Characteristics associated with poor COVID-19 outcomes in people with psoriasis, psoriatic arthritis and axial spondyloarthritis: data from the COVID-19 PsoProtect and Global Rheumatology Alliance physician-reported registries.

OBJECTIVES: To investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression. RESULTS: Of 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25-2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39-2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42-0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19. CONCLUSION: Older age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

Physiologically based pharmacokinetic modelling to inform combination dosing regimens of ceftaroline and daptomycin in special populations.

AIMS: The combination of daptomycin and ceftaroline used as salvage therapy is associated with higher survival and decreased clinical failure in complicated methicillin-resistant Staphylococcus aureus (MRSA) infections that are resistant to standard MRSA treatment. This study aimed to evaluate dosing regimens for coadministration of daptomycin and ceftaroline in special populations including paediatrics, renally impaired (RI), obese and geriatrics that generate sufficient coverage against daptomycin-resistant MRSA. METHODS: Physiologically based pharmacokinetic models were developed from pharmacokinetic studies of healthy adults, geriatric, paediatric, obese and RI patients. The predicted profiles were used to evaluate joint probability of target attainment (PTA), as well as tissue-to-plasma ratios. RESULTS: The adult dosing regimens of 6 mg/kg every (q)24h or q48h daptomycin and 300-600 mg q12h ceftaroline fosamil by RI categories achieved ≥90% joint PTA when the minimum inhibitory concentrations in the combination are at or below 1 and 4 µg/mL against MRSA. In paediatrics, wherein there is no recommended daptomycin dosing regimen for S. aureus bacteraemia, ≥90% joint PTA is achieved when the minimum inhibitory concentrations in the combination are up to 0.5 and 2 µg/mL for standard paediatric dosing regimens of 7 mg/kg q24h daptomycin and 12 mg/kg q8h ceftaroline fosamil. Model predicted tissue-to-plasma ratios of 0.3 and 0.7 in the skin and lung, respectively, for ceftaroline and 0.8 in the skin for daptomycin. CONCLUSION: Our work illustrates how physiologically based pharmacokinetic modelling can inform appropriate dosing of adult and paediatric patients and thereby enable prediction of target attainment in the patients during multitherapies.

C-H functionalization of quinoline N-oxides catalyzed by Pd(II) complexes: a computational study.

Pd(II) catalysts, particularly the acetate salt in acetic acid, tended to favor regioselective C-H activation of quinoline N-oxides (QOs) at the C2 position. However, Pd(II)Cl2 was shown to catalyze their C-H activation at C8 and, in the presence of water, C8-H activation was accompanied by the formation of 2-quinolinones. The aim of the DFT study described in this work was to shed light on the complete mechanism of these competing catalytic reactions, when PdCl2 reacts with QO and benzaldehyde in dichloroethane. C-H activation of QO was the first step of the reaction and involved either a metallacycle, with a CQO-Pd(II) σ-bond and a C(8)-H-Pd(II) agostic bond, or an η3-QO complex, with three carbon atoms of the heteroring of QO binding PdCl2. The first situation led to the unusual C8 activation and the second to C2 activation. The σ-metallacycle undergoes C8-H activation and the energy of the TOF determining the transition state to form the product is ∼17 kcal mol-1, while for the reaction through the π-metallacycle (C2-H activation) the corresponding energy is higher (∼29 kcal mol-1) and thus is not competitive under the same conditions. The reaction proceeding through the σ-complex, activating the C8 position, is preferred, in agreement with experimental results. Both reactions involve oxidation of Pd(II) to Pd(IV) and the catalyst is regenerated. When small amounts of water are added to the reaction mixture, C8-H activation (acylation) results from the same σ-metallacycle with the same barrier, but the simultaneous formation of 2-quinolinones is more complicated. It starts with OH- attack at the C2 position, and is followed by the migration of two hydrogen atoms, and the final reductive elimination step ends with Pd(0). The higher barriers for the migration and reoxidation of Pd(0) are associated with the more demanding reaction conditions. The different reactivity of Pd(II)(OAc)2 under analogous conditions is clarified, as it is only capable of forming the above mentioned π-complex and thus of activating the C2 position of QO. This catalyst can preferentially activate the C8-H bond under rather different conditions, including in particular acetic acid medium, as shown by other authors.

Integration of artificial neural network and physiologically based biopharmaceutic models in the development of sustained-release formulations.

Model-informed drug development is an important area recognized by regulatory authorities and is gaining increasing interest from the generic drug industry. Physiologically based biopharmaceutics modeling (PBBM) is a valuable tool to support drug development and bioequivalence assessments. This study aimed to utilize an artificial neural network (ANN) with a multilayer perceptron (MLP) model to develop a sustained-release matrix tablet of metformin HCl 500 mg, and to test the likelihood of the prototype formulation being bioequivalent to Glucophage® XR, using PBBM modeling and virtual bioequivalence (vBE). The ANN with MLP model was used to simultaneously optimize 735 formulations to determine the optimal formulation for Glucophage® XR release. The optimized formulation was evaluated and compared to Glucophage® XR using PBBM modeling and vBE. The optimized formulation consisted of 228 mg of hydroxypropyl methylcellulose (HPMC) and 151 mg of PVP, and exhibited an observed release rate of 42% at 1 h, 47% at 2 h, 55% at 4 h, and 58% at 8 h. The PBBM modeling was effective in assessing the bioequivalence of two formulations of metformin, and the vBE evaluation demonstrated the utility and relevance of translational modeling for bioequivalence assessments. The study demonstrated the effectiveness of using PBBM modeling and model-informed drug development methodologies, such as ANN and MLP, to optimize drug formulations and evaluate bioequivalence. These tools can be utilized by the generic drug industry to support drug development and biopharmaceutics assessments.

A singlet-triplet hole spin qubit in planar Ge.

Spin qubits are considered to be among the most promising candidates for building a quantum processor. Group IV hole spin qubits are particularly interesting owing to their ease of operation and compatibility with Si technology. In addition, Ge offers the option for monolithic superconductor-semiconductor integration. Here, we demonstrate a hole spin qubit operating at fields below 10 mT, the critical field of Al, by exploiting the large out-of-plane hole g-factors in planar Ge and by encoding the qubit into the singlet-triplet states of a double quantum dot. We observe electrically controlled g-factor difference-driven and exchange-driven rotations with tunable frequencies exceeding 100 MHz and dephasing times of 1 µs, which we extend beyond 150 µs using echo techniques. These results demonstrate that Ge hole singlet-triplet qubits are competing with state-of-the-art GaAs and Si singlet-triplet qubits. In addition, their rotation frequencies and coherence are comparable with those of Ge single spin qubits, but singlet-triplet qubits can be operated at much lower fields, emphasizing their potential for on-chip integration with superconducting technologies.

Dynamics of Hole Singlet-Triplet Qubits with Large g-Factor Differences.

The spin-orbit interaction permits to control the state of a spin qubit via electric fields. For holes it is particularly strong, allowing for fast all electrical qubit manipulation, and yet an in-depth understanding of this interaction in hole systems is missing. Here we investigate, experimentally and theoretically, the effect of the cubic Rashba spin-orbit interaction on the mixing of the spin states by studying singlet-triplet oscillations in a planar Ge hole double quantum dot. Landau-Zener sweeps at different magnetic field directions allow us to disentangle the effects of the spin-orbit induced spin-flip term from those caused by strongly site-dependent and anisotropic quantum dot g tensors. Our work, therefore, provides new insights into the hole spin-orbit interaction, necessary for optimizing future qubit experiments.

Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach.

AIMS: The aim of this work is the development of a mechanistic physiologically-based pharmacokinetic (PBPK) model using in vitro to in vivo extrapolation to conduct a drug-drug interaction (DDI) assessment of treosulfan against two cytochrome p450 (CYP) isoenzymes and P-glycoprotein (P-gp) substrates. METHODS: A PBPK model for treosulfan was developed de novo based on literature and unpublished clinical data. The PBPK DDI analysis was conducted using the U.S. Food and Drug Administration (FDA) DDI index drugs (probe substrates) midazolam, omeprazole and digoxin for CYP3A4, CYP2C19 and P-gp, respectively. Qualified and documented PBPK models of the probe substrates have been adopted from an open-source online model database. RESULTS: The PBPK model for treosulfan, based on both in vitro and in vivo data, was able to predict the plasma concentration-time profiles and exposure levels of treosulfan applied for a standard conditioning treatment. Medium and low potentials for DDI on CYP3A4 (maximum area under the concentration-time curve ratio (AUCRmax = 2.23) and CYP2C19 (AUCRmax = 1.6) were predicted, respectively, using probe substrates midazolam and omeprazole. Treosulfan was not predicted to cause a DDI on P-gp. CONCLUSION: Medicinal products with a narrow therapeutic index (eg, digoxin) that are substrates for CYP3A4, CYP2C19 or P-gp should not be given during treatment with treosulfan. However, considering the comprehensive treosulfan-based conditioning treatment schedule and the respective pharmacokinetic properties of the concomitantly used drugs (eg, half-life), the potential for interaction on all evaluated mechanisms would be low (AUCR < 1.25), if concomitantly administered drugs are dosed either 2 hours before or 8 hours after the 2-hour intravenous infusion of treosulfan.

Aztreonam/avibactam effect on pharmacodynamic indices for mutant selection of Escherichia coli and Klebsiella pneumoniae harbouring serine- and New Delhi metallo-ß-lactamases.

OBJECTIVES: Ceftazidime/avibactam is not active against MBL-producing bacteria. Combining ceftazidime/avibactam or avibactam with aztreonam can counter the resistance of MBL-producing Enterobacterales. The aim of this study was to evaluate whether the addition of avibactam could reduce or close the mutant selection window (MSW) of aztreonam in Escherichia coli and Klebsiella pneumoniae harbouring MBLs; MSW is a pharmacodynamic (PD) parameter for the selection of emergent resistant mutants. METHODS: In vitro susceptibility of 19 clinical isolates to ceftazidime/avibactam, aztreonam alone, and in co-administration (aztreonam/ceftazidime/avibactam and aztreonam/avibactam) was determined, as well as the mutant prevention concentration (MPC). The fraction of time within 24 h that the free drug concentration was within the MSW (fTMSW) and the fraction of time that the free drug concentration was above the MPC (fT>MPC) in both plasma and epithelial lining fluid (ELF) were determined from simulations of 10 000 profiles. The joint PTA was used to derive a joint cumulative fraction of response (CFR). RESULTS: All isolates were resistant to ceftazidime/avibactam or aztreonam. Combining aztreonam and avibactam or ceftazidime/avibactam resulted in synergistic bactericidal activities against all isolates. Synergism was primarily due to the aztreonam/avibactam combination. For aztreonam/avibactam dosing regimens evaluated in clinical trials, fT>MPC values were >90% and >80%, whereas fTMSW measures were <10% and <20% in plasma and ELF, respectively. The CFR was 100% for aztreonam/avibactam against the collection of clinical isolates. CONCLUSIONS: Effective antimicrobial combination optimized the PD parameters measuring selection for emergent mutants by increasing fT>MPC and reducing fTMSW.

Probing the Catalytically Active Species in POM-Catalysed DNA-Model Hydrolysis*.

Phosphoester hydrolysis is an important chemical step in DNA repair. One archetypal molecular model of phosphoesters is para-nitrophenylphosphate (pNPP). It has been shown previously that the presence of molecular metal oxide [Mo7 O24 ]6- may catalyse the hydrolysis of pNPP through the partial decomposition of polyoxomolybdate framework resulting in a [(PO4 )2 Mo5 O15 ]6- product. Real-time monitoring of the catalytic system using electrospray ionisation mass spectrometry (ESI-MS) provided a glance into the species present in the reaction mixture and identification of potential catalytic candidates. Following up on the obtained spectrometric data, Density Functional Theory (DFT) calculations were carried out to characterise the hypothetical intermediate [Mo5 O15 (pNPP)2 (H2 O)6 ]6- that would be required to form under the hypothesised transformation. Surprisingly, our results point to the dimeric [Mo2 O8 ]4- anion resulting from the decomposition of [Mo7 O24 ]6- as the active catalytic species involved in the hydrolysis of pNPP rather than the originally assumed {Mo5 O15 } species. A similar study was carried out involving the same species but substituting Mo by W. The mechanism involving W species showed a higher barrier and less stable products in agreement with the non-catalytic effect found in experimental results.

Physiologically based pharmacokinetic-pharmacodynamic evaluation of meropenem plus fosfomycin in paediatrics.

AIMS: The objective of the current study was to evaluate paediatric dosing regimens for meropenem plus fosfomycin that generate sufficient coverage against multidrug-resistant bacteria. METHODS: The physiologically based pharmacokinetic (PBPK) models of meropenem and fosfomycin were developed from previously published pharmacokinetic studies in five populations: healthy subjects of Japanese origin, and healthy adults, geriatric, paediatric and renally impaired of primarily Caucasian origins. Pharmacodynamic (PD) analyses were carried out by evaluating dosing regimens that achieved a ≥90% joint probability of target attainment (PTA), which was defined as the minimum of the marginal probabilities to achieve the target PD index of each antibiotic. For meropenem, the percentage of time over a 24-hour period wherein the free drug concentration was above the minimum inhibitory concentration (fT > MIC) of at least 40% was its PD target. The fosfomycin PD index was described by fAUC/MIC of at least 40.8. RESULTS: For coadministration consisting of 20 mg/kg meropenem q8h as a 3-hour infusion and 35 mg/kg fosfomycin q8h also as a 3-hour infusion in a virtual paediatric population between 1 month and 12 years of age with normal renal function and a corresponding body weight between 3 and 50 kg, a joint PTA ≥ 90% is achieved at MICs of 16 and 64 mg/L for meropenem and fosfomycin coadministration, respectively, against Klebsiella pneumoniae and Pseudomonas aeruginosa. CONCLUSION: The current study identified potentially effective paediatric dosing regimens for meropenem plus fosfomycin coadministration against multidrug-resistant bacteria.

New Insights on the Interaction of Phenanthroline Based Ligands and Metal Complexes and Polyoxometalates with Duplex DNA and G-Quadruplexes.

This work provides new insights from our team regarding advances in targeting canonical and non-canonical nucleic acid structures. This modality of medical treatment is used as a form of molecular medicine specifically against the growth of cancer cells. Nevertheless, because of increasing concerns about bacterial antibiotic resistance, this medical strategy is also being explored in this field. Up to three strategies for the use of DNA as target have been studied in our research lines during the last few years: (1) the intercalation of phenanthroline derivatives with duplex DNA; (2) the interaction of metal complexes containing phenanthroline with G-quadruplexes; and (3) the activity of Mo polyoxometalates and other Mo-oxo species as artificial phosphoesterases to catalyze the hydrolysis of phosphoester bonds in DNA. We demonstrate some promising computational results concerning the favorable interaction of these small molecules with DNA that could correspond to cytotoxic effects against tumoral cells and microorganisms. Therefore, our results open the door for the pharmaceutical and medical applications of the compounds we propose.

A comprehensive molecular phylogeny of Afrotropical white-eyes (Aves: Zosteropidae) highlights prior underestimation of mainland diversity and complex colonisation history.

White-eyes (Zosterops) are a hyper-diverse genus of passerine birds that have rapidly radiated across the Afrotropics and Southeast Asia. Despite their broad range, a disproportionately large number of species are currently recognised from islands compared to the mainland. Described species-level diversity of this 'great speciator' from continental Africa-Arabia is strikingly low, despite the vast size and environmental complexity of this region. However, efforts to identify natural groups using traditional approaches have been hindered by the remarkably uniform morphology and plumage of these birds. Here, we investigated the phylogenetic relationships and systematics of Afrotropical Zosterops, including the Gulf of Guinea and western Indian Ocean islands. We included exceptional sampling (~160 individuals) from all except one subspecies of the 55 taxa (32 species, plus 23 additional named sub-species) currently recognized throughout the region, in addition to a subset of extra-Afrotropical taxa, by exploiting blood and archival samples. Employing a multi-locus phylogenetic approach and applying quantitative species delimitation we tested: (1) if there has been a single colonisation event of the Afrotropical realm; (2) if constituent mainland and island birds are monophyletic; and (3) if mainland diversity has been underestimated. Our comprehensive regional phylogeny revealed a single recent colonisation of the Afrotropical realm c.1.30 Ma from Asia, but a subsequent complex colonisation history between constituent island and mainland lineages during their radiation across this vast area. Our findings suggest a significant previous underestimation of continental species diversity and, based on this, we propose a revised taxonomy. Our study highlights the need to densely sample species diversity across ranges, providing key findings for future conservation assessments and establishing a robust framework for evolutionary studies.

Pharmacokinetics, Pharmacodynamics and Dermal Distribution of 5-Methoxypsoralen Based on a Physiologically Based Pharmacokinetic Model to Support Phytotherapy Using Brosimum gaudichaudii.

The treatment of vitiligo includes the combination of psoralens and ultraviolet type A exposure. Psoralens belong to a group of natural furanocoumarins that cause the skin to become sensitive temporarily to ultraviolet type A. The aim of this study was to develop a physiologically based pharmacokinetic model of 5-MOP from Brosimum gaudichaudii to support psoralen and ultraviolet type A therapy. A study of rats was used to establish and validate rat tissue distribution. The same chemical-specific parameters used in the rat model were also employed in the human model to project human pharmacokinetics. The highest exposures in the rats were in the brain and skin. Following a single dose of 1.2 mg/kg 5-MOP in humans, the model predicted a maximum concentration of 20 ng/mL and an area under the curve of 125 ng.h/mL, matching clinical results. The half-maximum melanogenesis concentrations in B16F10 cells were 29.5, 18.5, 11.5, and 6.5 ng/mL for synthetic 5-MOP, synthetic 5-MOP with ultraviolet type A, B. gaudichaudii alone, and B. gaudichaudii plus ultraviolet type A, respectively. Physiologically based pharmacokinetic model prediction in humans supported a once-every-two-day regimen for optimal melanin production. This type of framework can be applied to support strategies for dose selection and to investigate the impact of drugs on melanocyte recovery.

Physiologically-based pharmacokinetics of ziprasidone in pregnant women.

AIMS: Pregnancy is associated with physiological changes that alter the pharmacokinetics (PK) of drugs. The aim of this study was to predict the PK of ziprasidone in pregnant women. METHODS: A full physiologically-based pharmacokinetic (PBPK) model of ziprasidone was developed and validated for the non-pregnant population (healthy adults, paediatrics, geriatrics), and this was extended to the pregnant state to assess the change in PK profile of ziprasidone throughout pregnancy. RESULTS: The PBPK model successfully predicted the ziprasidone disposition in healthy adult volunteers, wherein the predicted and observed AUC, Cmax and tmax were within the fold-difference of 0.94-1.09, 0.89-1.40 and 0.80-1.08, respectively. The paediatric and geriatric population, also showed predicted AUC, Cmax and tmax within a two-fold range of the observed values. The simulated exposure in pregnant women using a p-PBPK model showed no significant difference when compared to non-pregnant women. CONCLUSIONS: The PBPK model predicted the impact of physiological changes during pregnancy on PK and exposure of ziprasidone, suggesting that dose adjustment is not necessary in this special population.

Spectrum of the Nuclear Environment for GaAs Spin Qubits.

Using a singlet-triplet spin qubit as a sensitive spectrometer of the GaAs nuclear spin bath, we demonstrate that the spectrum of Overhauser noise agrees with a classical spin diffusion model over 6 orders of magnitude in frequency, from 1 mHz to 1 kHz, is flat below 10 mHz, and falls as 1/f^{2} for frequency f≳1 Hz. Increasing the applied magnetic field from 0.1 to 0.75 T suppresses electron-mediated spin diffusion, which decreases the spectral content in the 1/f^{2} region and lowers the saturation frequency, each by an order of magnitude, consistent with a numerical model. Spectral content at megahertz frequencies is accessed using dynamical decoupling, which shows a crossover from the few-pulse regime (≲16π pulses), where transverse Overhauser fluctuations dominate dephasing, to the many-pulse regime (≳32 π pulses), where longitudinal Overhauser fluctuations with a 1/f spectrum dominate.

Negative Spin Exchange in a Multielectron Quantum Dot.

We use a one-electron quantum dot as a spectroscopic probe to study the spin properties of a gate-controlled multielectron GaAs quantum dot at the transition between odd and even occupation numbers. We observe that the multielectron ground-state transitions from spin-1/2-like to singletlike to tripletlike as we increase the detuning towards the next higher charge state. The sign reversal in the inferred exchange energy persists at zero magnetic field, and the exchange strength is tunable by gate voltages and in-plane magnetic fields. Complementing spin leakage spectroscopy data, the inspection of coherent multielectron spin exchange oscillations provides further evidence for the sign reversal and, inferentially, for the importance of nontrivial multielectron spin exchange correlations.

Noise Suppression Using Symmetric Exchange Gates in Spin Qubits.

We demonstrate a substantial improvement in the spin-exchange gate using symmetric control instead of conventional detuning in GaAs spin qubits, up to a factor of six increase in the quality factor of the gate. For symmetric operation, nanosecond voltage pulses are applied to the barrier that controls the interdot potential between quantum dots, modulating the exchange interaction while maintaining symmetry between the dots. Excellent agreement is found with a model that separately includes electrical and nuclear noise sources for both detuning and symmetric gating schemes. Unlike exchange control via detuning, the decoherence of symmetric exchange rotations is dominated by rotation-axis fluctuations due to nuclear field noise rather than direct exchange noise.

Advancing Virtual Bioequivalence for Orally Administered Drug Products: Methodology, Real-World Applications and Future Outlook.

Bioequivalence studies are pivotal in generic drug development wherein therapeutic equivalence is provided with an innovator product. However, bioequivalence studies represent significant complexities due to the interplay of multiple factors related to drug, formulation, physiology, and pharmacokinetics. Approaches such as physiologically based biopharmaceutics modeling (PBBM) can enable virtual bioequivalence (VBE) assessment through appropriately developed and validated models. Such models are now being extensively used for bioequivalence risk assessment, internal decision-making, and the evaluation of drug and formulation factors related to bioequivalence. Depiction of the above-mentioned factors through the incorporation of variability and development of a virtual population for bioequivalence assessment is of paramount importance in utilizing such models. In this manuscript, we have portrayed our current understanding of VBE. A detailed explanation was provided with respect to study designs, in vivo variability, and the impact of physiological, drug, and formulation factors on the development of the population for VBE. Furthermore, strategies are suggested to incorporate variability in GastroPlus with an emphasis on intra-subject and inter-occasion variability. Two industrial case studies pertaining to immediate and modified release formulation were portrayed wherein VBE was utilized for decision-making and regulatory justification. Finally, regulatory understanding in the area of VBE, along with future perspectives, was detailed.

Neutrophile to lymphocyte and platelet to lymphocyte ratios predict clinical response to bDMARD in naïve spondylarthritis patients.

Objective: We aim to study association between neutrophile to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios and disease activity, and their value to predict bDMARD response. Methods: A set of spondylarthritis (SpA) patients under bDMARD registered in the Reuma.pt registry was studied. Sociodemographic, clinical and laboratorial variables were assessed on bDMARD initiation, 6, 12, 18 and 24 months (M) thereafter. Univariable and multivariable generalized estimation equations models assessed associations with disease activity. The NLR and PLR predictive value was assessed using univariable and multivariable logistic regression models. Results: A total of 170 patients were included. Most were male (54.7%), with a predominantly axial phenotype (84.7%). Significant associations were observed between NLR [B=1.55, 95% confidence interval (CI) = (1.38; 1.74)] and PLR [(B=1.16, 95% CI = (1.09; 1.24)] with ASDAS-CRP (p < 0.001). Both baseline ratios predicted ∆ ASDAS-CRP ≥ 1.1 at 6 months [OR = 2.20, 95% CI = (1.21, 4.00) for NLR; OR = 1.02, 95% CI = (1.01, 1.04) for PLR, p < 0.01)]. PLR was a significant predictor of ∆ ASDAS-CRP ≥ 1.1 in all timepoints [OR (12 M) = 1.02, 95% CI = (1.00, 1.03), p < 0.05; OR (18M) = 1.02, 95% CI = (1.01, 1.03), p < 0.001; OR (24M) = 1.01, 95% CI = (1.01, 1.02), p < 0.01]. Conclusion: NLR and PLR were associated with disease activity during the follow up of these patients. They seem to be significant predictors of therapeutic response to bDMARD in naïve SpA patients.