Pan American League of Associations for Rheumatology Recommendations for the Treatment of Psoriatic Arthritis.

OBJECTIVE: Psoriatic arthritis (PsA) is chronic disease that compromises multiple domains and might be associated with progressive joint damage, increased mortality, functional limitation, and considerably impaired quality of life. Our objective was to generate evidence-based recommendations on the management of PsA in Pan American League of Associations for Rheumatology (PANLAR) countries. METHODS: We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to adapt the 2019 recommendations of the European Alliance of Associations for Rheumatology. A working group consisting of rheumatologists from various countries in Latin America identified relevant topics for the treatment of PsA in the region. The methodology team updated the evidence and synthesized the information used to generate the final recommendations. These were then discussed and defined by a panel of 31 rheumatologists from 15 countries. RESULTS: Theses guidelines report 15 recommendations addressing therapeutic targets, use of antiinflammatory agents and corticosteroids, treatment with disease-modifying antirheumatic drugs (conventional synthetic, biologic, and targeted synthetic), therapeutic failure, optimization of biologic therapy, nonpharmacological interventions, assessment tools, and follow-up of patients with PsA. CONCLUSION: Here we present a set of recommendations to guide decision making in the treatment of PsA in Latin America, based on the best evidence available, considering resources, medical expertise, and the patient's values and preferences. The successful implementation of these recommendations should be based on clinical practice conditions, healthcare settings in each country, and a tailored evaluation of patients.

Tasas de promoción, repitencia y abandono en la Carrera de Especialistas en Reumatología en la Ciudad de Buenos Aires / Specialty training in rheumatology: Promotion, repetition and dropout rates in the city of Buenos Aires

Objetivos: Evaluar la trayectoria de los alumnos de la Carrera de Especialistas en Reumatología y determinar factores asociados al resultado en el posgrado. Métodos: Análisis retrospectivo (2009-2016). Se determinaron las tasas de promoción, la repitencia y el abandono. Se realizaron análisis multivariados para determinar variables asociadas al éxito académico. Resultados: Sobre 119 alumnos, la promoción efectiva fue del 66,4%, la repitencia sin retraso fue del 14,3%, la repitencia con retraso fue del 11,8% y el abandono fue del 7,6%. La promoción efectiva de la residencia fue del 82,5% vs el 48,2% en el resto (p<0,001), la repitencia con retraso fue del 3,2% vs el 21,4% en el resto (p=0,005) y el abandono fue del 3,2% vs el 12,5% en el resto (p=0,06). El éxito en el posgrado fue mayor a mejor promedio en la carrera de Medicina (OR: 3,41; IC95%: 2,0-6,4; p<0,001). Conclusiones: La residencia se asoció a mayor éxito académico en el posgrado. El puntaje promedio en la cursada de Medicina puede ayudar a identificar a los alumnos en riesgo de fallar.(AU)

Objectives: To evaluate the trajectory of students enrolled in the specialty training in rheumatology. Methods: Retrospective analysis (2009-2016). Promotion, repetition, and dropout rates were determined. Analysis was performed to define variables associated with academic success. Results: Out of 119 students, the actual promotion rate was 66.4%, 11.8% failed an exam (at least) and completed the course after the stipulated time, and the dropout rate was 7.6%. Among residents, the promotion rate was 82.5% vs. 48.2% among the rest (P<.001), the lagging students’ repetition rate was 3.2% vs. 21.4% among the rest (P=.005), and the dropout rate was 3.2% vs. 12.5% among the rest (P=.06). A higher average score in medical school increased the chances of success in the postgraduate programme (OR: 3.41; 95%CI: 2.0-6.4; P<.001). Conclusions: The residency was associated with higher rates of academic success in postgraduate studies. The average score in medical school can help identify students at risk of failure.(AU)

Speciality training in rheumatology: Promotion, repetition and dropout rates in the city of Buenos Aires.

OBJECTIVES: To evaluate the trajectory of students enrolled in the specialty training in rheumatology. METHODS: Retrospective analysis (2009-2016). Promotion, repetition, and dropout rates were determined. Analysis was performed to define variables associated with academic success. RESULTS: Out of 119 students, the actual promotion rate was 66.4%, 11.8% failed an exam (at least) and completed the course after the stipulated time, and the dropout rate was 7.6%. Among residents, the promotion rate was 82.5% vs. 48.2% among the rest (p < 0.001), the lagging students' repetition rate was 3.2% vs. 21.4% among the rest (p 0.005), and the dropout rate was 3.2% vs. 12.5% among the rest (p = 0.06). A higher average score in medical school increased the chances of success in the postgraduate programme (OR 3.41 CI 95% 2.0-6.4; p < 0.001). CONCLUSIONS: The residency was associated with higher rates of academic success in postgraduate studies. The average score in medical school can help identify students at risk of failure.

Tofacitinib Efficacy in Patients with Rheumatoid Arthritis and Probable Depression/Anxiety: Post Hoc Analysis of Phase 3 and 3b/4 Randomized Controlled Trials.

INTRODUCTION: The aim of our work is to assess the prevalence of probable major depressive disorder and/or probable generalized anxiety disorder (pMDD/pGAD) in patients with moderate to severe rheumatoid arthritis (RA), and to evaluate the efficacy of tofacitinib on RA symptoms stratified by baseline pMDD/pGAD status. METHODS: Data were pooled from five phase 3 randomized controlled trials (RCTs) and one phase 3b/4 RCT, assessing tofacitinib 5 or 10 mg twice daily (BID), adalimumab (two RCTs), or placebo. pMDD/pGAD was defined as Short Form-36 Health Survey (SF-36) Mental Component Summary (MCS) score ≤ 38. Efficacy outcomes over 12 months included least squares mean change from baseline in SF-36 MCS score and Health Assessment Questionnaire-Disability Index, proportions of patients with pMDD/pGAD in those with baseline pMDD/pGAD, and American College of Rheumatology 20/50/70 response, and Disease Activity Score in 28 joints, erythrocyte sedimentation rate remission (< 2.6) rates. RESULTS: A total of 4404 patients with non-missing baseline values were included. Baseline pMDD/pGAD was reported by 44.5%, 39.8%, 45.4%, and 39.1% of patients receiving tofacitinib 5 mg BID, tofacitinib 10 mg BID, adalimumab, and placebo, respectively. SF-36 MCS improvements were greater for tofacitinib versus adalimumab/placebo through month 6, with numerical improvements for tofacitinib versus adalimumab sustained through month 12, when the proportions of patients with baseline pMDD/pGAD who continued to have pMDD/pGAD were reduced. RA efficacy outcomes were generally similar in patients with/without baseline pMDD/pGAD. CONCLUSIONS: The percentage of patients with pMDD/pGAD reduced from baseline over 1 year of treatment with tofacitinib or adalimumab. Effective treatment of underlying RA may lead to improvements in depression and anxiety, based on the SF-36 MCS. Specially designed studies using gold-standard diagnostic tools would be warranted to investigate this further. Video Abstract available for this article. TRIAL REGISTRATION: NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT02187055. Video Abstract (MP4 204475 KB).

Tofacitinib is a medicine used to treat rheumatoid arthritis (swollen and painful joints). A total of 4400 patients with moderate or severe rheumatoid arthritis who were taking part in tofacitinib clinical trials completed a survey about their general health and well-being at that time. We used their answers to determine whether they were likely to have depression or anxiety. We then looked at how common depression or anxiety was in patients with rheumatoid arthritis, and whether having depression or anxiety affected how patients responded to tofacitinib treatment. It is important to note that tofacitinib is not approved for the treatment of depression or anxiety, and these clinical trials were not designed to assess whether tofacitinib improved depression or anxiety symptoms. About 40% of patients likely had depression or anxiety when they started a clinical trial. This percentage decreased among patients who received tofacitinib treatment over a year. Patients treated with tofacitinib showed more improvement in their depression or anxiety than those treated with placebo. Over a year of treatment, tofacitinib improved signs and symptoms of rheumatoid arthritis, for example, the number of swollen or painful joints and fatigue. Having depression or anxiety did not change the way that patients responded to tofacitinib. This research shows how treating rheumatoid arthritis symptoms may also improve depression and anxiety symptoms. However, specially designed studies are needed to confirm this.

Humoral and T Cell Response to SARS-CoV-2 Vaccination in Patients With Rheumatoid Arthritis.

OBJECTIVE: The objective of this study was to assess the SARS-CoV-2-specific humoral and T cell response after a two-dose regimen of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA). METHODS: In this observational study, patients with RA who are ≥18 years of age and vaccinated for SARS-CoV-2 according to the Argentine National Health Ministry's vaccination strategy were included. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies (ELISA-COVIDAR test), neutralizing activity (cytotoxicity in VERO cells), and specific T cell response (IFN-γ ELISpot Assay) were assessed after the first and second dose. RESULTS: A total of 120 patients with RA were included. Mostly, homologous regimens were used, including Gam-COVID-Vac (27.5%), ChAdOx1 (24.2%), and BBIBP-CorV (22.5%). The most frequent combination was Gam-COVID-Vac/mRNA-1273 (21.7%). After the second dose, 81.7% presented with anti-SARS-CoV-2 antibodies, 70.0% presented with neutralizing activity, and 65.3% presented with specific T cell response. The use of BBIBP-CorV and treatment with abatacept (ABA) and rituximab (RTX) were associated with undetectable antibodies and no neutralizing activity after two doses. BBIBP-CorV was also associated with the absence of T cell response. The total incidence of adverse events was 357.1 events per 1,000 doses, significantly lower with BBIBP-CorV (166.7 events per 1,000 doses, P < 0.02). CONCLUSION: In this RA cohort vaccinated with homologous and heterologous regimens against COVID-19, 2 out of 10 patients did not develop anti-SARS-CoV-2 IgG, 70% presented with neutralizing activity, and 65% presented with specific T cell response. The use of BBIBP-CorV was associated with deficient humoral and cellular response, whereas treatment with ABA and RTX resulted in an impaired anti-SARS-CoV-2 IgG formation and neutralizing activity.

Hyposalivation and periodontal disease as oral non-articular characteristics in rheumatoid arthritis.

OBJECTIVE: To investigate the association among rheumatoid arthritis (RA), saliva production, and periodontal status. METHODS: An observational study was carried out on 103 subjects with RA and 103 without RA matched by sex and age. Rheumatologic evaluation included serological and clinical variables. A full mouth periodontal examination was performed according to the American Academy of Periodontology (1999). Resting and stimulated whole salivary flows were determined after spiting during 5 min. RESULTS: RA was associated with a higher prevalence of severe periodontitis (12% vs. 4%), with a marked reduction in resting and stimulated saliva production, and with a higher prevalence of resting (19% vs. 0%) and also stimulated hyposalivation (54% vs. 10%), compared with the control group. The differences in mean resting and stimulated salivary flows between RA and control groups persisted after the exclusion of people with hyposalivation. Saliva production was not associated with the presence or the severity of periodontal disease, or with the rheumatic clinical characteristics of the patients. CONCLUSIONS: More than 50% of people with RA have some degree of reduction in their salivary flows, an affection not associated with the periodontal status or rheumatic activity, which are the expression of the two related inflammatory diseases. The influence of autonomic dysfunction on hyposalivation can be considered. While periodontitis would be a disease-associated comorbidity of RA, poor saliva production should be included among the extra-articular manifestations. Key Points • Rheumatoid arthritis patients are more prone to suffer from periodontitis and/or hyposalivation. • Periodontal disease is more prevalent in people with rheumatoid arthritis and also an association was found between the severities of both pathologies. • More than 50% of people with RA would have some degree of reduction in their salivary flows, an affection not associated with the periodontal status or rheumatic activity. • Reduced saliva production in rheumatoid arthritis patients should be included among the extra-articular manifestations.

Reporte de pacientes con espondiloartritis y arteritis de Takayasu en Argentina: ¿asociación causal o casual? / Report of patients with spondyloarthritis and Takayasu's arteritis in Argentina: is it a causal or casual association?

Introducción: tanto las espondiloartritis (EspA) como la arteritis de Takayasu (TAK) son enfermedades infrecuentes y su asociación es aún más rara. Objetivos: presentar una serie de pacientes con diagnóstico concomitante de EspA o con rasgos de EspA y TAK en Argentina, y realizar una revisión de la literatura respecto de esta asociación. Materiales y métodos: se recopilaron las características demográficas, clínicas y terapéuticas de pacientes con diagnóstico concomitante de EspA o con algunos rasgos de EspA y TAK, de distintos centros de salud de la República Argentina. Resultados: se describen 7 pacientes, de los cuales 4 presentaban EspA, uno con compromiso axial (EspAax) juvenil, otro con artritis psoriásica (APs), otro con espondilitis anquilosante (EA) y el último con EspAax pura, y 3 de ellos tuvieron rasgos de EspA (enfermedad Crohn, psoriasis y oligoartritis asimétrica de grandes articulaciones). En la mayoría de los casos, los rasgos de EspA se presentaron con una mediana de 4 años antes de la TAK. Conclusiones: varios reportes y series de casos relatan la superposición entre estas dos enfermedades. Si bien las mismas podrían compartir cierta base genética común, todavía no contamos con evidencia sólida que permita estimar que esta asociación no es casual.

Introduction: both spondyloarthritis (SpA) and Takayasu arteritis (TAK) are rare diseases, and their association is even rarer. Objectives: to present a series of patients with a concomitant diagnosis of SpA or with features of SpA and TAK in Argentina and review the literature regarding this association. Materials and methods: the demographic, clinical and therapeutic characteristics of patients with a concomitant diagnosis of SpA or with some features of SpA and TAK were collected from different health centers in Argentina. Results: 7 patients are described, of which 4 had SpA, one with juvenile axial involvement (axSpA), another with psoriatic arthritis (PsA), another with ankylosing spondylitis (AS) and the last patient with pure axSpA and 3 of them had features of SpA (Crohn's disease, psoriasis and asymmetric oligoarthritis of large joints). In most cases, SpA features presented a median of 4 years before TAK. Conclusions: several case reports and case series reported overlap between these two diseases. Although they could share a certain common genetic basis, we still do not have solid evidence that allows us to estimate that this association is not coincidental.

Pan American League of Associations for Rheumatology recommendations for the management of axial spondyloarthritis.

Axial spondyloarthritis (axSpA) comprises a spectrum of chronic inflammatory manifestations affecting the axial skeleton and represents a challenge for diagnosis and treatment. Our objective was to generate a set of evidence-based recommendations for the management of axSpA for physicians, health professionals, rheumatologists and policy decision makers in Pan American League of Associations for Rheumatology (PANLAR) countries. Grading of Recommendations, Assessment, Development and Evaluation-ADOLOPMENT methodology was used to adapt existing recommendations after performing an independent systematic search and synthesis of the literature to update the evidence. A working group consisting of rheumatologists, epidemiologists and patient representatives from countries within the Americas prioritized 13 topics relevant to the context of these countries for the management of axSpA. This Evidence-Based Guideline article reports 13 recommendations addressing therapeutic targets, the use of NSAIDs and glucocorticoids, treatment with DMARDs (including conventional synthetic, biologic and targeted synthetic DMARDs), therapeutic failure, optimization of the use of biologic DMARDs, the use of drugs for extra-musculoskeletal manifestations of axSpA, non-pharmacological interventions and the follow-up of patients with axSpA.

Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis.

BACKGROUND: Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents. METHODS: We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response. RESULTS: The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab. CONCLUSION: We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.

The trajectory of clinical responses in patients with early rheumatoid arthritis who achieve sustained remission in response to abatacept: subanalysis of AVERT-2, a randomized phase IIIb study.

BACKGROUND: AVERT-2 (a phase IIIb, two-stage study) evaluated abatacept + methotrexate versus methotrexate alone, in methotrexate-naive, anti-citrullinated protein antibody-positive patients with early (≤ 6 months), active RA. This subanalysis investigated whether individual patients who achieved the week 24 Simplified Disease Activity Index (SDAI) remission primary endpoint could sustain remission to 1 year and then maintain it following changes in therapy. METHODS: During the 56-week induction period (IP), patients were randomized to weekly subcutaneous abatacept 125 mg + methotrexate or abatacept placebo + methotrexate. Patients completing the IP who achieved SDAI remission (≤ 3.3) at weeks 40 and 52 entered a 48-week de-escalation (DE) period. Patients treated with abatacept + methotrexate were re-randomized to continue weekly abatacept + methotrexate, or de-escalate and then withdraw abatacept (after 24 weeks), or receive abatacept monotherapy. Proportions of patients achieving sustained SDAI and Boolean remission, and Disease Activity Score in 28 joints using C-reactive protein (DAS28 [CRP]) < 2.6, were assessed. For patients achieving early sustained SDAI remission at weeks 24/40/52, flow between disease activity categories and individual trajectories was evaluated; flow was also evaluated for later remitters (weeks 40/52 but not week 24). RESULTS: Among patients treated with abatacept + methotrexate (n/N = 451/752) at IP week 24, 22% achieved SDAI remission, 17% achieved Boolean remission, and 42% achieved DAS28 (CRP) < 2.6; of these, 56%, 58%, and 74%, respectively, sustained a response throughout IP weeks 40/52. Among patients with a sustained response at IP weeks 24/40/52, 82% (14/17) on weekly abatacept + methotrexate, 81% (13/16) on abatacept monotherapy, 63% (12/19) who de-escalated/withdrew abatacept, and 65% (11/17) on abatacept placebo + methotrexate were in SDAI remission at end of the DE period; rates were higher than for later remitters in all arms except abatacept placebo + methotrexate. CONCLUSIONS: A high proportion of individual patients achieving clinical endpoints at IP week 24 with abatacept + methotrexate sustained their responses through week 52. Of patients achieving early and sustained SDAI remission through 52 weeks, numerically more maintained remission during the DE period if weekly abatacept treatment continued. TRIAL REGISTRATION: NCT02504268 (ClinicalTrials.gov), registered July 21, 2015.

Sustained Remission and Outcomes with Abatacept plus Methotrexate Following Stepwise Dose De-escalation in Patients with Early Rheumatoid Arthritis.

INTRODUCTION: One target of rheumatoid arthritis (RA) treatment is to achieve early sustained remission; over the long term, patients in sustained remission have less structural joint damage and physical disability. We evaluated Simplified Disease Activity Index (SDAI) remission with abatacept + methotrexate versus abatacept placebo + methotrexate and impact of de-escalation (DE) in anti-citrullinated protein antibody (ACPA)-positive patients with early RA. METHODS: The phase IIIb, randomized, AVERT-2 two-stage study (NCT02504268) evaluated weekly abatacept + methotrexate versus abatacept placebo + methotrexate. PRIMARY ENDPOINT: SDAI remission (≤ 3.3) at week 24. Pre-planned exploratory endpoint: maintenance of remission in patients with sustained remission (weeks 40 and 52) who, from week 56 for 48 weeks (DE period), (1) continued combination abatacept + methotrexate, (2) tapered abatacept to every other week (EOW) + methotrexate for 24 weeks with subsequent abatacept withdrawal (abatacept placebo + methotrexate), or (3) withdrew methotrexate (abatacept monotherapy). RESULTS: Primary study endpoint was not met: 21.3% (48/225) of patients in the combination and 16.0% (24/150) in the abatacept placebo + methotrexate arm achieved SDAI remission at week 24 (p = 0.2359). There were numerical differences favoring combination therapy in clinical assessments, patient-reported outcomes (PROs) and week 52 radiographic non-progression. After week 56, 147 patients in sustained remission with abatacept + methotrexate were randomized (combination, n = 50; DE/withdrawal, n = 50; abatacept monotherapy, n = 47) and entered DE. At DE week 48, SDAI remission (74%) and PRO improvements were mostly maintained with continued combination therapy; lower remission rates were observed with abatacept placebo + methotrexate (48.0%) and with abatacept monotherapy (57.4%). Before withdrawal, de-escalating to abatacept EOW + methotrexate preserved remission. CONCLUSIONS: The stringent primary endpoint was not met. However, in patients achieving sustained SDAI remission, numerically more maintained remission with continued abatacept + methotrexate versus abatacept monotherapy or withdrawal. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02504268. Video abstract (MP4 62241 KB).

Patients with rheumatoid arthritis (RA) experience inflamed and damaged joints. RA is an autoimmune disease in which proteins called autoantibodies, particularly anti-citrullinated protein autoantibodies, target the patient's own joint tissue and organs by mistake, leading to symptomatic inflammation. Successful treatment can decrease the disease's activity to a state known as remission. Patients in remission may experience little or no symptoms and it may be possible for some to then be able to decrease their treatment. Here, we report the results of a large, international study that looked at two treatments, abatacept and methotrexate, in patients with RA and anti-citrullinated protein autoantibodies. The study had two parts. Firstly, to see how many patients had success (remission) with weekly abatacept and/or methotrexate treatment, and secondly, to see if remission was maintained when treatment was either continued or decreased and stopped. The study showed that the number of patients in remission 6 months after treatment started was not greatly different between patients treated with both abatacept and methotrexate and those treated with just methotrexate. Those taking abatacept and methotrexate together had better remission rates 1 year later. More patients also stayed in remission when they continued to receive both abatacept and methotrexate compared with those who were just treated with abatacept or when their abatacept treatment was decreased and stopped. More patients stayed in remission when abatacept was decreased than when it was stopped. The results from this study may help determine possible future treatment reduction and/or withdrawal plans for some patients with RA.

Seguridad de las drogas biológicas y sintéticas dirigidas utilizadas en pacientes con enfermedades reumáticas inmunomediadas. Datos del registro BIOBADASAR 3.0 / Safety of biological and targeted synthetic drugs in patients with immune-mediated rheumatic diseases. Data from the BIOBADASAR 3.0 registry

Introducción: conocer la seguridad de las drogas actualmente disponibles para el tratamiento de las enfermedades reumáticas es muy importante al momento de tomar decisiones terapéuticas objetivas e individualizadas en la consulta médica diaria. Asimismo, datos de la vida real amplían el conocimiento revelado por los ensayos clínicos. Objetivos: describir los eventos adversos (EA) reportados, estimar su frecuencia e identificar los factores relacionados con su desarrollo. Materiales y métodos: se utilizaron datos BIOBADASAR, un registro voluntario y prospectivo de seguimiento de EA de tratamientos biológicos y sintéticos dirigidos en pacientes con enfermedades reumáticas inmunomediadas. Los pacientes son seguidos hasta la muerte, pérdida de seguimiento o retiro del consentimiento informado. Para este análisis se extrajeron datos recopilados hasta el 31 de enero de 2023. Resultados: se incluyó un total de 6253 pacientes, los cuales aportaron 9533 ciclos de tratamiento, incluyendo 3647 (38,3%) ciclos sin drogas modificadoras de la enfermedad biológicas y sintéticas dirigidas (DME-b/sd) y 5886 (61,7%) con DME-b/sd. Dentro de estos últimos, los más utilizados fueron los inhibidores de TNF y abatacept. Se reportaron 5890 EA en un total de 2701 tratamientos (844 y 1857 sin y con DME-b/sd, respectivamente), con una incidencia de 53,9 eventos cada 1000 pacientes/año (IC 95% 51,9-55,9). La misma fue mayor en los ciclos con DME-b/sd (71,1 eventos cada 1000 pacientes/año, IC 95% 70,7-77,5 versus 33,7, IC 95% 31,5-36,1; p<0,001). Las infecciones, particularmente las de la vía aérea superior, fueron los EA más frecuentes en ambos grupos. El 10,9% fue serio y el 1,1% provocó la muerte del paciente. El 18,7% de los ciclos con DME-b/sd fue discontinuado a causa de un EA significativamente mayor a lo reportado en el otro grupo (11,5%; p<0,001). En el análisis ajustado, las DME-b/sd se asociaron a mayor riesgo de presentar al menos un EA (HR 1,82, IC 95% 1,64-1,96). De igual manera, la mayor edad, el mayor tiempo de evolución, el antecedente de enfermedad pulmonar obstructiva crónica, el diagnóstico de lupus eritematoso sistémico y el uso de corticoides se asociaron a mayor riesgo de EA. Conclusiones: la incidencia de EA fue significativamente superior durante los ciclos de tratamientos que incluían DME-b/sd.

Introduction: knowing the efficacy and safety of the drugs currently available for the treatment of rheumatic diseases is very important when making objective and individualized therapeutic decisions in daily medical consultation. Likewise, real-life data extends the knowledge revealed by clinical trials. Objectives: to describe the reported adverse events (AEs), estimate their frequency and identify factors associated to them. Materials and methods: BIOBADASAR data were used, which is a voluntary, prospective follow-up registry of AEs of biological and synthetic treatments in patients with immune-mediated rheumatic diseases. Patients are followed until death, loss of followup, or withdrawal of informed consent. To carry out this analysis, the data collected up to January 31, 2023 was extracted. Results: a total of 6253 patients were included, who contributed with 9533 treatment periods, including 3647 (38.3%) periods without b/ts-DMARDs and 5886 (61.7%) with b/ts-DMARDs. Among the latter, the most used were TNF inhibitors and abatacept. A total of 5890 AEs were reported in a total of 2701 treatments (844 and 1857 without and with b/ts-DMARDs, respectively), with an incidence of 53.9 events per 1000 patients/ year (95% CI 51.9-55.9). It was higher during the periods with b/ts-DMARDs (71.1 events per 1000 patients/year, 95% CI 70.7-77.5 vs 33.7, 95% CI 31.5-36.1, p<0.001). Infections, particularly those of the upper respiratory tract, were the most frequent AEs in both groups. 10.9% were severe and 1.1% were associated with the death of the patient. 18.7% of the periods with b/ts-DMARDs were discontinued due to an AE, significantly higher than that reported in the other group (11.5%; p<0.001). In the adjusted analysis, b/ts-DMARDs were associated with a higher risk of presenting at least one AE (HR 1.82, 95% CI 1.64-1.96). Similarly, older age, longer evolution time, history of chronic obstructive pulmonary disease, diagnosis of systemic lupus erythematosus, and use of corticosteroids were associated with a higher risk of AE. Conclusions: the incidence of AEs was significantly higher during those treatment periods that included DME-b/sd.

Comparison of disease activity index for psoriatic arthritis (DAPSA) and minimal disease activity (MDA) targets for patients with psoriatic arthritis: A post hoc analysis of data from phase 3 tofacitinib studies.

OBJECTIVE: To compare achievement of Disease Activity Index in Psoriatic Arthritis (DAPSA) remission (REM)/low disease activity (LDA) with very low disease activity (VLDA)/minimal disease activity (MDA) targets in tofacitinib-treated patients with psoriatic arthritis (PsA). METHODS: In this post hoc analysis, data were pooled from two phase 3 studies (6 months' [NCT01882439] and 12 months' [NCT01877668] duration) of patients with PsA receiving tofacitinib 5 or 10 mg twice daily. Cut-offs for DAPSA targets: ≤4 for clinical REM and >4-≤14 for LDA. VLDA and MDA were defined as meeting 7 or ≥5, respectively, of 7 criteria. An ordered logistic regression model was performed to evaluate associations between baseline characteristics and achievement of DAPSA targets as well as VLDA/MDA at month 3. Agreement between achieving DAPSA and VLDA/MDA targets at months 1-6 was assessed via kappa tests. Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) scores (month 6), modified Total Sharp Score (mTSS) and proportion of radiographic non-progressors (mTSS ≤0.5) at month 12 (NCT01877668 only) were compared across DAPSA and VLDA/MDA targets. RESULTS: Increased disease activity at baseline was associated with reduced likelihood of achieving DAPSA-REM/DAPSA-LDA or VLDA/MDA at month 3. There was moderate agreement (kappa values 0.41-0.60) between DAPSA-REM and VLDA, and DAPSA-LDA and MDA, from months 1 to 6, although over half of patients achieving DAPSA-REM and over two thirds of patients achieving DAPSA-LDA, respectively, were not captured by VLDA and MDA. Achieving DAPSA-REM/DAPSA-LDA or VLDA/MDA was associated with improved HAQ-DI and SF-36 PCS scores at month 6, and slightly reduced radiographic progression at month 12. CONCLUSION: This analysis of data from tofacitinib-treated patients with PsA demonstrated moderate agreement between the DAPSA and VLDA/MDA composite instruments. In agreement with previous studies, VLDA and MDA may be more difficult to achieve than DAPSA-REM and DAPSA-LDA, respectively. However, the clinical and prognostic relevance of this finding should be determined. These data support DAPSA and VLDA/MDA as useful tools for evaluating disease activity and treatment response in PsA. CLINICALTRIALS: GOV: NCT01882439; NCT01877668.

Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis

Abstract Background Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents. Methods We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response. Results The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab. Conclusion We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab. Key messages Abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.

Immune Response to SARS-CoV-2 Third Vaccine in Patients With Rheumatoid Arthritis Who Had No Seroconversion After Primary 2-Dose Regimen With Inactivated or Vector-Based Vaccines.

OBJECTIVE: The aim of this study was to assess the immune response after a third dose of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA) with undetectable antibody titers after the primary regimen of 2 doses. METHODS: Patients with RA with no seroconversion after 2 doses of SARS-CoV-2 vaccine and who received a third dose of either an mRNA or vector-based vaccine were included. Anti-SARS-CoV-2 IgG antibodies, neutralizing activity, and T cell responses were assessed after the third dose. RESULTS: A total of 21 nonresponder patients were included. At the time of vaccination, 29% were receiving glucocorticoids and 85% biologic disease-modifying antirheumatic drugs (including 6 taking abatacept [ABA] and 4 taking rituximab [RTX]). The majority (95%) received the BNT162b2 vaccine and only one of them received the ChAdOx1 nCoV-19 vaccine. After the third dose, 91% of the patients presented detectable anti-SARS-CoV-2 IgG and 76% showed neutralizing activity. Compared to other treatments, ABA and RTX were associated with the absence of neutralizing activity in 4 out of 5 (80%) patients and lower titers of neutralizing antibodies (median 3, IQR 0-20 vs 8, IQR 4-128; P = 0.20). Specific T cell response was detected in 41% of all patients after the second dose, increasing to 71% after the third dose. The use of ABA was associated with a lower frequency of T cell response (33% vs 87%, P = 0.03). CONCLUSION: In this RA cohort, 91% of patients who failed to seroconvert after 2 doses of SARS-CoV-2 vaccine presented detectable anti-SARS-CoV-2 IgG after a third dose. The use of ABA was associated with a lower frequency of specific T cell response.

Frecuencia de comorbilidades en pacientes con artritis psoriásica y evaluación de la adherencia de los médicos a las recomendaciones de tratamiento de las Guías GRAPPA 2015 / Frequency of comorbidities in patients with psoriatic arthritis and evaluation of the adherence of physicians to the treatment recommendations of the GRAPPA 2015 Guidelines

Introducción: los pacientes con artritis psoriásica (APs) presentan más comorbilidades. Las guías del Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) establecen lineamientos para los tratamientos de acuerdo a ellas. Objetivos: describir la prevalencia de comorbilidades en pacientes con APs según el Rheumatic Disease Comorbidity Index (RDCI), analizar el efecto sobre la enfermedad y estudiar la adherencia a las guías GRAPPA. Materiales y métodos: estudio observacional. Se incluyeron pacientes con APs de la cohorte RAPSODIA. Se reportaron características sociodemográficas y clínicas. Las comorbilidades se valoraron por RDCI. Se estudiaron variables asociadas a RDCI ≥1 mediante análisis multivariado. Se analizó el cumplimiento de las recomendaciones de tratamiento en relación a las comorbilidades según las guías GRAPPA. Resultados: se incluyeron 170 pacientes. El 67,6% presentó al menos una comorbilidad (RDCI ≥1); estos eran de mayor edad (X 57,3±12,7 años vs. 48,2±13,2 años; p<0,0001), presentaban más sobrepeso u obesidad (84,3% vs. 67,3%; p=0,011) y peor calidad de vida (PsAQoL X 7,6±6,6 vs. 5,2±6; p=0,025). El análisis multivariado evidenció asociación de la edad y el uso de antiinflamatorios no esteroideos (AINEs) con RDCI ≥1. Contrariamente a las recomendaciones de GRAPPA, el 70% de los pacientes con cardiopatía utilizaba AINEs, y la mitad de aquellos con enfermedades hepáticas o renales tomaba AINEs o metotrexato. Conclusiones: la prevalencia de comorbilidades en los pacientes con APs es alta. En algunos casos no se cumplían las recomendaciones de tratamiento en relación a las comorbilidades.

Introduction: comorbidities are common in patients with psoriatic arthritis (PsA). The GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) guidelines strengthen the choice of treatments according to them. Objetives: to describe the prevalence of comorbidities in patients with psoriatic arthritis according to Rheumatic Disease Comorbidity Index (RDCI) and to analyze the influence of them on disease activity, functional capacity and quality life and to assess adherence to GRAPPA 2015 treatment recommendations according to the presence of comorbidities. Materials and methods: adult patients with PsA (CASPAR criteria) from the RAPSODIA cohort were included. Sociodemographic and clinical characteristics, disease activity and current treatment were recorded. Comorbidities were assessed by the RDCI. Variables associated with RDCI≥1 were studied by multivariate analysis. Adherence to treatment recommendations in relation to the reported comorbidities was analyzed according to the 2015 GRAPPA guidelines. Results: a total of 170 patients were included. Patients with RDCI ≥1 were reported by 67.6%. These patients were older (57±13 years vs 48±13 years, p<0.0001), had a higher frequency of overweight or obesity (84.3% vs 67.3%, p=0.011), and had a poorer quality of life (PsAQoL 7.6±6.6 vs 5.2±6, p=0.025). The multivariate analysis showed an association between age and the use of NSAIDs with RDCI≥1. Contrary to GRAPPA recommendations, 70% of patients with heart disease were using NSAIDs. Moreover, about half of those with hepatic or kidney disease took NSAIDs or methotrexate. Conclusions: most patients with PsA presented at least one comorbidity. GRAPPA recommendations were not followed in a considerable number of patients.

Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials.

INTRODUCTION: The Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported outcome tool recommended for the assessment of disease activity in patients with rheumatoid arthritis (RA) in clinical practice. This analysis evaluated the long-term effect of upadacitinib vs. comparators on RAPID3 scores in patients with RA in the phase 3 SELECT clinical trial program. METHODS: This post hoc analysis included data from five randomized controlled trials (RCTs) in patients receiving upadacitinib 15 mg or 30 mg once daily (QD) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The proportions of patients reporting RAPID3 remission (scores ≤ 3) were assessed at week 60. Correlations between absolute scores for RAPID3 and Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and 28-joint Disease Activity Score with C-reactive protein (DAS28[CRP]) at week 60 were assessed using Spearman correlation coefficients. RESULTS: A total of 3117 patients were included from the SELECT-NEXT, -BEYOND, -MONOTHERAPY, -COMPARE, and -EARLY trials. By week 60, 32-52% of methotrexate-naïve and csDMARD inadequate responder (IR) patients treated with either upadacitinib 15 mg QD or upadacitinib 30 mg QD reported RAPID3 scores consistent with remission. The proportions were slightly lower in the biologic DMARD-IR SELECT-BEYOND population (19-28%). RAPID3 scores highly correlated (Spearman correlation values ≥ 0.58) with CDAI, SDAI, and DAS28(CRP) scores through week 60 (all p < 0.001). CONCLUSIONS: Upadacitinib, as monotherapy or in combination with csDMARDs, was associated with patient-reported remission assessed by RAPID3 over 60 weeks across the SELECT RCTs in patients with RA. TRIAL REGISTRATION: SELECT-BEYOND (NCT02706847); SELECT-NEXT (NCT02675426); SELECT-MONOTHERAPY (NCT02706951); SELECT-EARLY (NCT02706873); SELECT-COMPARE (NCT02629159).

Rheumatoid arthritis (RA) is a disease that causes inflammation of the joints. Doctors have several ways of assessing how bad a patient's disease is, and these often use a combination of signs and symptoms to develop a 'score'. One method is called RAPID3, which is a score based on an overall assessment of the disease by the patient, the level of pain, and the amount of physical disability. An advantage of RAPID3 is that it is quick and easy to use, and since it uses only patient-reported symptoms, it can be measured easily via telemedicine, without the need for an in-person consultation. In this study, we decided to look into the effect of upadacitinib, a drug used for the treatment of RA, on RAPID3 score in patients with RA. We also investigated whether RAPID3 correlates with other ways of measuring RA severity, including scores that use physician-measured factors such as number of affected joints, as this can help show whether RAPID3 is a valid and useful tool. We found that upadacitinib led to long-term improvements in RAPID3 score, and that results were the same in different studies and patient groups, including patients who had not responded well to other treatments. We also found that RAPID3 correlated well with other measures, i.e., improvements in RAPID3 happened in parallel with improvements in other scores. Overall, these results suggest that RAPID3 can be a useful tool in patients with RA.

Infections in patients with rheumatoid arthritis receiving tofacitinib versus tumour necrosis factor inhibitors: results from the open-label, randomised controlled ORAL Surveillance trial.

OBJECTIVES: To characterise infections in patients with rheumatoid arthritis (RA) in ORAL Surveillance. METHODS: In this open-label, randomised controlled trial, patients with RA aged≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg two times per day or a tumour necrosis factor inhibitor (TNFi). Incidence rates (IRs; patients with first events/100 patient-years) and hazard ratios (HRs) were calculated for infections, overall and by age (50-<65 years; ≥65 years). Probabilities of infections were obtained (Kaplan-Meier estimates). Cox modelling identified infection risk factors. RESULTS: IRs/HRs for all infections, serious infection events (SIEs) and non-serious infections (NSIs) were higher with tofacitinib (10>5 mg two times per day) versus TNFi. For SIEs, HR (95% CI) for tofacitinib 5 and 10 mg two times per day versus TNFi, respectively, were 1.17 (0.92 to 1.50) and 1.48 (1.17 to 1.87). Increased IRs/HRs for all infections and SIEs with tofacitinib 10 mg two times per day versus TNFi were more pronounced in patients aged≥65 vs 50-<65 years. SIE probability increased from month 18 and before month 6 with tofacitinib 5 and 10 mg two times per day versus TNFi, respectively. NSI probability increased before month 6 with both tofacitinib doses versus TNFi. Across treatments, the most predictive risk factors for SIEs were increasing age, baseline opioid use, history of chronic lung disease and time-dependent oral corticosteroid use, and, for NSIs, female sex, history of chronic lung disease/infections, past smoking and time-dependent Disease Activity Score in 28 joints, C-reactive protein. CONCLUSIONS: Infections were higher with tofacitinib versus TNFi. Findings may inform future treatment decisions. TRIAL REGISTRATION NUMBER: NCT02092467.

Simplified Ankylosing Spondylitis Disease Activity Score (SASDAS) Versus ASDAS: A Post Hoc Analysis of a Randomized Controlled Trial.

OBJECTIVE: To compare the Simplified Ankylosing Spondylitis Disease Activity Score (SASDAS) against the Ankylosing Spondylitis Disease Activity Score (ASDAS) for measuring and categorizing disease activity using data from the EMBARK trial (ClinicalTrials.gov: NCT01258738), a randomized controlled trial of etanercept (ETN) for axial spondyloarthritis (axSpA). METHODS: Patients with early active axSpA received ETN 50 mg once weekly (n = 106) or placebo (PBO; n = 109) for 12 weeks in a double-blind manner; they then received open-label ETN for 92 weeks. For this analysis, ASDAS-C-reactive protein (CRP) and SASDAS-CRP were calculated at baseline, week 12, and week 24. The SASDAS was calculated by the linear addition of the ASDAS components without adjustment. RESULTS: A very strong correlation, as determined by the Spearman correlation coefficient, was observed between the ASDAS and SASDAS for continuous variables at baseline and during treatment. For pooled categorical data at baseline, the SASDAS placed 69.9% of patients in the same disease categories as the ASDAS but overestimated for 17.8% of patients and underestimated for 12.2% of patients. A similar pattern was seen postbaseline. Cohen weighted [Formula: see text] statistics for all individual and pooled treatments and timepoints (0.54-0.73) reflected moderate to substantial agreement. The capacity to differentiate between treatments (ie, ETN and PBO/ETN) was higher with the ASDAS (effect size -0.74, 95% CI -1.03 to -0.46) compared with the SASDAS (effect size -0.51, 95% CI -0.79 to -0.23), but sensitivity to change was generally similar. CONCLUSION: A very strong correlation between the SASDAS and ASDAS was observed when considering continuous variables; however, moderate to substantial agreement was observed for categorical data, and the SASDAS classified a lower proportion of patients as being in the inactive and low disease activity categories.