs had a maximum difference of 864-, 13-, 13-, and 259-fold between different PHHs for UPR, OSR, DDR, and Discussion: Overall, by combining high-throughput transcriptomics and population modeling, improved understanding of interindividual variability in chemical-induced activation of toxicity relevant stress pathways across the human population using a large panel of plated cryopreserved PHHs was established, thereby contributing toward increasing the confidence of
MeSH term(s)	Humans ; Hepatocytes ; Gene Expression Profiling ; Transcriptome ; Oxidative Stress
Language	English
Publishing date	2024-03-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	195189-0
ISSN	1552-9924 ; 0091-6765 ; 1078-0475
ISSN (online)	1552-9924
ISSN	0091-6765 ; 1078-0475
DOI	10.1289/EHP11891
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Article ; Online: Nivolumab versus Cabozantinib: Comparing Overall Survival in Metastatic Renal Cell Carcinoma.

Wiecek, Witold / Karcher, Helene

PloS one

2016 Volume 11, Issue 6, Page(s) e0155389

Abstract: Renal-cell carcinoma (RCC) affects over 330,000 new patients every year, of whom 1/3 present with metastatic RCC (mRCC) at diagnosis. Most mRCC patients treated with a first-line agent relapse within 1 year and need second-line therapy. The present study ...

Abstract	Renal-cell carcinoma (RCC) affects over 330,000 new patients every year, of whom 1/3 present with metastatic RCC (mRCC) at diagnosis. Most mRCC patients treated with a first-line agent relapse within 1 year and need second-line therapy. The present study aims to compare overall survival (OS) between nivolumab and cabozantinib from two recent pivotal studies comparing, respectively, each one of the two emerging treatments against everolimus in patients who relapse following first-line treatment. Comparison is traditionally carried out using the Bucher method, which assumes proportional hazard. Since OS curves intersected in one of the pivotal studies, models not assuming proportional hazards were also considered to refine the comparison. Four Bayesian parametric survival network meta-analysis models were implemented on overall survival (OS) data digitized from the Kaplan-Meier curves reported in the studies. Three models allowing hazard ratios (HR) to vary over time were assessed against a fixed-HR model. The Bucher method favored cabozantinib, with a fixed HR for OS vs. nivolumab of 1.09 (95% confidence interval: [0.77, 1.54]). However, all models with time-varying HR showed better fits than the fixed-HR model. The log-logistic model fitted the data best, exhibiting a HR for OS initially favoring cabozantinib, the trend inverting to favor nivolumab after month 5 (95% credible interval <1 from 10 months). The initial probability of cabozantinib conferring superior OS was 54%, falling to 41.5% by month 24. Numerical differences in study-adjusted OS estimates between the two treatments remained small. This study evidences that HR for OS of nivolumab vs. cabozantinib varies over time, favoring cabozantinib in the first months of treatment but nivolumab afterwards, a possible indication that patients with poor prognosis benefit more from cabozantinib in terms of survival, nivolumab benefiting patients with better prognosis. More evidence, including real-world observational data, is needed to compare effectiveness between cabozantinib and nivolumab.
MeSH term(s)	Anilides/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/therapeutic use ; Bayes Theorem ; Carcinoma, Renal Cell/diagnosis ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/mortality ; Humans ; Kidney Neoplasms/diagnosis ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/mortality ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/mortality ; Pyridines/therapeutic use ; Survival Analysis ; Treatment Outcome
Chemical Substances	Anilides ; Antibodies, Monoclonal ; Antineoplastic Agents ; Pyridines ; cabozantinib (1C39JW444G) ; nivolumab (31YO63LBSN)
Language	English
Publishing date	2016
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Meta-Analysis
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0155389
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Article ; Online: Exploring Risks of Human Challenge Trials for COVID-19

Manheim, David / Wiecek, Witold / Schmit, Virginia / Morrison, Josh

medRxiv

Abstract: Human Challenge Trials (HCTs) are a potential method to accelerate development of vaccines and therapeutics. However, HCTs for COVID-19 pose ethical and practical challenges, in part due to the unclear and developing risks. In this paper, we introduce an ...

Abstract	Human Challenge Trials (HCTs) are a potential method to accelerate development of vaccines and therapeutics. However, HCTs for COVID-19 pose ethical and practical challenges, in part due to the unclear and developing risks. In this paper, we introduce an interactive model for exploring some risks of a SARS-COV-2 dosing study, a prerequisite for any COVID-19 challenge trials. The risk estimates we use are based on a Bayesian evidence synthesis model which can incorporate new data on infection fatality rates (IFRs) to patients, and infer rates of hospitalization. We have also created a web tool to explore risk under different study design parameters and participant scenarios. Finally, we use our model to estimate individual risk, as well as the overall mortality and hospitalization risk in a dosing study. Based on the Bayesian model we expect IFR for someone between 20 and 30 years of age to be 17.5 in 100,000, with 95% uncertainty interval from 12.8 to 23.6. Using this estimate, we find that a simple 50-person dosing trial using younger individuals has a 99.1% (95% CI: 98.8% to 99.4%) probability of no fatalities, and a 92.8% (95% CI: 90.3% to 94.6%) probability of no cases requiring hospitalization. However, this IFR will be reduced in an HCT via screening for comorbidities, as well as providing medical care and aggressive treatment for any cases which occur, so that with stronger assumptions, we project the risk to be as low as 3.1 per 100,000, with a 99.85% (95% CI: 99.7% to 99.9%) chance of no fatalities, and a 98.7% (95% CI: 97.4% to 99.3%) probability of no cases requiring hospitalization.
Keywords	covid19
Language	English
Publishing date	2020-11-26
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.11.19.20234658
Database	COVID19

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Article ; Online: Testing fractional doses of COVID-19 vaccines.

Więcek, Witold / Ahuja, Amrita / Chaudhuri, Esha / Kremer, Michael / Simoes Gomes, Alexandre / Snyder, Christopher M / Tabarrok, Alex / Tan, Brandon Joel

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 8

Abstract: Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in parallel in multiple approaches to accelerating vaccination. We argue there are high expected social returns to ... ...

Abstract	Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in parallel in multiple approaches to accelerating vaccination. We argue there are high expected social returns to investigating the scope for lowering the dosage of some COVID-19 vaccines. While existing evidence is not dispositive, available clinical data on the immunogenicity of lower doses combined with evidence of a high correlation between neutralizing antibody response and vaccine efficacy suggests that half or even quarter doses of some vaccines could generate high levels of protection, particularly against severe disease and death, while potentially expanding supply by 450 million to 1.55 billion doses per month, based on supply projections for 2021. An epidemiological model suggests that, even if fractional doses are less effective than standard doses, vaccinating more people faster could substantially reduce total infections and deaths. The costs of further testing alternative doses are much lower than the expected public health and economic benefits. However, commercial incentives to generate evidence on fractional dosing are weak, suggesting that testing may not occur without public investment. Governments could support either experimental or observational evaluations of fractional dosing, for either primary or booster shots. Discussions with researchers and government officials in multiple countries where vaccines are scarce suggests strong interest in these approaches.
MeSH term(s)	COVID-19/immunology ; COVID-19/mortality ; COVID-19/prevention & control ; COVID-19/virology ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/economics ; COVID-19 Vaccines/supply & distribution ; Developed Countries ; Developing Countries ; Drug Administration Schedule ; Humans ; Immunization, Secondary/economics ; Immunization, Secondary/methods ; Models, Statistical ; Off-Label Use ; SARS-CoV-2/drug effects ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Survival Analysis ; Vaccination/economics ; Vaccination/methods
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2022-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2116932119
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Article ; Online: Inter-phenotypic differences in CYP2C9 and CYP2C19 metabolism: Bayesian meta-regression of human population variability in kinetics and application in chemical risk assessment.

Quignot, Nadia / Więcek, Witold / Lautz, Leonie / Dorne, Jean-Lou / Amzal, Billy

Toxicology letters

2020 Volume 337, Page(s) 111–120

Abstract: Quantifying variability in pharmacokinetics (PK) and toxicokinetics (TK) provides a science-based approach to refine uncertainty factors (UFs) for chemical risk assessment. In this context, genetic polymorphisms in cytochromes P450 (CYPs) drive inter- ... ...

Abstract	Quantifying variability in pharmacokinetics (PK) and toxicokinetics (TK) provides a science-based approach to refine uncertainty factors (UFs) for chemical risk assessment. In this context, genetic polymorphisms in cytochromes P450 (CYPs) drive inter-phenotypic differences and may result in reduction or increase in metabolism of drugs or other xenobiotics. Here, an extensive literature search was performed to identify PK data for probe substrates of the human polymorphic isoforms CYP2C9 and CYP2C19. Relevant data from 158 publications were extracted for markers of chronic exposure (clearance and area under the plasma concentration-time curve) and analysed using a Bayesian meta-regression model. Enzyme function (EF), driven by inter-phenotypic differences across a range of allozymes present in extensive and poor metabolisers (EMs and PMs), and fraction metabolised (Fm), were identified as exhibiting the highest impact on the metabolism. The Bayesian meta-regression model provided good predictions for such inter-phenotypic differences. Integration of population distributions for inter-phenotypic differences and estimates for EF and Fm allowed the derivation of CYP2C9- and CYP2C19-related UFs which ranged from 2.7 to 12.7, and were above the default factor for human variability in TK (3.16) for PMs and major substrates (Fm >60%). These results provide population distributions and pathway-related UFs as conservative in silico options to integrate variability in CYP2C9 and CYP2C19 metabolism using in vitro kinetic evidence and in the absence of human data. The future development of quantitative extrapolation models is discussed with particular attention to integrating human in vitro and in vivo PK or TK data with pathway-related variability for chemical risk assessment.
MeSH term(s)	Algorithms ; Area Under Curve ; Bayes Theorem ; Computer Simulation ; Cytochrome P-450 CYP2C19/genetics ; Cytochrome P-450 CYP2C19/metabolism ; Cytochrome P-450 CYP2C9/genetics ; Cytochrome P-450 CYP2C9/metabolism ; Genetic Variation ; Humans ; Kinetics ; Phenotype ; Polymorphism, Genetic ; Risk Assessment ; Toxicokinetics ; Xenobiotics/metabolism
Chemical Substances	Xenobiotics ; CYP2C9 protein, human (EC 1.14.13.-) ; Cytochrome P-450 CYP2C9 (EC 1.14.13.-) ; CYP2C19 protein, human (EC 1.14.14.1) ; Cytochrome P-450 CYP2C19 (EC 1.14.14.1)
Language	English
Publishing date	2020-11-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2020.11.016
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Article ; Online: The Yin-Yang of CYP3A4: a Bayesian meta-analysis to quantify inhibition and induction of CYP3A4 metabolism in humans and refine uncertainty factors for mixture risk assessment.

Quignot, Nadia / Wiecek, Witold / Amzal, Billy / Dorne, Jean-Lou

Archives of toxicology

2018 Volume 93, Issue 1, Page(s) 107–119

Abstract: Quantifying differences in pharmacokinetics (PK) and toxicokinetics (TK) provides a science-based approach to refine uncertainty factors (UFs) for chemical risk assessment. Cytochrome P450 (CYP) 3A4-the major hepatic and intestinal human CYP-and the P- ... ...

Abstract	Quantifying differences in pharmacokinetics (PK) and toxicokinetics (TK) provides a science-based approach to refine uncertainty factors (UFs) for chemical risk assessment. Cytochrome P450 (CYP) 3A4-the major hepatic and intestinal human CYP-and the P-glycoprotein (Pgp) transporter share a vast range of common substrates for which PK may be modulated through inhibition or induction in the presence of grapefruit juice (GFJ) or St. John's wort (SJW), respectively. Here, an extensive literature search was performed on PK interactions for CYP3A4 and Pgp substrates after oral co-exposure to GFJ and SJW. Relevant data from 109 publications, extracted for both markers of acute (C
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B/antagonists & inhibitors ; ATP Binding Cassette Transporter, Subfamily B/metabolism ; Bayes Theorem ; Biological Availability ; Cytochrome P-450 CYP3A/metabolism ; Cytochrome P-450 CYP3A Inhibitors ; Humans ; Regression Analysis ; Risk Assessment ; Toxicokinetics ; Uncertainty
Chemical Substances	ABCB1 protein, human ; ATP Binding Cassette Transporter, Subfamily B ; Cytochrome P-450 CYP3A Inhibitors ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; CYP3A4 protein, human (EC 1.14.14.55)
Language	English
Publishing date	2018-10-08
Publishing country	Germany
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-018-2325-6
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Article ; Online: A Systematic Review of Human Challenge Trials, Designs, and Safety.

Adams-Phipps, Jupiter / Toomey, Danny / Więcek, Witold / Schmit, Virginia / Wilkinson, James / Scholl, Keller / Jamrozik, Euzebiusz / Osowicki, Joshua / Roestenberg, Meta / Manheim, David

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2022 Volume 76, Issue 4, Page(s) 609–619

Abstract: Background: Few studies have assessed participant safety in human challenge trials (HCTs). Key questions regarding HCTs include how risky such trials have been, how often adverse events (AEs) and serious adverse events (SAEs) occur, and whether risk ... ...

Abstract	Background: Few studies have assessed participant safety in human challenge trials (HCTs). Key questions regarding HCTs include how risky such trials have been, how often adverse events (AEs) and serious adverse events (SAEs) occur, and whether risk mitigation measures have been effective. Methods: A systematic search of PubMed and PubMed Central for articles reporting on results of HCTs published between 1980 and 2021 was performed and completed by 7 October 2021. Results: Of 2838 articles screened, 276 were reviewed in full. A total of 15 046 challenged participants were described in 308 studies that met inclusion criteria; 286 (92.9%) of these studies reported mitigation measures used to minimize risk to the challenge population. Among 187 studies that reported on SAEs, 0.2% of participants experienced at least 1 challenge-related SAE. Among 94 studies that graded AEs by severity, challenge-related AEs graded "severe" were reported by between 5.6% and 15.8% of participants. AE data were provided as a range to account for unclear reporting. Eighty percent of studies published after 2010 were registered in a trials database. Conclusions: HCTs are increasingly common and used for an expanding list of diseases. Although AEs occur, severe AEs and SAEs are rare. Reporting has improved over time, though not all papers provide a comprehensive report of relevant health impacts. We found very few severe symptoms or SAEs in studies that reported them, but many HCTs did not report relevant safety data. This study was preregistered on PROSPERO as CRD42021247218.
Language	English
Publishing date	2022-10-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciac820
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Article: Secukinumab's effect on structural damage progression in psoriatic arthritis: longitudinal mixture modelling of FUTURE-1 and FUTURE-5.

Luttringer, Olivier / Fox, Todd / Pricop, Luminita / Gaillez, Corine / Karcher, Helene / Wiecek, Witold / Angehrn, Zuzanna / Amzal, Billy

Clinical and experimental rheumatology

2020 Volume 39, Issue 5, Page(s) 931–937

Abstract: Objectives: Peripheral and axial manifestations of psoriatic arthritis (PsA) can lead to irreversible structural damage and chronic disability. Our objective was to explore predictors of radiographic progression and to increase our understanding of ... ...

Abstract	Objectives: Peripheral and axial manifestations of psoriatic arthritis (PsA) can lead to irreversible structural damage and chronic disability. Our objective was to explore predictors of radiographic progression and to increase our understanding of treatment effects in subgroups of patients with different rates of structural damage progression. Methods: We analysed data from two large Phase-3 trials of secukinumab in PsA patients, FUTURE-1 (NCT01392326, n=606) and FUTURE-5 (NCT02404350, n=996), where different posologies ranging from 75 mg to 300 mg were used. We applied a longitudinal Bayesian mixture model with random effects to account for the variability in the repeated radiographic assessments. "Fast progressors" were defined post hoc as patients with a 50% model-estimated probability to progress at least 0.5 mTSS/year faster than an average patient. Results: Higher baseline inflammation and higher body weight were identified as significant predictors of radiographic progression (multivariate model). Model-estimated structural damage progression in an average patient treated with secukinumab 150 mg subcutaneous (s.c.) was slower (0.04 mTSS/year; 95% CI -0.28, 0.34) compared to a patient treated with placebo (0.94 mTSS/year; 95% CI 0.45, 1.45). According to the model, the subgroup of "fast progressors" (hsCRP ≥26 mg/L, body weigth ≥94 kg, inadequate response to prior anti-TNF-alpha, structural damage ≥42 mTSS) treated with secukinumab 150 mg s.c. progressed at 0.56 mTSS/year (95% CI 0.02, 1.09) and 1.46 mTSS/year (95% CI 0.81, 2.11) when treated with placebo. Conclusions: Greater systemic inflammation and higher body weight at baseline were identified as significant predictors of progression. Even patients with fast radiographic progression could experience a beneficial effect with secukinumab that holds promise to prevent further mobility loss.
MeSH term(s)	Antibodies, Monoclonal, Humanized ; Antirheumatic Agents/adverse effects ; Arthritis, Psoriatic/diagnostic imaging ; Arthritis, Psoriatic/drug therapy ; Bayes Theorem ; Disease Progression ; Double-Blind Method ; Humans ; Treatment Outcome ; Tumor Necrosis Factor Inhibitors
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antirheumatic Agents ; Tumor Necrosis Factor Inhibitors ; secukinumab (DLG4EML025)
Language	English
Publishing date	2020-11-17
Publishing country	Italy
Document type	Journal Article
ZDB-ID	605886-3
ISSN	1593-098X ; 0392-856X
ISSN (online)	1593-098X
ISSN	0392-856X
DOI	10.55563/clinexprheumatol/ic89a8
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