Factors Associated With Mortality in Patients With Immune-Mediated Rheumatic Diseases and COVID-19 From Latin America: Data From Argentina, Mexico, and Brazil.

OBJECTIVE: To describe characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) from Argentina, Mexico and Brazil, and to assess factors associated with mortality in this population. METHODS: Data from 3 national registries, SAR-COVID (Argentina), CMR-COVID (Mexico), and ReumaCoV-Brasil (Brazil), were combined. Adult patients with IMIDs and SARS-CoV-2 infection were recruited. Sociodemographic data, comorbidities, IMID clinical characteristics and treatment, and SARS-CoV-2 infection presentation and outcomes were recorded. RESULTS: A total of 4827 individuals were included: 2542 (52.7%) from SAR-COVID, 1167 (24.2%) from CMR-COVID, and 1118 (23.1%) from ReumaCoV-Brasil. Overall, 82.1% were female with a mean age of 49.7 (SD, 14.3) years; 22.7% of the patients were hospitalized, and 5.3% died because of COVID-19 (coronavirus disease 2019). Argentina and Brazil had both 4% of mortality and Mexico 9.4%. In the multivariable analysis, older age (≥60 years; odds ratio [OR], 7.4; 95% confidence interval [CI], 4.6-12.4), male sex (OR, 1.5; 95% CI, 1.1-2.1), living in Mexico (OR, 3.0; 95% CI, 2.0-4.4), comorbidity count (1 comorbidity: OR, 1.5; 95% CI, 1.0-2.1), diagnosis of connective tissue disease or vasculitis (OR, 1.8; 95% CI, 1.3-2.4), and other diseases (OR, 2.6; 95% CI, 1.6-4.1) compared with inflammatory joint disease, high disease activity (OR, 4.2; 95% CI, 2.5-7.0), and treatment with glucocorticoids (OR, 1.9; 95% CI, 1.4-2.5) or rituximab (OR, 4.2; 95% CI, 2.7-6.6) were associated with mortality. CONCLUSIONS: Mortality in patients with IMIDs was particularly high in Mexicans. Ethnic, environmental, societal factors, and different COVID-19 mitigation measures adopted have probably influenced these results.

Vacunación contra influenza y neumococo en pacientes con artritis reumatoide / Vaccination against influenza and pneumococus in patients with rheumatoid arthritis

Antecedentes: La vacunación contra agentes infecciosos como influenza y neumococo está ampliamente recomendada para pacientes con artritis reumatoide, no se conoce la prevalencia de adherencia a estos programas de vacunación en México. Métodos: Se realizó un estudio descriptivo trasversal, por medio de aplicación de encuesta a pacientes adultos con diagnóstico de artritis reumatoide atendidos en un hospital de tercer nivel en la Ciudad de México. Resultados: Se incluyeron 227 pacientes, se encontró una prevalencia de vacunación contra influenza en 31,3% y contra neumococo en 17,6% de los pacientes, los principales motivos para el no cumplimiento del esquema de vacunación estuvieron en relación con el desconocimiento y a la recomendación por parte de los médicos de no hacerlo. Conclusiones: El cumplimiento de los esquemas de vacunación recomendados en la población estudiada es más bajo que los reportados en otras poblaciones. Las intervenciones más importantes para mejorar la cobertura deben ir encaminadas a la educación tanto de pacientes, como de personal médico.(AU)

Background: Vaccination against pathogens such as influenza or pneumococcus is widely recommended for patients with rheumatoid arthritis; the prevalence of adherence to these vaccination programmes in Mexico is not known. Methods: A cross-sectional descriptive study was carried out, through the application of a survey to adult patients with a diagnosis of rheumatoid arthritis treated in a tertiary hospital in Mexico City. Results: 227 patients were included, vaccination against influenza was found in 31.3% and against pneumococcus in 17.6% of patients, the main reasons for non-compliance with the vaccination schedule were related to ignorance and the recommendation by doctors not to do so. Conclusions: Compliance with the recommended vaccination schedules in the studied population is lower than those reported in other populations. The most important interventions to improve coverage should be aimed at educating both patients and medical personnel.(AU)

Vaccination against influenza and pneumococus in patients with rheumatoid arthritis.

BACKGROUND: Vaccination against pathogens such as influenza or pneumococcus is widely recommended for patients with rheumatoid arthritis; the prevalence of adherence to these vaccination programmes in Mexico is not known. METHODS: A cross-sectional descriptive study was carried out, through the application of a survey to adult patients with a diagnosis of rheumatoid arthritis treated in a tertiary hospital in Mexico City. RESULTS: 227 patients were included, vaccination against influenza was found in 31.3% and against pneumococcus in 17.6% of patients, the main reasons for non-compliance with the vaccination schedule were related to ignorance and the recommendation by doctors not to do so. CONCLUSIONS: Compliance with the recommended vaccination schedules in the studied population is lower than those reported in other populations. The most important interventions to improve coverage should be aimed at educating both patients and medical personnel.

Biological impact of iberdomide in patients with active systemic lupus erythematosus.

OBJECTIVES: Iberdomide is a high-affinity cereblon ligand that promotes proteasomal degradation of transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). Pharmacodynamics and pharmacokinetics of oral iberdomide were evaluated in a phase 2b study of patients with active systemic lupus erythematosus (SLE). METHODS: Adults with autoantibody-positive SLE were randomised to placebo (n=83) or once daily iberdomide 0.15 mg (n=42), 0.3 mg (n=82) or 0.45 mg (n=81). Pharmacodynamic changes in whole blood leucocytes were measured by flow cytometry, regulatory T cells (Tregs) by epigenetic assay, plasma cytokines by ultrasensitive cytokine assay and gene expression by Modular Immune Profiling. RESULTS: Iberdomide exhibited linear pharmacokinetics and dose-dependently modulated leucocytes and cytokines. Compared with placebo at week 24, iberdomide 0.45 mg significantly (p<0.001) reduced B cells, including those expressing CD268 (TNFRSF13C) (-58.3%), and plasmacytoid dendritic cells (-73.9%), and increased Tregs (+104.9%) and interleukin 2 (IL-2) (+144.1%). Clinical efficacy was previously reported in patients with high IKZF3 expression and high type I interferon (IFN) signature at baseline and confirmed here in those with an especially high IFN signature. Iberdomide decreased the type I IFN gene signature only in patients with high expression at baseline (-81.5%; p<0.001) but decreased other gene signatures in all patients. CONCLUSION: Iberdomide significantly reduced activity of type I IFN and B cell pathways, and increased IL-2 and Tregs, suggesting a selective rebalancing of immune abnormalities in SLE. Clinical efficacy corresponded to reduction of the type I IFN gene signature. TRIAL REGISTRATION NUMBER: NCT03161483.

Phase 2 Trial of Iberdomide in Systemic Lupus Erythematosus.

BACKGROUND: Iberdomide, a cereblon modulator promoting degradation of the transcription factors Ikaros and Aiolos, which affect leukocyte development and autoimmunity, is being evaluated for the treatment of systemic lupus erythematosus (SLE). METHODS: In this phase 2 trial, we randomly assigned patients in a 2:2:1:2 ratio to receive oral iberdomide (at a dose of 0.45, 0.30, or 0.15 mg) or placebo once daily for 24 weeks, in addition to standard medications. The primary end point at week 24 was a response on the SLE Responder Index (SRI-4), which was defined as a reduction of at least 4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 score (a 24-item weighted score of lupus activity that ranges from 0 to 105, with higher scores indicating greater disease activity), no new disease activity as measured on the British Isles Lupus Assessment Group 2004 index, and no increase of 0.3 points or more in the Physician's Global Assessment score (on a visual-analogue scale ranging from 0 [no disease activity] to 3 [maximal disease]). RESULTS: A total of 288 patients received the assigned intervention: 81 received iberdomide at a dose of 0.45 mg, 82 received iberdomide at a dose of 0.30 mg, 42 received iberdomide at a dose of 0.15 mg, and 83 received placebo. At week 24, the percentages of patients with an SRI-4 response were 54% in the iberdomide 0.45-mg group, 40% in the iberdomide 0.30-mg group, 48% in the iberdomide 0.15-mg group, and 35% in the placebo group (adjusted difference between the iberdomide 0.45-mg group and the placebo group, 19.4 percentage points; 95% confidence interval, 4.1 to 33.4; P = 0.01), with no significant differences between the groups that received the lower doses of iberdomide and the group that received placebo. Iberdomide-associated adverse events included urinary tract and upper respiratory tract infections and neutropenia. CONCLUSIONS: In this 24-week, phase 2 trial involving patients with SLE, iberdomide at a dose of 0.45 mg resulted in a higher percentage of patients with an SRI-4 response than did placebo. Data from larger, longer trials are needed to determine the efficacy and safety of iberdomide in SLE. (Funded by Bristol Myers Squibb; ClinicalTrials.gov number, NCT03161483; EudraCT number, 2016-004574-17.).

Update of the Mexican College of Rheumatology Guidelines for the Pharmacological Treatment of Rheumatoid Arthritis, 2018. / Actualización de las guías del tratamiento farmacológico de la artritis reumatoide del Colegio Mexicano de Reumatología 2018.

Therapeutic advances in rheumatoid arthritis require periodic review of treatment guidelines. OBJECTIVE: To update the Mexican College of Rheumatology guidelines on the pharmacological treatment of rheumatoid arthritis. METHOD: Board certified rheumatologists from different health institutions and regions of the country participated. Work teams were formed that reviewed the previous guidelines, elaborated new questions, reviewed the literature, and scored the evidence that was presented and discussed in plenary session. The conclusions were presented to infectologists, gynaecologists and patients. Recommendations were based on levels of evidence according to GRADE methodology. RESULTS: Updated recommendations on the use of available medications for rheumatoid arthritis treatment in Mexico up to 2017 are presented. The importance of adequate and sustained control of the disease is emphasized and relevant safety aspects are described. Bioethical conflicts are included, and government action is invited to strengthen correct treatment of the disease. CONCLUSIONS: The updated recommendations of the Mexican College of Rheumatology on the pharmacological treatment of rheumatoid arthritis incorporate the best available information to be used in the Mexican health care system.

Efficacy and safety of switching from rituximab to biosimilar CT-P10 in rheumatoid arthritis: 72-week data from a randomized Phase 3 trial.

OBJECTIVE: To evaluate the efficacy and safety of CT-P10, a rituximab biosimilar after a single switch, during a multinational, randomized, double-blind Phase 3 trial involving patients with RA. METHODS: Patients received 48 weeks' treatment with CT-P10 or United States- or European Union-sourced reference rituximab (US-RTX and EU-RTX, respectively). Patients entering the extension period (weeks 48-72) remained on CT-P10 (CT-P10/CT-P10; n = 122) or US-RTX (US-RTX/US-RTX; n = 64), or switched to CT-P10 from US-RTX (US-RTX/CT-P10; n = 62) or EU-RTX (EU-RTX/CT-P10; n = 47) for an additional course. Efficacy endpoints included Disease Activity Score using 28 joints (DAS28), American College of Rheumatology (ACR) response rates, and quality of life-related parameters. Pharmacodynamics, immunogenicity and safety were also assessed. RESULTS: At week 72, similar improvements were observed by disease activity parameters including DAS28 and ACR response rate in the four extension period treatment groups. Quality of life improvements at week 72 vs baseline were similarly shown during the extension period in all groups. Newly developed anti-drug antibodies were detected in two patients following study drug infusion in the extension period. Similar pharmacodynamic and safety profiles were observed across groups. CONCLUSION: Long-term use of CT-P10 up to 72 weeks was effective and well tolerated. Furthermore, switching from reference rituximab to CT-P10 in RA was well tolerated and did not result in any clinically meaningful differences in terms of efficacy, pharmacodynamics, immunogenicity and safety. TRAIL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02149121.

Methotrexate withdrawal in patients with rheumatoid arthritis who achieve low disease activity with tofacitinib modified-release 11 mg once daily plus methotrexate (ORAL Shift): a randomised, phase 3b/4, non-inferiority trial.

BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor used for the treatment of rheumatoid arthritis. We assessed the efficacy and safety of tofacitinib after methotrexate withdrawal in patients who achieved low disease activity (LDA) with tofacitinib in combination with methotrexate. METHODS: ORAL Shift was a phase 3b/4 non-inferiority trial in patients aged at least 18 years with moderate-to-severe rheumatoid arthritis and an inadequate response to methotrexate done in 109 centres across 16 countries. After 24 weeks of open-label tofacitinib modified-release 11 mg once daily plus methotrexate, patients who achieved LDA (clinical disease activity index [CDAI] ≤10) were randomly assigned 1:1 via an automated web-based response system to receive tofacitinib plus placebo (tofacitinib monotherapy; ie, masked methotrexate withdrawal) or continue tofacitinib plus methotrexate for 24 weeks in a double-blind manner. The primary endpoint was the least squares mean change from week 24 to week 48 in disease activity score in 28 joints with four variables, including erythrocyte sedimentation rate (DAS28-4[ESR]). The primary analysis was done in all patients who received at least one dose of study treatment in both phases, and safety was assessed in all patients who received at least one dose of study treatment since enrolment. Non-inferiority of tofacitinib monotherapy versus tofacitinib plus methotrexate was declared if the upper bound of the 95% CI for the difference in change in DAS28-4(ESR) between treatment groups was less than 0·6. Safety was assessed in both phases. The trial is registered with ClinicalTrials.gov, NCT02831855, and is complete. FINDINGS: Between Sept 1, 2016, and Nov 1, 2017, 694 patients were enrolled in the open-label phase and 623 received study treatment for 24 weeks. 533 achieved CDAI-defined LDA and were randomly assigned into the double-blind phase (267 in the tofacitinib monotherapy group and 266 in the tofacitinib plus methotrexate group). Three participants in the monotherapy group did not start treatment so were not included in the primary analysis. Non-inferiority was demonstrated (difference 0·30 [95% CI 0·12-0·48]). 107 (41%) of 264 patients in the tofacitinib monotherapy group and 109 (41%) of 266 in the tofacitinib plus methotrexate group had adverse events; five patients from each group discontinued because of adverse events; two patients died in the tofacitinib plus methotrexate group. No new safety findings were reported up to 48 weeks. INTERPRETATION: Patients with rheumatoid arthritis who achieve LDA with a combination of tofacitinib plus methotrexate may consider withdrawing methotrexate without significant worsening of disease activity or unexpected safety issues. FUNDING: Pfizer.

Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthritis: a randomized controlled Phase 3 trial.

This multinational, randomized, double-blind trial, (ClinicalTrials.gov identifier NCT02149121) was designed to demonstrate equivalence in pharmacokinetics and efficacy between CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA). Adults with active RA were treated with CT-P10, United States-sourced RTX (US-RTX; Rituxan®), or European Union-sourced RTX (EU-RTX; MabThera®) at weeks 0 and 2. The co-primary pharmacokinetic endpoints were area under the serum concentration-time curve (AUC) from time zero to last measurable concentration (AUC0-last), AUC from time zero to infinity (AUC0-∞), and maximum concentration (Cmax) after two infusions. The primary efficacy endpoint was change from baseline to week 24 in Disease Activity Score using 28 joints-C-reactive protein (DAS28-CRP). Pharmacodynamics, immunogenicity, and safety were also assessed. 372 patients were randomly assigned to CT-P10 (n = 161) or RTX (n = 211 [US-RTX, n = 151; EU-RTX, n = 60]). For the co-primary pharmacokinetic endpoints, 90% confidence intervals (CI) for ratios of geometric means (CT-P10/US-RTX, CT-P10/EU-RTX or EU-RTX/US-RTX) all fell within the equivalence margin of 80-125%. Adjusted least squares (LS) mean (standard error) change from baseline in DAS28-CRP at week 24 was -2.13 (0.175) for CT-P10 and -2.09 (0.176) for RTX. The 95% CI (-0.29, 0.21) of the estimated treatment difference between CT-P10 and RTX (-0.04) was entirely within the efficacy equivalence margin of ±0.5. Pharmacodynamics, immunogenicity, and safety profiles were similar for CT-P10 and RTX. The pharmacokinetics of CT-P10, US-RTX, and EU-RTX were equivalent. CT-P10 and RTX were also equivalent in terms of efficacy and displayed similar pharmacodynamic, immunogenicity, and safety profiles up to week 24.

Disfunción de la articulación temporomandibular en pacientes con artritis reumatoide / Temporomandibular joint dysfunction in patients with rheumatoid arthritis

La artritis reumatoide (AR) es una enfermedad sistémica crónica inflamatoria caracterizada por una respuesta inmune patogénica que ocasiona daño articular el cual puede ser incapacitante e incluso condicionar una muerte prematura. Entre las articulaciones afectadas puede encontrarse la articulación temporomandibular (ATM) ocasionando dolor, crepitación, inflamación y limitación de los movimientos mandibulares. La disfunción de la ATM es una entidad muy común, por lo que el objetivo de este estudio fue determinar en qué medida los pacientes con AR tienen afección de la ATM comparado con pacientes sanos e identificar las principales diferencias en la presentación clínica, para lo cual se realizó un estudio de casos y controles. Se incluyeron 37 pacientes en cada grupo. En el grupo de pacientes con AR se encontró una afección de la ATM en el 75% de los pacientes (28 casos), mientras que en el grupo control solo el 13,5% (5 casos). Los hallazgos identificados en el grupo de pacientes con AR y disfunción de ATM fueron principalmente desviación mandibular, ruidos articulares, pérdida dental, dolor articular y limitación de la apertura. En este estudio se pudo identificar que existe un riesgo 82% (OR 19,9, IC=0,71-0,89) veces mayor de desarrollar disfunción de ATM en pacientes con AR comparado con pacientes sanos, por lo que resulta de suma importancia realizar revisiones periódicas de la ATM con el fin de identificar signos y síntomas tempranos para así evitar la progresión de la disfunción, lo cual se verá reflejado en una mejor nutrición y calidad de vida del paciente (AU)

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterised by a pathogenic immune response that causes joint damage that can be disabling and even cause premature death. The temporomandibular joint (TMJ) can also be affected, causing pain, crepitus, swelling, and limitation of mandibular movements. TMJ dysfunction is a very common condition, thus the aim of this study was to determine to what extent patients with RA have TMJ dysfunction compared with healthy patients and to identify the main differences in the clinical presentation. A case-control study was performed with the objective of identifying the main differences in the clinical presentation. A total of 37 patients were included in each group. In the group of patients with RA it was found that 75% of patients (28 cases) had TMJ dysfunction, while in the control group there were only 13.5% (5 cases). The findings identified in the group of patients with RA and TMJ dysfunction were mainly: mandibular deviation, joint sounds, tooth loss, joint pain, and limitation of the opening. This study was able to identify that there is an increased risk of 82% (OR 19.9, 95% CI=0.71-0.89) in developing TMJ dysfunction in patients with RA compared with healthy patients. It is concluded that it is important to perform periodic TMJ exploration to be able to identify early signs and symptoms of dysfunction to avoid progression. This would be reflected in better nutrition and quality of life of the patient (AU)

Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques.

OBJECTIVES: To explore the effects of tofacitinib-an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)-with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand. METHODS: In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p<0.05 (vs MTX monotherapy) were considered significant. RESULTS: In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were -1.55 (90% CI -2.52 to -0.58) for tofacitinib + MTX and -1.74 (-2.72 to -0.76) for tofacitinib monotherapy (both p<0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were -0.63 (-1.58 to 0.31) for tofacitinib + MTX and -0.52 (-1.46 to 0.41) for tofacitinib monotherapy (both p>0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy. CONCLUSIONS: These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage. TRIAL REGISTRATION NUMBER: NCT01164579.

Factors associated with mortality and infections in patients with systemic lupus erythematosus with diffuse alveolar hemorrhage.

OBJECTIVE: To evaluate factors associated with mortality and infections in patients with systemic lupus erythematosus (SLE) and diffuse alveolar hemorrhage (DAH). METHODS: A retrospective chart review was carried out for medical admissions of patients with a diagnosis of SLE and DAH in 9 hospitals. Clinical and laboratory data were recorded for each patient at DAH diagnosis. RESULTS: We included 57 episodes of DAH of 50 patients (7 recurrences), 49 women (86%), 14 juvenile SLE (24.6%); 24 had died (42.1%). In the chart review we detected infection in 22 episodes (38.6%): 8 invasive fungal infections, 16 bacterial infections, and 2 patients had both types. In the bivariate analysis, factors associated with mortality were high Acute Physiology and Chronic Health Evaluation II scores, requirement of mechanical ventilation (OR 15.0, 95% CI 1.9 to 662.2), infections (fungal or bacterial; OR 3.2, CI 0.9 to 11.1), renal failure (OR 4.9, CI 1.4 to 18.0), and thrombocytopenia (OR 4.3, CI 1.2 to 15.6). We found similar mortality between children and adults. Infections were associated with treatment for SLE, requirement of mechanical ventilation, hypocomplementemia, and high levels of C-reactive protein. CONCLUSION: Infection is a frequent finding in patients with DAH and SLE; we found similar mortality between adult SLE and juvenile SLE. Factors that we describe associated with infections may influence the therapeutic selection for these patients.

Eficacia de tocilizumab en enfermedad de Still del adulto refractaria; a propósito de 2 casos / Efficacy of tocilizumab in refractory adult-onset Still’s Disease; Report of 2 cases

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Eficacia y tolerabilidad de rituximab en el tratamiento de pacientes con rhupus / Efficacy and tolerability of rituximab in patients with rhupus

El rhupus es una entidad poco común en la que se superponen datos de lupus eritematoso generalizado y artritis reumatoide, predominando con frecuencia las manifestaciones articulares. En muchos casos el tratamiento con fármacos modificadores de la enfermedad no biológicos es insatisfactorio, por lo que se ha intentado el uso de inmunosupresores y fármacos biológicos. Se realizó un estudio prospectivo y abierto para evaluar la eficacia y la tolerabilidad de rituximab en pacientes con rhupus. El objetivo principal fue el cambio en el DAS28 a los 6 meses; fueron objetivos secundarios el cambio en MEX-SLEDAI a los 6 meses, el cambio en DAS28 y MEX-SLEDAI durante el seguimiento, el requerimiento de esteroides y el registro de eventos adversos. Se incluyó a 9 pacientes, todas mujeres, con edad promedio de 43 años y tiempo de evolución de 10 años. Se observó un descenso en la puntuación basal de DAS28 de 5,73 a 3,02 a los 6 meses (p < 0,001). La mejoría en el DAS28 se mantuvo durante el periodo de seguimiento. A los 6 meses, 3 pacientes presentaban remisión por DAS28 y 3 actividad baja. La calificación de MEX-SLEDAI disminuyó de 5 puntos a nivel basal a 1,22 a los 6 meses (p < 0,001) y mantuvo esta mejoría. Se observó una correlación negativa entre la mejoría clínica y los niveles de anti-CCP (r = –0,794; p = 0,011). La dosis de prednisona disminuyó de 11,66 mg/día basal a 0,55 y 1,11 mg/día a los 12 y 24 meses, respectivamente. En general, el tratamiento con rituximab fue bien tolerado durante el estudio. En los pacientes de nuestro estudio, el tratamiento con rituximab mostró ser eficaz tanto en las manifestaciones articulares, con reducción significativa del DAS28, como en otras manifestaciones de lupus, con mejoría del MEX-SLEDAI. Consideramos que esta puede ser una buena opción terapéutica para pacientes con rhupus (AU)

Rhupus in an infrequent disease in which an overlap between lupus eritematosus and rheumatoid arthritis exists. Joint manifestations are prominent and treatment with nonbiological DMARDs is not always satisfactory, so immunosuppressors and biological agents have been tried. A prospective, open clinical study was done to evaluate efficacy and tolerability of rituximab in patients with rhupus. The main objective was a change in DAS28 at 6 months and secondary objectives were a change in MEX-SLEDAI at 6 months, change in DAS28 and MEX-SLEDAI during follow up, steroid requirements and detection of adverse events. We included 9 women with a mean age of 43 years and disease duration of 10 years. A significant reduction in DAS28 was observed (from 5.73 at baseline to 3.02 at 6 months, P<.001). Improvement in DAS28 was maintained during follow up. At 6 months, 3 patients were in remission and 3 had low disease activity. MEX-SLEDAI diminished from 5 points at baseline to 1.22 at 6 months (P<.001). There was a negative correlation between clinical improvement and anti-CCP levels (r=−0.794, P=.011). Mean prednisone dose was reduced from 11.66 mg/day at baseline to 0.55 and 1.11 mg/day at 12 and 24 months. Treatment was well tolerated. In this study rituximab was effective not only for joint affection but also for other manifestations of the disease. We consider that this biological agent can be a good therapeutic option for patients with rhupus (AU)

Efficacy and tolerability of rituximab in patients with rhupus.

Rhupus in an infrequent disease in which an overlap between lupus eritematosus and rheumatoid arthritis exists. Joint manifestations are prominent and treatment with non biological DMARDs is not always satisfactory, so immunosupressors and biological agents have been tried. A prospective, open clinical study was done to evaluate efficacy and tolerability of rituximab in patients with Rhupus. The main objective was a change in DAS28 at 6 months and secondary objectives were a change in MEX-SLEDAI at 6 months, change in DAS28 and MEX-SLEDAI during follow up, steroid requirements and detection of adverse events. We included 9 women with a mean age of 43 years and disease duration of 10 years. A significant reduction in DAS28 was observed (from 5.73 at baseline to 3.02 at 6 months, P<.001). Improvement in DAS28 was maintained during follow up. At 6 months, 3 patients were in remission and 3 had low disease activity. MEX-SLEDAI diminished from 5 points at baseline to 1.22 at 6 months (P<.001). There was a negative correlation between clinical improvement and anti-CCP levels (r=-0,794, P=.011). Mean prednisone dose was reduced from 11.66mg/day at baseline to 0,55 and 1.11mg/day at 12 and 24 months. Treatment was well tolerated. In this study rituximab was effective not only for joint affection but also for other manifestations of the disease. We consider that this biological agent can be a good therapeutic option for patients with rhupus.

Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial.

BACKGROUND: Clinical remission and low disease activity are essential treatment targets in patients with rheumatoid arthritis. Although moderately active rheumatoid arthritis is common, treatment effects in moderate disease have not been well studied. Additionally, optimum use of biologics needs further investigation, including the use of induction, maintenance, and withdrawal treatment strategies. The aim of the PRESERVE trial was to assess whether low disease activity would be sustained with reduced doses or withdrawal of etanercept in patients with moderately active disease. METHODS: In a randomised controlled trial, patients aged between 18 and 70 years with moderately active rheumatoid arthritis (disease activity score in 28 joints [DAS28] >3.2 and ≤5.1) despite treatment with methotrexate were enrolled at 80 centres in Europe, Latin America, Asia, and Australia between March 6, 2008, and Sept 9, 2009. To be eligible, patients had to have been receiving 15-25 mg of methotrexate every week for at least 8 weeks. In an open-label period of 36 weeks, all patients were given 50 mg etanercept plus methotrexate every week. To be eligible for a subsequent double-blind period of 52 weeks, participants had to have achieved sustained low disease activity. These patients were randomly assigned (1:1:1) by an interactive voice-response system to one of three treatment groups: 50 mg etanercept plus methotrexate, 25 mg etanercept plus methotrexate, or placebo plus methotrexate. Patients were stratified in blocks of three by DAS28 response (low disease activity or remission) at week 36. Patients, investigators, data analysts, and study staff were all masked to treatment allocation. The primary endpoint was the proportion of patients with low disease activity at week 88 in the groups given 50 mg etanercept or placebo in the double-blind period. A conditional primary endpoint was the proportion of patients receiving 25 mg etanercept who achieved low disease activity. Modified intention-to-treat populations were used for analyses. This trial is registered with ClinicalTrials.gov, number NCT00565409. FINDINGS: 604 (72.4%) of 834 enrolled patients were eligible for the double-blind period, of whom 202 were assigned to 50 mg etanercept plus methotrexate, 202 to 25 mg etanercept plus methotrexate, and 200 to placebo plus methotrexate. At week 88, 166 (82.6%) of 201 patients who had received at least one dose of 50 mg etanercept and one or more DAS28 evaluations had low disease activity, compared with 84 (42.6%) of 197 who had received placebo (mean difference 40.8%, 95% CI 32.5-49.1%; p<0.0001). Additionally, 159 (79.1%) of 201 patients given 25 mg etanercept had low disease activity at week 88 (mean difference from placebo 35.9%, 27.0-44.8%; p<0.0001). INTERPRETATION: Conventional or reduced doses of etanercept with methotrexate in patients with moderately active rheumatoid arthritis more effectively maintain low disease activity than does methotrexate alone after withdrawal of etanercept. FUNDING: Pfizer.

Terapia biológica, sobrevida y seguridad en padecimientos reumáticos. Resultados del Registro Nacional Biobadamex 1.0 / Patient survival and safety with biologic therapy. Results of the Mexican National Registry Biobadamex 1.0

Mediante registro multicéntrico ambispectivo de 2.047 pacientes con diversas afecciones reumáticas bajo terapia biológica (TxB), incluyendo un grupo control de pacientes con artritis reumatoide (AR) sin TxB, se reporta la supervivencia en la terapia y eventos adversos asociados a su uso. Los diagnósticos más frecuentes son: AR 79,09%; espondilitis anquilosante (EA) 7,96%; artritis psoriásica (APso) 4,40%; lupus eritematoso sistémico (LES) 3,37% y artritis idiopática juvenil (AIJ) 1,17 por ciento. Un análisis de 1.514 casos de la muestra total reportó que la tasa de incidencia para cualquier evento adverso es de 178/1.000 pacientes-año en TxB vs. 109/1.000 pacientes-año en controles con un riesgo relativo (RR) de 1,6 (IC del 95%, 1,4-1,9); para eventos adversos graves un RR de 15,4 (IC del 95%, 3,7-63,0 p < 0,0001). La supervivencia global de TxB es del 80% a 12 meses, el 61% a 24 meses, el 52% a 36 meses y el 45% a 48 meses. La tasa de mortalidad estandarizada (TME) es de 0,23 (IC del 95%, 0,0-49,0) para TxB vs. 0,00 (IC del 95%, 0,0-0,2) para controles. Se concluye que la TxB se asocia a un mayor riesgo de presentar eventos adversos, especialmente infecciosos, en comparación con pacientes sin TxB. La mortalidad de los pacientes expuestos a TxB no es mayor que la esperada para la población general ajustada a edad y sexo (AU)

This work reports patient treatment survival and adverse events related to Biologic Therapy (BT), identified by a multicenter ambispective registry of 2047 rheumatic patients undergoing BT and including a control group of Rheumatoid Arthritis (RA) patients not using BT. The most common diagnoses were: RA 79.09%, Ankylosing Spondilytis 7.96%, Psoriatic Arthritis 4.40%, Systemic Lupus Erythematosus 3.37%, Juvenile Idiopathic Arthritis 1.17%. A secondary analysis included 1514 cases from the total sample and was performed calculating an incidence rate of any adverse events of 178 × 1000/ BT patients per year vs. 1009 x 1000/control group patients per year with a 1.6 RR (IC95% 1.4-1.9). For serious adverse events the RR was: 15.4 (95% CI 3.7-63.0, P<.0001). Global BT survival was 80% at 12 months, 61% at 24 months, 52% at 36 months and 45% at 48 months. SMR: 0.23 (95%CI 0.0-49.0) for BT vs. 0.00 (95%CI 0.0-0.2) for the control group. In conclusion, BT was associated to a higher infection risk and adverse events, compared to other patients. Mortality using BT was not higher than expected for general population with same gender and age (AU)

Patient survival and safety with biologic therapy. Results of the Mexican National Registry Biobadamex 1.0.

This work reports patient treatment survival and adverse events related to Biologic Therapy (BT), identified by a multicenter ambispective registry of 2047 rheumatic patients undergoing BT and including a control group of Rheumatoid Arthritis (RA) patients not using BT. The most common diagnoses were: RA 79.09%, Ankylosing Spondilytis 7.96%, Psoriatic Arthritis 4.40%, Systemic Lupus Erythematosus 3.37%, Juvenile Idiopathic Arthritis 1.17%. A secondary analysis included 1514 cases from the total sample and was performed calculating an incidence rate of any adverse events of 178 × 1000/BT patients per year vs 1009 × 1000/control group patients per year with a 1.6 RR (95% CI 1.4-1.9). For serious adverse events the RR was: 15.4 (95% CI 3.7-63.0, P<.0001). Global BT survival was 80% at 12 months, 61% at 24 months, 52% at 36 months and 45% at 48 months and SMR: 0.23 (95% CI 0.0-49.0) for BT vs 0.00 (95% CI 0.0-0.2) for the control group. In conclusion, BT was associated to a higher infection risk and adverse events, compared to other patients. Mortality using BT was not higher than expected for general population with same gender and age.

Eficacia de rituximab comparado con ciclofosfamida en pacientes con manifestaciones graves de lupus eritematoso generalizado. Estudio aleatorizado y multicéntrico / Efficacy of rituximab versus cyclophosphamide in lupus patients with severe manifestations. A randomized and multicenter study

No existen a la fecha estudios controlados que evalúen la eficacia de rituximab (RTX) comparando con un tratamiento estándar, como ciclofosfamida, en pacientes con lupus eritematoso generalizado (LEG). Objetivo. Comparar la eficacia de RTX con ciclofosfamida en pacientes con manifestaciones graves de LEG. Material y método. Estudio clínico aleatorizado, multicéntrico, controlado y abierto en adultos con LEG activo. Se administró RTX o bolos de ciclofosfamida, con mismo esquema de esteroides. Se evaluó MEX-SLEDAI, dosis de esteroide y eventos adversos, durante 12 meses. Se empleó estadística descriptiva y comparativa. Resultados. Fueron 19 pacientes, 17 mujeres, con edad de: 35,7 años ±12,1, y tiempo de evolución de 5,6 años (0,35–30,8). No hubo diferencias en género, edad, tiempo de evolución, tratamientos previos o actividad de la enfermedad al inicio entre los grupos. Se observó descenso en el MEX-SLEDAI de 12 a 3 en el grupo 1, y de 9 a 2 en el grupo 2 (p=0,80). El grupo que recibió RTX tuvo mejoría más rápida. La dosis acumulada de esteroide fue similar. En ambos grupos se observó reducción en niveles de anti-DNAds e incremento de C3. Los eventos adversos fueron semejantes. Conclusión. Este ensayo clínico comparativo muestra que RTX puede ser tan eficaz como ciclofosfamida, para el control de manifestaciones graves del LEG, con respuesta más rápida. Los eventos adversos inmediatos y mediatos no fueron diferentes. RTX puede considerarse una opción terapéutica adecuada en este tipo de pacientes (AU)

There are no controlled studies that compare the efficacy of RTX with standard treatment, such as cyclophosphamide, in patients with systemic lupus erythematosus (SLE). Objective. The objective of this study was to compare the efficacy of rituximab to that of cyclophosphamide in patients with severe manifestations of SLE. Materials and method. This is a multicenter, randomized open and controlled trial in adults with a diagnosis of active SLE. Patients were randomized into two groups; group 1: treated with RTX and group 2: cyclophosphamide pulses with the same steroid scheme. We registered MEX-SLEDAI, steroid requirements and adverse events for 12 months. Descriptive and comparative statistic analysis was performed. Results. 19 patients were included, 17 females, mean age 35.7±12.1 years and duration of disease 5.6 years (range 0.35 to 30.8 years). There were no differences at baseline regarding gender, age, duration of disease, previous treatments or disease activity between both groups. MEX-SLEDAI was reduced from 12 to 3 in group 1 and from 9 to 2 in group 2 (p=0.80). Nevertheless, patients treated with RTX had a faster improvement. There was no difference in the cumulative steroid dose. Both groups had significant reduction in antinuclear antibody levels and similar increase in C3 levels. Adverse events were similar in both groups. Conclusion. This comparative clinical study in patients with SLE shows that rituximab can be as useful as cyclophosphamide for severe manifestations, maybe showing a faster response. Adverse events were no different. Rituximab should be considered as an adequate alternative for this group of patients (AU)