Early monitoring of anti-infliximab antibodies by drug-tolerant assay predicts later immunogenicity and drug survival in rheumatic diseases.

OBJECTIVES: To investigate the appearance of anti-drug antibodies (ADA) against infliximab (IFX) determined by drug-sensitive and drug-tolerant assays and their relationship with drug levels and drug survival. METHODS: This longitudinal observational study included 45 patients with rheumatoid arthritis (RA) and 61 with spondyloarthritis (SpA). Serum samples were obtained at weeks 2, 6, 12, 24, and 52. Serum IFX levels were measured by a capture enzyme-linked immunosorbent assay (ELISA) and ADA by an in-house drug-sensitive two-site (bridging) enzyme-linked immunosorbent assay (bELISA) and a commercially available drug-tolerant ELISA (IDK, Immundiagnostik, Germany). RESULTS: Anti-drug antibodies were detected earlier by IDK than by bELISA. Once ADA appeared, positivity persisted throughout the study period. Patients who were bELISA ADA+ had higher IDK ADA levels (than bELISA ADA- patients). Circulating IFX levels were detected in all patients except those found to be bELISA ADA+. Serum IFX levels were lower in IDK ADA+ than in IDK ADA-patients.Most patients (64%) discontinued due to inefficacy. The early onset of immunogenicity was related to IFX survival. Both in RA and SpA, the median survival (years) was shorter in patients with earlier development of ADA (IDK+ before or at week 24) than those who became IDK+ later (after week 24) or never developed ADA. CONCLUSION: A drug-tolerant assay detects ADA during IFX therapy earlier and more frequently than a drug-sensitive assay. The onset of immunogenicity detected by drug-tolerant assays is related to the subsequent detection of ADA by drug-sensitive assays and drug survival.

Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica.

OBJECTIVE: The aim of the present study was to determine the clinical significance of subclinical giant cell arteritis (GCA) in polymyalgia rheumatica (PMR) and ascertain its optimal treatment approach. METHODS: Patients with PMR who fulfilled the 2012 European Alliance of Associations for Rheumatology/American College of Rheumatology Provisional Classification Criteria for PMR, did not have GCA symptoms and were routinely followed up for 2 years and were stratified into two groups, according to their ultrasound results: isolated PMR and PMR with subclinical GCA. The outcomes (relapses, glucocorticoid use and disease-modifying antirheumatic drug treatments) between groups were compared. RESULTS: We included 150 patients with PMR (50 with subclinical GCA) with a median (IQR) follow-up of 22 (20-24) months. Overall, 47 patients (31.3 %) had a relapse, 31 (62%) in the subclinical GCA group and 16 (16%) in the isolated PMR group (p<0.001). Among patients with subclinical GCA, no differences were found in the mean (SD) prednisone starting dosage between relapsed and non-relapsed patients (32.4±15.6 vs 35.5±12.1 mg, respectively, p=0.722). Patients with subclinical GCA who relapsed had a faster prednisone dose tapering in the first 3 months compared with the non-relapsed patients, with a mean dose at the third month of 10.0±5.2 versus 15.2±7.9 mg daily (p<0.001). No differences were found between relapsing and non-relapsed patients with subclinical GCA regarding age, sex, C reactive protein and erythrocyte sedimentation rate. CONCLUSIONS: Patients with PMR and subclinical GCA had a significantly higher number of relapses during a 2-year follow-up than patients with isolated PMR. Lower starting doses and rapid glucocorticoid tapering in the first 3 months emerged as risk factors for relapse.

Patient and physician assessment in difficult-to-treat rheumatoid arthritis: patterns of subjective perception at early stages of b/tsDMARD treatment.

OBJECTIVES: To analyse the trajectories of Disease Activity Score 28 (DAS28), patient global assessment (PGA) and physician global assessment (PhGA) and to assess their predictive capabilities on difficult-to-treat rheumatoid arthritis (D2TRA) classification. METHODS: Longitudinal study of patients with rheumatoid arthritis (RA) from 2020 to 2022. Based on the D2TRA EULAR (European Alliance of Associations for Rheumatology) definition, patients were classified as D2TRA according to biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) failure due to inefficacy (D2TRA-inefficacy) or other reasons (D2TRA-other). Patients who did not fulfil the D2TRA criteria were classified as NoD2TRA. DAS28, PGA and PhGA scores collected every 6 months during the first 24 months of b/tsDMARD treatment were used to identify different trajectories using latent class mixed models (LCMM). RESULTS: The study population comprised 255 patients with RA, of whom 167 were NoD2TRA, 58 D2TRA-inefficacy and 30 D2TRA-other. LCMM stratified patients into two different trajectories for DAS28 and PhGA and three for PGA according to the most stable model. The most notable variation occurred during the first 6 months of treatment, thereafter remaining stable during the follow-up period. Most D2TRA-inefficacy patients fitted the trajectory, showing higher values of the studied parameters. NoD2TRA followed the trajectory with lower values, and D2TRA-other were distributed more homogeneously across all trajectories. CONCLUSIONS: The assessment of disease activity, together with patients' and physicians' perceptions, form a key element in the correct discrimination of patients who are going to develop D2TRA-inefficacy. However, identifying those patients who will be D2TRA-other remains challenging, whether by subjective or objective parameters.

Immune response after SARS-CoV-2 vaccination in patients with inflammatory immune-mediated diseases receiving immunosuppressive treatment.

BACKGROUND: Real world data on the response to the SARS-CoV-2 vaccine in patients with immunomediated diseases (IMIDs) treated with immunesuppressants is of great interest because vaccine response may be impaired. The main aim was to study the humoral and cellular immune response after SARS-CoV-2 vaccination in patients with IMIDs treated with immunosuppressants. The secondary aim was to describe the frequency of SARS-CoV-2 infections after vaccination in these patients. MATERIAL AND METHODS: This is an observational study including 86 patients with IMIDs. All patients were treated with biologic or targeted synthetic disease-modifying antirheumatic drugs [b/tsDMARDs: TNF inhibitors (TNFi), rituximab, anti-interleukin 6 receptor (anti-IL6R) or JAK inhibitors (JAKi)]. Demographic and clinical information were collected. After 4-6 weeks of 2nd and 3rd vaccine doses, humoral response was assessed using the Thermo Scientific ELiA SARS-CoV-2-Sp1 IgG Test. Also, in patients with serum SARS-CoV-2 antibody levels under 100UI/ml, cellular response was analyzed using the QuantiFERON SARS-CoV-2 Starter Pack. RESULTS: A total of 86 patients under b/tsDMARDs and 38 healthy controls were included. Most patients received TNFi (45 with TNFi, 31 with rituximab, 5 with anti-IL6R and 5 with JAKi). SARS-CoV-2 antibodies (Ab) were present in an 86% of patients with IMIDs and in 100% healthy controls (p = 0.017). However, 12 (14%) patients had undetectable SARS-CoV-2 Ab levels, all treated with rituximab. In addition, SARS-CoV-2 Ab (IU/ml) were statistically lower in patients (Mdn (IQR): 59.5 (17-163) in patients vs 625 (405-932) in controls, p < 0.001). Patients treated with rituximab had lower Ab levels than those treated with TNFi and controls (p < 0.001). The cellular response to SARS-CoV-2 vaccine was evaluated in 30 patients. Eleven patients had a positive cellular response, being more frequent in patients treated with rituximab (p = 0.03). SARS-CoV-2 infection was reported in 43% of patients and 34% of controls after vaccination. Only 6 (7%) patients required hospitalization, most of whom treated with rituximab (67%). CONCLUSION: SARS-CoV-2 antibody levels were lower in patients than in controls, especially in patients treated with rituximab. A cellular response can be detected despite having a poor humoral response. Severe infections in vaccinated patients with IMIDs are rare, and are observed mainly in patients treated with rituximab.

Performance of the 2022 ACR/EULAR giant cell arteritis classification criteria for diagnosis in patients with suspected giant cell arteritis in routine clinical care.

OBJECTIVE: To examine the performance of the new 2022 American College of Rheumatology (ACR)/EULAR giant cell arteritis (GCA) classification criteria for diagnosis in routine clinical care. METHODS: Multicentric retrospective observational study of patients referred to two ultrasound (US) fast track clinics. Patients with GCA were compared with unselected controls with suspected GCA. The gold standard for GCA diagnosis has been clinical confirmation after 6 months of follow-up. All patients underwent an US exam of temporal and extracranial arteries (carotid, subclavian and axillary) at baseline. Fluorodeoxyglucose-positron emission tomography/CT was performed according to standard clinician criteria. The performance of the new 2022 ACR/EULAR GCA classification criteria was evaluated in all patients with GCA across different subsets of the disease. RESULTS: A total of 319 patients (188 cases, 131 controls) were included for analysis (mean age 76 years, 58.9% females). Overall, the 2022 EULAR/ACR GCA classification criteria had a sensitivity of 92.6% and a specificity of 71.8%, using GCA clinical diagnosis as external criterion and the area under the curve (AUC) was 0.928 (95% CI 0.899 to 0.957). Isolated large vessel-GCA showed a sensitivity of 62.2% and a specificity of 71.8% (AUC 0.691 (0.592 to 0.790)), while biopsy-proven GCA showed a sensitivity of 100% and a specificity of 71.8% (AUC 0.989 (0.976 to 1)). Overall sensitivity and specificity of the 1990 ACR criteria was 53.2% and 80.2%, respectively. CONCLUSIONS: The new 2022 ACR/EULAR GCA classification criteria showed adequate diagnostic accuracy in patients with suspected GCA under routine care, and an improvement on the sensitivity and specificity of the 1990 ACR classification criteria in all patient subsets.

A paradigm of difficult-to-treat rheumatoid arthritis: subtypes and early identification.

OBJECTIVES: Multiple failures to biologic or targeted specific disease-modifying anti-rheumatic drugs (b/tsDMARDs) that lead to difficult-to-treat rheumatoid arthritis (D2TRA) may be the result of multi-drug inefficacy or reflect treatment problems related to adverse events, comorbidities, and/or poor adherence. We aimed to characterise a cohort of D2TRA patients in clinical practice, to analyse the differences between D2TRA due to inefficacy versus D2TRA from other causes, and to compare them with non-D2TRA. METHODS: The D2TRA group included patients who were receiving ≥2b/tsDMARDs due to inefficacy (D2TRA-inef cacy) or because of adverse events, poor adherence, contraindications, comorbidities, drug-intolerance, etc. (D2TRA-other). Patients who achieved low disease activity or remission with the rst bDMARD were classified as non-D2TRA patients. For all patients, demographic, clinical characteristics and laboratory parameters were assessed prior to starting the rst b/tsDMARD. Descriptive analysis was performed and bivariate logistic regression models were assembled. RESULTS: In total, 253 patients were included: 131 non-D2TRA and 122 D2TRA [86 (70.5%) D2TRA-inefficacy and 36 (29.5%) D2TRA-other]. Comparison of the two groups of D2TRA patients: no differences in gender, age at start of b/tsDMARD or age at RA diagnosis were found; this was also true of socioeconomic status, frequency of anxiety-depression and other comorbidities. Patients categorised as D2TRA-other had less extra-articular manifestations than D2TRA-inef cacy, as well as lower values of DAS28 at the start of the rst b/tsDMARD. Comparisons of Non-D2TRA patients versus D2TRA-other resulted in the following observations: no differences in sociodemographic characteristics were evident nor were there any differences in terms of disease activity. CONCLUSIONS: Patients with D2TRA-other are indistinguishable from non-D2TRA patients at baseline, indicating the former cohort does not appear to have any predictive value during the early stages of b/tsDMARD treatment, unlike what occurs in patients with D2TRA-inefficacy.

Achievement rate and predictive factors of the recommended therapeutical target in patients with axial spondyloarthritis who remain on biological therapy: a prospective cohort study in Spain.

OBJECTIVES: To determine the frequency of sustained remission (R) or low diseas activity (LDA) in patients with axial spondyloarthritis (axSpA) undergoing long-term biological therapy and to analyse predictive factors for achieving these outcomes. DESIGN: Prospective, observational cohort study. SETTING: Spanish hospital. PARTICIPANTS: Patients with axSpA who initiated biological treatment between 2003 and 2017. INTERVENTION: Assessment of demographic and clinical characteristics at the beginning of treatment and disease activity every 6 months up to a maximum of 2 years. MAIN OUTCOME MEASURES: Disease activity was measured by Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index and C reactive protein (BASDAI&CRP). Sustained R was defined as ASDAS<1.3 and/or BASDAI <2 and normal CRP while sustained LDA was defined as ASDAS <2.1 and/or BASDAI <4 and normal CRP on at least three consecutive visits. RESULTS: In total 186 patients (66.1% men and 75.3% with radiographic sacroiliitis) were included. Overall, 76.8% of patients achieved ASDAS R/LDA (R53.2%/LDA23.6%) in at least one visit. Forty per cent (R17.6%/LDA22.4%) of the patients fulfilled the sustained ASDAS R/LDA state, whereas only 30.8% maintained this status (R14.8%/LDA15.9%) according to BASDAI&CRP. In the multivariate analysis, male sex (OR=4.01), younger age at the beginning of biological therapy (OR=0.96) and an HLA*B27 positive status (OR=4.30) were associated with achieving sustained ASDAS R/LDA. CONCLUSIONS: In clinical practice, around one-third of patients on biological disease-modifying antirheumatic drugs achieve a sustained R/LDA status, but these rates drop to less than one in five when targeting remission, preventing the use of the latter as a feasible target. Male sex, HLA*B27 positivity and younger age at the beginning of biological therapy are the main predictors for achieving sustained R/LDA.

Validity of the EULAR recommendations on the use of ultrasound in the diagnosis of giant cell arteritis.

OBJECTIVES: The European Alliance of Associations for Rheumatology (EULAR) recommendations for the use of imaging in large vessel vasculitis establish that an imaging test supported by clinical pretest probability (PTP) is sufficient for the diagnosis of giant cell arteritis (GCA). Our objective was to determine the validity of the EULAR recommendations on the use of Colour duplex ultrasound (CDUS) in GCA after calculating the PTP. METHODS: We collected data of all patients referred to our fast-track clinic between 2016 and 2020. The Southend pretest probability score (SPTPS) was calculated and classified as low (LR), intermediate and high risk (HR) according to the values obtained by its authors, <9, 9-12 and >12, respectively. All patients underwent a CDUS of the temporal arteries with their common, parietal and frontal branches, and the most also axillary (86.5%), and subclavian and carotid arteries. The gold-standard diagnosis was made according to the physician's criteria after at least 9 months of follow-up. RESULTS: Of the 297 referred patients, 97 (32.7%) were diagnosed with GCA. The SPTPS area under the ROC curve was 0.787. The LR category included 105 patients (35.4%), of which 10 (9.5%) had GCA and 1 had a CDUS false negative result. The HR category included 67 patients (22.5%), 47 with GCA, and in 1 case the CDUS result was a false positive. CONCLUSION: Combining the results of a PTP score, such as SPTPS, and the CDUS allows for an accurate diagnosis of GCA, as established by the EULAR group, with less than 2% misclassification of diagnosis.

Obesity and response to biological therapy in rheumatoid arthritis: the role of body mass index and adipose tissue cytokines.

OBJECTIVES: To analyse the role of body mass index (BMI) in the clinical response to biologic dis-ease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). To per-form an in-depth analysis of the pathophysiology of obesity by assessing serum adipokine levels and their potential changes according to treatment. METHODS: This study involved 105 patients with RA starting tumour necrosis factor inhibitors (TNFi) or tocilizumab (TCZ). Patients were classified ac-cording to BMI as normal-weight and overweight/obesity. The clinical response to treatment was as-sessed by Clinical Disease Activity Index (CDAI) 6 months after initiation of bDMARDs. Serum adi-pokines (leptin and adiponectin) were determined using a commercial immunoassay kit in samples ob-tained before initiation of bDMARDs and after 6 months of treatment. RESULTS: A correlation was observed between BMI and disease activity and between BMI and serum adipokines. Sixty percent of patients achieved low disease activity (LDA)/remission: 45 patients in TNFi group (64.2%) and 18 (51.4%) in TCZ group. In TNFi group, patients who did not attain LDA/remission had a higher BMI (kg/m2) ([28.7±5.1] vs. [24.5±4.6], p=0.001) and baseline CDAI (26.3 [17.4-33.9] vs. 19.8 [14.0-28.8], p<0.03). However, no differences in BMI or baseline CDAI were observed between patients who achieved LDA after 6 months in TCZ group. CONCLUSIONS: Obesity influences the extent of LDA/remission in patients treated with TNFi, but not in patients treated with TCZ, probably because of underlying pathophysiological mechanisms intrinsic to the production of proinflammatory adi-pokines. Therefore, therapeutic strategies with a mechanism of action other than TNF inhibition would be more suitable for obese patients.

Prevalence and significance of ischemic cerebrovascular events in giant cell arteritis

Objectives: To determine the prevalence of cerebrovascular events (CVE) in giant cell arteritis (GCA) and to alert clinicians to the importance of early detection of CVE in this disease.MethodsRetrospective observational study involving a cohort of GCA patients. Demographic, clinical and laboratory data were collected. All patients fulfilled the American College of Rheumatology (ACR) 1990 GCA classification criteria and had a positive ultrasound test for GCA in agreement with the EULAR recommendations. Demographic and clinical parameters were recorded with special attention paid to ischemic cranial events.ResultsWe studied 123 consecutive GCA patients, 74 (60.2%) women with a mean age of 79 years. Twelve patients (9.75%) suffered from neurologic symptoms other than AION, of whom 9 (7.3%) experienced ischemic events related to GCA and 3 (2.44%) likely experienced CVE due to other common causes. Of the 9 patients with CVE caused by GCA, 5 were diagnosed with transient ischemic attacks (TIAs), 2 with ischemic stroke, and 2 were cases involving cranial nerve palsies. High rates of mortality were found in patients with a TIA or stroke, while polymyalgia rheumatica (PMR) appeared to confer some protection against ischemic pathologies in GCA patients.ConclusionsStroke and TIA are common presentation patterns associated with GCA and should be suspected in all CVE-related cases with high acute-phase reactants commonly present in the elderly. This ischemic subgroup exhibited a higher mortality rate. (AU)

Objetivos: Determinar la prevalencia de los accidentes cerebrovasculares (ACV) en la arteritis de células gigantes (ACG) y alertar a los facultativos sobre la importancia de la detección temprana de los ACV en esta enfermedad.MétodosEstudio observacional retrospectivo que incluyó una cohorte de pacientes de ACV. Se recabaron los datos demográficos, clínicos y de laboratorio. Todos los pacientes cumplieron los criterios de clasificación de ACV del American College of Rheumatology de 1990, y su ecografía fue positiva para ACG con arreglo a las recomendaciones EULAR. Se registraron los parámetros demográficos y clínicos, prestándose especial atención a los episodios cerebrales de isquemia.ResultadosEstudiamos 123 pacientes consecutivos de ACG, de los que 74 (60,2%) eran mujeres, con una edad media de 79 años. Doce pacientes (9,75%) tenían síntomas neurológicos distintos a AION, de los cuales 9 (7,3%) evidenciaron episodios isquémicos relacionados con ACG y 3 (2,44%) experimentaron previsiblemente ACV debido a causas comunes. De los 9 pacientes con ACV causado por ACG, 5 fueron diagnosticados de accidente isquémico transitorio (AIT), 2 de accidente isquémico y otros 2 de parálisis del nervio craneal. Se encontraron altas tasas de mortalidad en los pacientes con AIT o ictus, mientras que la polimialgia reumática pareció conferir cierta protección frente a afecciones isquémicas en los pacientes de ACG.ConclusionesLos ictus y los AIT son patrones de presentación comunes asociados a ACG y deberían sospecharse en todos los casos relacionados con ACV con altos reactantes de fase aguda que se presentan comúnmente en los ancianos. Este subgrupo isquémico reflejó una alta tasa de mortalidad. (AU)

Prevalence and significance of ischemic cerebrovascular events in giant cell arteritis.

OBJECTIVES: To determine the prevalence of cerebrovascular events (CVE) in giant cell arteritis (GCA) and to alert clinicians to the importance of early detection of CVE in this disease. METHODS: Retrospective observational study involving a cohort of GCA patients. Demographic, clinical and laboratory data were collected. All patients fulfilled the American College of Rheumatology (ACR) 1990 GCA classification criteria and had a positive ultrasound test for GCA in agreement with the EULAR recommendations. Demographic and clinical parameters were recorded with special attention paid to ischemic cranial events. RESULTS: We studied 123 consecutive GCA patients, 74 (60.2%) women with a mean age of 79 years. Twelve patients (9.75%) suffered from neurologic symptoms other than AION, of whom 9 (7.3%) experienced ischemic events related to GCA and 3 (2.44%) likely experienced CVE due to other common causes. Of the 9 patients with CVE caused by GCA, 5 were diagnosed with transient ischemic attacks (TIAs), 2 with ischemic stroke, and 2 were cases involving cranial nerve palsies. High rates of mortality were found in patients with a TIA or stroke, while polymyalgia rheumatica (PMR) appeared to confer some protection against ischemic pathologies in GCA patients. CONCLUSIONS: Stroke and TIA are common presentation patterns associated with GCA and should be suspected in all CVE-related cases with high acute-phase reactants commonly present in the elderly. This ischemic subgroup exhibited a higher mortality rate.

Respuesta a: Estudio comparativo de la ecografía Doppler frente a la biopsia de arteria temporal en el diagnóstico de la arteritis de células gigantes / Response to: A comparative study of doppler ultrasound against temporal artery biopsy in the diagnosis of giant cell arteritis

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Circulating CD19+CD24hiCD38hi regulatory B cells as biomarkers of response to methotrexate in early rheumatoid arthritis.

OBJECTIVE: The protagonism of regulatory B cells seems to vary along the course of the disease in murine models of inflammatory conditions. Decreased numbers of circulating regulatory CD19+CD24hiCD38hi transitional (cTr) B cells have been described in patients with long-standing RA, thus our objective was to examine the frequency and evolution of cTr B cells in the peripheral blood of early RA (ERA) patients. METHODS: Freshly isolated peripheral blood mononuclear cells from 48 steroid- and DMARD-naïve ERA patients with a disease duration of <24 weeks and 48 healthy controls (HCs) were examined by flow cytometry. Co-cultures of isolated memory B cells were established with autologous T cells in the absence or presence of Tr B cells. RESULTS: As compared with HCs, ERA patients demonstrated an increased frequency of cTr B cells. cTr B cells of ERA patients and HCs displayed an anti-inflammatory cytokine profile and were able to downregulate T cell IFN-γ and IL-21 production, together with ACPA secretion in autologous B/T cell co-cultures. Basal frequencies of cTr B cells above the median value observed in HCs were associated with a good EULAR response to MTX at 12 months [relative risk 2.91 (95% CI 1.37, 6.47)]. A significant reduction of cTr B cells was observed 12 months after initiating MTX, when the cTr B cell frequency was no longer elevated but decreased, and this was independent of the degree of clinical response or the intake of prednisone. CONCLUSION: An increased frequency of regulatory cTr B cells is apparent in untreated ERA and the baseline cTr B cell frequency is associated with the clinical response to MTX at 12 months.

Two populations of circulating PD-1hiCD4 T cells with distinct B cell helping capacity are elevated in early rheumatoid arthritis.

OBJECTIVE: A novel population of B helper cells, phenotypically CD4+CXCR5-PD-1hi, has been described in the synovial tissues and peripheral blood of seropositive RA patients, and termed 'peripheral helper T' (Tph) cells. Contrary to CD4+CXCR5+PD-1hi follicular helper T (Tfh), Tph cells are not located in lymphoid organs but accumulate in inflamed tissues. Our objective was to study the frequency of circulating Tph (cTph) and circulating Tfh cell counterparts (cTfh) in patients with early RA (eRA). METHODS: Freshly isolated peripheral blood mononuclear cells from 56 DMARD-naïve eRA patients and 56 healthy controls were examined by flow cytometry. Autologous cocultures of naïve or memory B cells were established with isolated peripheral blood Tph or Tfh cells. RESULTS: Seropositive (RF+ and/or ACPA+, n = 38) but not seronegative eRA patients (n = 18) demonstrated increased frequencies and absolute numbers of cTph and cTfh cells. cTph but not cTfh cells expressed CCR2. Those eRA patients who experienced a significant clinical improvement at 12 months demonstrated a marked decrease of their cTph cell numbers whereas their cTfh cell numbers remained unchanged. Both isolated Tph and isolated Tfh cells were able to induce maturation of memory B cells, whereas only Tfh cells could differentiate naïve B cells. CONCLUSION: Two populations of PD-1hiCD4 T cells with distinct phenotype and B cell helping capacity are increased in the peripheral blood of seropositive eRA patients. Whereas cTph cells are present only in patients with an active disease, cTfh cells seem to be constitutively elevated.

The effect of methotrexate versus other disease-modifying anti-rheumatic drugs on serum drug levels and clinical response in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors.

To investigate the effect of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with adalimumab or infliximab on maintaining serum drug and clinical outcomes after the first year of treatment in patients with rheumatoid arthritis (RA). Second, to assess the influence of methotrexate (MTX) dose on these outcomes. Ninety-two patients with RA starting infliximab (n = 67) or adalimumab (n = 25) tumor necrosis factor inhibitor (TNFi) with available drug levels and clinical improvement assessment (European League Against Rheumatism [EULAR] response) after 12 months were included. Patients were grouped according to concomitant csDMARD use: (i) TNFi monotherapy; (ii) TNFi+MTX; (iii) TNFi with csDMARDs other than MTX (TNFi+OD). Patients receiving MTX were also classified by dose as < 15 mg/week (TNFi+MTX<15) and ≥ 15 mg/week (TNFi+MTX≥15). Logistic regression analyses were employed. More TNFi+MTX patients had circulating serum TNFi at 12 months (71% TNFi+MTX vs. 20% TNFi+OD vs. 9% TNFi monotherapy). Of these, the probability of maintaining serum TNFi levels was twice (OR 2.3; p = 0.06) than that of patients without MTX. However, statistically significant results were observed only for the highest MTX dose (OR 4.9; p = 0.02). Most patients achieving good EULAR response were treated with TNFi+MTX (81%). The probability of achieving this response was three times higher in patients within the TNFi+MTX group (OR 3.4; p = 0.03); however, no differences were found with regard to MTX dose. The persistence of serum TNFi and the probability of achieving clinical response are influenced by MTX but not by OD in patients with RA treated with infliximab or adalimumab.