Toward Telemonitoring in Immune-Mediated Inflammatory Diseases: Protocol for a Mixed Attention Model Study.

BACKGROUND: Rheumatic and musculoskeletal diseases (RMDs) are chronic diseases that may alternate between asymptomatic periods and flares. These conditions require complex treatments and close monitoring by rheumatologists to mitigate their effects and improve the patient's quality of life. Often, delays in outpatient consultations or the patient's difficulties in keeping appointments make such close follow-up challenging. For this reason, it is very important to have open communication between patients and health professionals. In this context, implementing telemonitoring in the field of rheumatology has great potential, as it can facilitate the close monitoring of patients with RMDs. The use of these tools helps patients self-manage certain aspects of their disease. This could result in fewer visits to emergency departments and consultations, as well as enable better therapeutic compliance and identification of issues that would otherwise go unnoticed. OBJECTIVE: The main objective of this study is to evaluate the implementation of a hybrid care model called the mixed attention model (MAM) in clinical practice and determine whether its implementation improves clinical outcomes compared to conventional follow-up. METHODS: This is a multicenter prospective observational study involving 360 patients with rheumatoid arthritis (RA) and spondylarthritis (SpA) from 5 Spanish hospitals. The patients will be followed up by the MAM protocol, which is a care model that incorporates a digital tool consisting of a mobile app that patients can use at home and professionals can review asynchronously to detect incidents and follow patients' clinical evolution between face-to-face visits. Another group of patients, whose follow-up will be conducted in accordance with a traditional face-to-face care model, will be assessed as the control group. Sociodemographic characteristics, treatments, laboratory parameters, assessment of tender and swollen joints, visual analog scale for pain, and electronic patient-reported outcome (ePRO) reports will be collected for all participants. In the MAM group, these items will be self-assessed via both the mobile app and during face-to-face visits with the rheumatologist, who will do the same for patients included in the traditional care model. The patients will be able to report any incidence related to their disease or treatment through the mobile app. RESULTS: Participant recruitment began in March 2024 and will continue until December 2024. The follow-up period will be extended by 12 months for all patients. Data collection and analysis are scheduled for completion in December 2025. CONCLUSIONS: This paper aims to provide a detailed description of the development and implementation of a digital solution, specifically an MAM. The goal is to achieve significant economic and psychosocial impact within our health care system by enhancing control over RMDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT06273306; https://clinicaltrials.gov/ct2/show/NCT06273306. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55829.

Exploring the influence of baseline rheumatoid factor levels on TNF inhibitor retention rate in patients with rheumatoid arthritis: a multicentre and retrospective study.

OBJECTIVE: To assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels. METHODS: Longitudinal, retrospective and multicentre study including patients with RA who were treated with any TNFi (monoclonal antibodies (mAB), etanercept (ETA) or CZP). Log-rank test and Cox regressions were conducted to evaluate the retention rate in the three groups according to the level of RF, with the third quartile of the baseline levels used as cut-off: <200 (

Circulating Tfh cells are differentially modified by abatacept or TNF blockers, and predict treatment response in Rheumatoid Arthritis.

OBJECTIVE: CD4+CXCR5+PD-1hi follicular helper T (Tfh) cells dwell in the germinal centers (GCs) of lymphoid organs and participate in Rheumatoid Arthritis (RA) pathogenesis; the frequency of their circulating counterparts (cTfh-frequency) is expanded in RA and correlates with the pool of GC Tfh cells. Our objective was to study the effect of abatacept (ABT) or TNF blockers (TNFb) on the cTfh-frequency in RA. METHODS: Peripheral blood was drawn from seropositive-longstanding RA patients chronically receiving csDMARDS (n = 45), TNFb (n = 59), or ABT (n = 34), and healthy controls (HC) (n = 137). Also, patients with an incomplete response to csDMARDS (n = 41) who initiated TNFb (n = 19) or ABT (n = 22), were studied at 0 and 12 months. The cTfh-frequency was examined by cytometry. RESULTS: As compared with HC, an increased cTfh-frequency was seen in seropositive-longstanding RA chronically receiving csDMARDs or TNFb but not ABT. After escalating from csDMARDs, the cTfh-frequency did not vary in patients who were given TNFb but decreased to HC levels in those given ABT. In the ABT group, the baseline cTfh-frequency was higher for patients who attained 12M remission (12Mr), vs those who remained active (12Ma): 0m cutoff for remission >0.38% (Sens. 92%, Sp. 90%), OR 25.3. Conversely, in the TNFb group, the baseline cTfh-frequency was lower for 12Mr vs 12Ma: 0m cutoff for non-remission >0.44% (Sens. 67%, Sp. 90%), OR 8.5. CONCLUSION: ABT but not TNFb, is able to curtail the cTfh-frequency in RA. A higher baseline cTfh-frequency predicts a good response to ABT but a poor response to TNFb.

Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling.

Introduction: RA patients are at higher risk of cardiovascular disease, influenced by therapies. Studying their cardiovascular and cardiometabolic proteome can unveil biomarkers and insights into related biological pathways. Methods: This study included two cohorts of RA patients: newly diagnosed individuals (n=25) and those with established RA (disease duration >25 years, n=25). Both cohorts were age and sex-matched with a control group (n=25). Additionally, a longitudinal investigation was conducted on a cohort of 25 RA patients treated with methotrexate and another cohort of 25 RA patients treated with tofacitinib for 6 months. Clinical and analytical variables were recorded, and serum profiling of 184 proteins was performed using the Olink technology platform. Results: RA patients exhibited elevated levels of 75 proteins that might be associated with cardiovascular disease. In addition, 24 proteins were increased in RA patients with established disease. Twenty proteins were commonly altered in both cohorts of RA patients. Among these, elevated levels of CTSL1, SORT1, SAA4, TNFRSF10A, ST6GAL1 and CCL18 discriminated RA patients and HDs with high specificity and sensitivity. Methotrexate treatment significantly reduced the levels of 13 proteins, while tofacitinib therapy modulated the expression of 10 proteins. These reductions were associated with a decrease in DAS28. Baseline levels of SAA4 and high levels of BNP were associated to the non-response to methotrexate. Changes in IL6 levels were specifically linked to the response to methotrexate. Regarding tofacitinib, differences in baseline levels of LOX1 and CNDP1 were noted between non-responder and responder RA patients. In addition, response to tofacitinib correlated with changes in SAA4 and TIMD4 levels. Conclusion: In summary, this study pinpoints molecular changes linked to cardiovascular disease in RA and proposes candidate protein biomarkers for distinguishing RA patients from healthy individuals. It also highlights how methotrexate and tofacitinib impact these proteins, with distinct alterations corresponding to each drug's response, identifying potential candidates, as SAA4, for the response to these therapies.

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.

Influence of rheumatoid factor on serum drug levels of tumour necrosis factor inhibitors with different structures in rheumatoid arthritis.

OBJECTIVES: Certolizumab pegol (CZP), an Fc-free antibody fragment, has shown stable serum levels and steady efficacy in the treatment of RA patients, irrespective of RF levels at baseline. Here, we examine, in clinical practice, the effect of baseline RF and ACPA levels on serum drug levels of IFX, ADL and CZP an Fc-free antibody fragment. METHODS: This is a retrospective study performed in real-world patients. We assessed 170 patients with RA: 90 (53%) received IFX, 48 (28%) ADL and 32 (19%) CZP. Demographic and clinical variables, RF and ACPA levels were obtained at the baseline visit (T0), and patients were stratified based on negative, low, medium, or high levels. After 6 months (T6) serum drug levels and anti-drug antibodies (ADAb), were computed. RESULTS: While CZP serum levels did not differ across RF groups at T6, high baseline RF was linked to lower serum drug levels compared to RF negative status in treatment with complete monoclonal antibodies IFX and ADL. No differences in disease activity measured by DAS28 at baseline were observed across RF quartiles in patients treated with IFX or ADL. ADAb was observed in 26 patients with IFX, 3 with ADL and 1 with CZP, following 6 months of treatment. Patients with high baseline RF levels dropped out more frequently by secondary non-response in IFX or ADL than CZP (80% vs. 75% vs. 33%, p=0.002). CONCLUSIONS: In this real word data evaluation, CZP serum levels were independent of RF levels in patients however patients with high baseline RF levels who obtained IFX or ADL had lower serum drug levels at 6 months than baseline RF-negative patients. In addition, secondary non-response was more frequent in patients with high RF levels treated with IFX and ADL.

Recomendaciones SER sobre la gestión de riesgo del tratamiento con FAME biológicos o sintéticos dirigidos en pacientes con artritis reumatoide / Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis

Objetivo: Elaborar recomendaciones basadas en la evidencia disponible y el consenso de expertos, para la gestión del riesgo del tratamiento biológico y los inhibidores de las JAK en pacientes con artritis reumatoide. Métodos: Se identificaron preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO (paciente, intervención, comparación, outcome o desenlace) por un panel de expertos, seleccionados en base a su experiencia en el área. Se realizó una revisión sistemática de la evidencia, graduándose de acuerdo a los criterios GRADE (Grading of Recommendations Assessment, Development, and Evaluation). A continuación, se formularon las recomendaciones específicas. Resultados: Se propusieron por el panel de expertos 6preguntas PICO en base a su relevancia clínica y a la existencia de información reciente referentes al riesgo de aparición de infecciones graves, el riesgo de reactivación del virus de la hepatitisB, el riesgo de reactivación del virus varicela-zoster, el riesgo de aparición de cáncer de piel (melanoma y no melanoma) o hematológico, el riesgo de aparición de enfermedad tromboembólica y el riesgo de progresión del virus del papiloma humano. Se formularon un total de 29 recomendaciones, estructuradas por pregunta, basadas en la evidencia encontrada y el consenso de los expertos. Conclusiones: Se presentan las recomendaciones SER sobre la gestión del riesgo del tratamiento con terapias biológicas e inhibidores de las JAK en la artritis reumatoide.(AU)

Objective: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. Methods: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. Results: Six PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitisB virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or hematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 29 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. Conclusions: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.(AU)

Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis.

OBJECTIVE: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. METHODS: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome or outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. RESULTS: 6 PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitis B virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or haematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 28 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. CONCLUSIONS: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.

Teleconsultation in rheumatology: A literature review and opinion paper.

In this article, we review published literature on "telerheumatology", a term describing the use of telemedicine in rheumatology. This field has received considerable recent attention through the development of efficient digital technologies, resulting in a good level of satisfaction among patients and health care professionals. In 2020, the social distancing constraints during the COVID-19 pandemic accelerated more widespread adoption worldwide. Telerheumatology is particularly suited for patients with rheumatoid arthritis who have achieved a sustained therapeutic target of remission or low disease activity. To facilitate remote consultations and meet expectations of rheumatologists and patients, international and national guidelines have recently been proposed and existing tools, such as Patient-Reported Outcomes questionnaires, have had to be digitally adapted. In addition, telerheumatology toolkits are proposed by the Arab League of Associations for Rheumatology (ArLAR), the Association of American Medical College (AAMC), and the American College of Rheumatology (ACR) for all learners, from medical students to practicing clinicians, encouraging the acquisition of telehealth skills and facilitating their integration into their routine clinical practice. The main benefits reported for this mode of health care are greater access to specialty care, flexibility, reduced rates of missed appointments, as well as improved patient engagement and autonomy. Limitations include the absence of physical examination. However, to implement telerheumatology effectively and widely in daily clinical practice, some barriers still need to be addressed. These include training of health care professionals, technological restrictions and reimbursement mechanisms. Despite the advantages of telerheumatology, it is not intended to replace face-to-face visits, but rather as a way to enhance access to care, service delivery and health care support for patients.

Translation and cross-cultural adaptation of the mSQUASH into Spanish.

BACKGROUND: There is a lack of outcome measures for the assessment of physical activity in patients with axial spondyloarthritis (axSpA). For this matter, the modified Short QUestionnaire to Assess Health (mSQUASH) was developed and validated, originally in Dutch. OBJECTIVE: To translate and cross-culturally adapt the mSQUASH into Spanish and to evaluate the equivalence of the translated version in patients with axSpA. METHODS: The mSQUASH was translated following forward-backward procedure according to the protocol of Beaton. Two bi-lingual translators produced independent forward translations of the mSQUASH into Spanish, and the versions were harmonized in a consensual version. Another translator back translated the synthesized version into Dutch. A scientific committee reached consensus on discrepancies and developed a pre-final version of the questionnaire. The field test with cognitive debriefing involved 10 patients with axSpA with different gender, age, disease duration, educational level and working status. RESULTS: The translation process of the mSQUASH was completed without major issues. The first translation needed several iterations due to small discrepancies in the wording. Back-translation was performed without difficulties, and the scientific committee agreed upon a final version of the questionnaire. Cognitive debriefing showed the Spanish questionnaire to be clear, relevant, understandable and comprehensive. The preliminary version was accepted with minor modifications. CONCLUSIONS: The resulting Spanish version of the mSQUASH showed good linguistic and face validity according to the field test, revealing potential for use in clinical practice and research. In order to conclude the cross-cultural adaptation of the mSQUASH into Spanish, the next step is the assessment of psychometric properties of the Spanish version.

Translation and cross-cultural adaptation of the mSQUASH into Spanish / Traducción y adaptación transcultural del mSQUASH al español

Background: There is a lack of outcome measures for the assessment of physical activity in patients with axial spondyloarthritis (axSpA). For this matter, the modified Short QUestionnaire to Assess Health (mSQUASH) was developed and validated, originally in Dutch. Objective: To translate and cross-culturally adapt the mSQUASH into Spanish and to evaluate the equivalence of the translated version in patients with axSpA. Methods: The mSQUASH was translated following forward-backward procedure according to the protocol of Beaton. Two bi-lingual translators produced independent forward translations of the mSQUASH into Spanish, and the versions were harmonized in a consensual version. Another translator back translated the synthesized version into Dutch. A scientific committee reached consensus on discrepancies and developed a pre-final version of the questionnaire. The field test with cognitive debriefing involved 10 patients with axSpA with different gender, age, disease duration, educational level and working status. Results: The translation process of the mSQUASH was completed without major issues. The first translation needed several iterations due to small discrepancies in the wording. Back-translation was performed without difficulties, and the scientific committee agreed upon a final version of the questionnaire. Cognitive debriefing showed the Spanish questionnaire to be clear, relevant, understandable and comprehensive. The preliminary version was accepted with minor modifications. Conclusions: The resulting Spanish version of the mSQUASH showed good linguistic and face validity according to the field test, revealing potential for use in clinical practice and research. In order to conclude the cross-cultural adaptation of the mSQUASH into Spanish, the next step is the assessment of psychometric properties of the Spanish version. (AU)

Antecedentes: Las medidas de resultado para la evaluación de la actividad física en pacientes con espondiloartritis axial (EspAax) son escasas. Por ello, se desarrolló y validó el modified Short QUestionnaire to Assess Health (mSQUASH), originalmente en holandés. Objetivo: Desarrollar el proceso de traducción y adaptación transcultural del mSQUASH al español, y evaluar la equivalencia de la versión traducida en pacientes con EspAax. Métodos: El mSQUASH se tradujo siguiendo el procedimiento adelante-atrás según el protocolo de Beaton. Dos traductores bilingües realizaron traducciones directas independientes del mSQUASH al español, y las versiones se armonizaron en una versión consensuada. Otro traductor volvió a traducir la versión sintetizada al holandés. Un comité científico llegó a un consenso sobre las discrepancias y elaboró una versión pre-final del cuestionario. En las entrevistas cognitivas participaron 10 pacientes con EspAax de diferente sexo, edad, duración de la enfermedad, nivel educativo y situación laboral. Resultados: El proceso de traducción del mSQUASH se completó sin problemas mayores. La primera traducción necesitó varias iteraciones debido a pequeñas discrepancias en la redacción. La traducción inversa se realizó sin dificultades y el comité científico acordó la versión final del cuestionario. La evaluación cognitiva demostró que el cuestionario en español era claro, pertinente, comprensible y completo. La versión preliminar fue aceptada con pequeñas modificaciones. Conclusiones: La versión española resultante del mSQUASH mostró una buena validez lingüística y aparente, revelando potencial para su uso en práctica clínica e investigación. Para concluir la adaptación transcultural del mSQUASH al español, el siguiente paso es la evaluación de las propiedades psicométricas de la versión española. (AU)

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.

Effect of Filgotinib on Body Mass Index (BMI) and Effect of Baseline BMI on the Efficacy and Safety of Filgotinib in Rheumatoid Arthritis.

INTRODUCTION: This post hoc analysis of the phase 3 rheumatoid arthritis (RA) filgotinib clinical trial program assessed the effect of filgotinib on body mass index (BMI) in patients with RA and the impact of BMI on the efficacy and safety of filgotinib. METHODS: FINCH 1-3 were randomized, double-blind, active- or placebo-controlled phase 3 trials of filgotinib 100 and 200 mg in patients with RA (N = 3452). BMI assessments included the mean change from baseline in BMI and the proportion of patients whose BMI increased by incremental thresholds. Efficacy measures included American College of Rheumatology (ACR) 20/50/70 response and low disease activity/remission according to Disease Activity Score 28 using C-reactive protein. The exposure-adjusted incident rate (EAIR) of adverse events (AEs) was assessed by baseline BMI, using integrated data from the FINCH 1-4 and the phase 2 DARWIN 1-3 studies (total filgotinib exposure = 8085 patient-years). RESULTS: Mean change from baseline in BMI over time was similar across treatment arms. In most patients, BMI increased by ≤ 1 or 2 kg/m2 at both weeks 12 and 24, regardless of treatment group or baseline BMI; few patients had increases of ≥ 4 kg/m2. For most efficacy measures, filgotinib 200 mg was more efficacious than filgotinib 100 mg or active comparators or placebo across BMI subgroups. For the higher filgotinib dose, the EAIR of serious treatment-emergent AEs, venous thrombotic and embolic events, and major adverse cardiovascular events increased with increasing BMI. CONCLUSIONS: Filgotinib did not lead to substantial changes in BMI, and BMI did not appear to affect the efficacy of filgotinib. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02889796, NCT02873936, NCT02886728, NCT03025308, NCT01888874, NCT01894516, NCT02065700.

Some rheumatoid arthritis treatments cause patients to gain weight or are less effective in patients with obesity than in patients without obesity. Also, obesity can make rheumatoid arthritis worse. Filgotinib is a rheumatoid arthritis treatment that was evaluated in seven randomized clinical studies (FINCH 1­4 and DARWIN 1­3). We investigated whether filgotinib causes changes in weight and whether body mass index (BMI) affects the efficacy or safety of filgotinib. We analyzed how the BMI of patients who participated in FINCH 1, 2, or 3 changed over time. Most patients had a small increase in BMI (around 1­2 kg/m²) after 24 weeks of filgotinib treatment. This change in BMI was not affected by patients' BMI at baseline. Baseline BMI did not impact the efficacy of filgotinib, which was assessed using standard measures of disease activity. Filgotinib was more effective than other rheumatoid arthritis treatments and placebo in all patients, regardless of BMI subgroup. Using safety data from all seven clinical studies (FINCH 1­4 and DARWIN 1­3), we found that some adverse events occurred more often in patients with obesity (a BMI of ≥ 30 kg/m²) than in those without obesity. The increased adverse events included venous thrombotic and embolic events and major adverse cardiovascular events, for which obesity is a known risk factor. These results show that filgotinib did not substantially change BMI (which increased by around 1­2 kg/m² in most patients), and that baseline BMI did not affect the efficacy of filgotinib.

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.

Coping with rheumatic stressors (CORS) questionnaire: Spanish translation and cross-cultural adaptation.

BACKGROUND: Rheumatic and Musculoskeletal Diseases (RMDs) substantially impact the lives of patients, with complex associations between disease severity and self-perceived health status. In this regard, the Coping with Rheumatic Stressors (CORS) questionnaire was developed to measure how patients with RMDs cope with stressors such as pain, limitations or dependency. The CORS is not currently available in Spanish, and therefore the adaptation of this instrument is needed. OBJECTIVE: First, to cross-culturally adapt the CORS into Spanish for Spain. Secondly, to test the conceptual equivalence of the translated version in patients with axial spondyloarthritis (axSpA). METHODS: A translation of the CORS into Spanish was performed adhering to the forward-backward procedure described by Beaton. Two translators produced independent forward translations of the item content, response options, and instructions of the CORS into Spanish. Both versions were harmonized in a consensual version. Another translator back-translated the synthesized version into Dutch. A scientific committee including all the translators, one methodologist and a rheumatologist, held a meeting and reached consensus on discrepancies to develop a final draft version of the Spanish CORS. Then, a field test with cognitive debriefing was conducted, involving a sample of 10 patients with axSpA. RESULTS: The translation process of the CORS was completed after the discussion of some discrepancies throughout the process. The first translation was done without major complications. Back-translation presented some discrepancies. These led to minor modifications in the wording in one response option and 15 questionnaire items. The scientific committee agreed upon a final version of the questionnaire. Cognitive debriefing, led to minor modifications; for example, three respondents indicated that one of the statements in the instructions was syntactically complex ("indique cuán a menudo usted ha llevado a cabo dicho comportamiento") which led to its adjustment. The process indicated that the final CORS Spanish questionnaire was clear and understandable to all patients. CONCLUSIONS: The Spanish version of the CORS showed good cross-cultural validity and good face validity according to the field test. Before the Spanish CORS is implemented, further validation is in progress to test the psychometric properties of the instrument in patients with axSpA.

EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVE: To develop EULAR points-to-consider for therapeutic drug monitoring (TDM) of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases (RMDs). METHODS: The points-to-consider were developed in accordance with EULAR standardised operation procedures by a multidisciplinary task force from eight European countries, based on a systematic literature review and expert consensus. Level of evidence and strength of the points-to-consider were determined, and mean levels of agreement among the task force were calculated using a 10-point rating scale. RESULTS: Six overarching principles and 13 points-to-consider were formulated. The level of agreement among the task force for the overarching principles and points-to-consider ranged from 8.4 to 9.9.The overarching principles define TDM and its subtypes, and reinforce the underlying pharmacokinetic/pharmacodynamic principles, which are relevant to all biopharmaceutical classes. The points-to-consider highlight the clinical utility of the measurement and interpretation of biopharmaceutical blood concentrations and antidrug antibodies in specific clinical scenarios, including factors that influence these parameters. In general, proactive use of TDM is not recommended but reactive TDM could be considered in certain clinical situations. An important factor limiting wider adoption of TDM is the lack of both high quality trials addressing effectiveness and safety of TDM and robust economic evaluation in patients with RMDs. Future research should focus on providing this evidence, as well as on further understanding of pharmacokinetic and pharmacodynamic characteristics of biopharmaceuticals. CONCLUSION: These points-to-consider are evidence-based and consensus-based statements for the use of TDM of biopharmaceuticals in inflammatory RMDs, addressing the clinical utility of TDM.

Serum leptin concentration is associated with the attainment of clinical outcomes in patients with axial spondyloarthritis treated with TNF inhibitors.

OBJECTIVES: To analyse the influence of adipokines on attaining the clinical outcomes in patients with axial spondyloarthritis (axSpA) treated with TNF inhibitors (TNFi), and then, to investigate the association of patients' characteristics and adipokine concentrations. METHODS: This was a longitudinal study including 110 patients with axSpA who were initiated at TNFi and were followed-up for 6 months (m). Disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline and at 6 m of treatment. Clinical outcomes at 6 m of treatment were defined as remission (ASDAS <1.3) and the attainment of low disease activity (LDA; ASDAS<2.1). Leptin and adiponectin concentrations were measured in serum samples collected at baseline and after 6 m. RESULTS: Both leptin and adiponectin were constitutively elevated in female axSpA patients. At time of TNFi initiation, leptin concentrations were higher in patients with high body mass index (overweight or obese). On the contrary, adiponectin was higher in normalweight patients. After 6 m of TNFi treatment, 24% of patients attained remission. They had significant lower leptin concentration at baseline compared with patients who did not attain remission. Furthermore, this difference remained significant after 6 m of treatment meaning that TNFi did not modify adipokine concentration. Similar results were found considering LDA as the clinical outcome, obtained in 48% of the patients. CONCLUSIONS: The present study showed that low leptin concentrations were associated with attaining clinical outcomes in axSpA patients treated with TNFi. In addition, since leptin secretion by white adipocytes is enhanced during obesity and considering that TNFi do not seem to modulate its expression, obese patients should be encouraged to decrease BMI to attain a successful therapy.

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.