Martina Steiner's research while affiliated with Hospital Universitario Infanta Sofía and other places

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Publications (27)


Impact of systemic therapies on SARS-CoV-2 antibody seroprevalence in patients with immune-mediated diseases
  • Article

May 2024

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4 Reads

Medicina Clínica (English Edition)

Liz Romero-Bogado

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Martina Steiner

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[...]

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Timeline of immunosuppressive treatments and/or biologics administered in patients with noninfectious uveitis who required at least two treatments, according to diagnosis. Shaded: treatment that resolved the uveitis; RAAU: recurrent acute anterior uveitis; AS: axial spondyloarthropathy; MTX: methotrexate; ADA: adalimumab; MFM: mycophenolate mofetil; INF: infliximab; TOZ: tocilizumab; SAR: sarilumab; CYA: cyclosporine; SSZ: sulfasalazine.
Change in visual acuity of the affected eye(s) in patients with noninfectious uveitis and visual acuity <1 before treatment according to the first immunosuppressant administered (median; Q1 and Q3). Patients who started with vision of 1 were excluded. Decimal scores were converted to logMAR using the formula logMAR = −log (decimal acuity).
Timeline of immunosuppressive and/or biologic treatments administered in patients with noninfectious uveitis and macular edema, according to diagnosis. Shading: treatment that resolved macular edema. * Patient who developed macular edema while on MFM treatment. RAAU: recurrent acute anterior uveitis; CYA: cyclosporine; MTX: methotrexate; ADA: adalimumab; TOZ: tocilizumab; MFM: mycophenolate mofetil; INF: infliximab; SAR: sarilumab.
Sociodemographic, clinical, and treatment * characteristics of all patients with UNI (n = 361) and comparison of untreated patients and those treated with IS/BT.
Cont.
An Observational Study in the Real Clinical Practice of the Treatment of Noninfectious Uveitis
  • Article
  • Full-text available

February 2024

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32 Reads

Journal of Clinical Medicine

Journal of Clinical Medicine

Background: The aim of this study was to describe the characteristics of patients with uveitis associated with an immunologic or idiopathic disease that requires immunosuppressive treatment and the response to such treatments in real clinical practice. Methods: An observational, descriptive, longitudinal, and retrospective study of a cohort of patients diagnosed with noninfectious uveitis was performed. To assess the response to treatment, we evaluated the change in visual acuity, vitritis, and the presence of macular edema. Results: We included 356 patients. Overall, 12% required treatment with systemic corticosteroids, and 66 patients (18.5%) required immunosuppressive/biological treatment, with methotrexate being the most used (55%). Immunosuppressive drugs were used in 59 cases (in 56 patients, as the first choice of treatment and for 3 patients as the second choice after treatment with biologics). Treatment with biologics was the first choice in 10 patients out of 66 (15%), and 34 (48%) required them at some time during the disease, with adalimumab being the most commonly used. Thirty-five patients (53%) needed to switch drugs due to a lack of response to the first one. There were no differences between different drugs in the resolution of vitritis and improvement in vision. Conclusions: The use of systemic corticosteroids and immunosuppressive/biologics was necessary for a high number of patients with noninfectious uveitis. In our series, tocilizumab was significantly more effective in the resolution of macular edema.

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Impacto de las terapias sistémicas en la seroprevalencia de anticuerpos contra el SARS-CoV-2 en pacientes con enfermedades inmunomediadas

February 2024

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7 Reads

Medicina Clínica

Objective: To determine the seroprevalence of SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMID) treated with biologic (bDMARDs) or synthetic targeted disease-modifying antirheumatic drugs (tsDMARDs). Methods: An observational, descriptive, prospective and cross-sectional study of analytical prevalence analysis was conducted in patients with IMID with bDMARDs or tsDMARDs. Seroprevalence was compared by measuring immunoglobulinG (IgG) against SARS-CoV-2 between October/2020 and May/2021. Results: A total of 550 IMID's patients were studied, all of them on treatment with bDMARDs or tsDMARDs. The seroprevalence of the total patient group was 16% (88/550). Patients receiving therapy with tumor necrosis factor alpha inhibitors (TNFi) had a higher seroprevalence compared to other biologic and synthetic targeted therapies (OR: 1.792 [95%CI: 1.088-2.951]; P=.021). The influence on seroprevalence of concomitant use with b/tsDMARDs of conventional synthetic DMARDs (csDMARDs) was also analyzed. A lower seroprevalence was demonstrated in the group of patients treated with TNFi and methotrexate together, compared with those on TNFi monotherapy, 10.1 vs 24.1% (OR: 0.355 [95%CI: 0.165-0.764]; P=.006). No significant differences were found with the other DMARDs. Regarding IMIDs, no differences in seroprevalence were identified between the different disease groups. Conclusion: Patients on treatment with TNFα inhibitors have better humoral response compared to the other b/tsDMARDs. However, when associated with methotrexate the seroprevalence decreases significantly.


Figure 1. Timeline of immunosuppressive treatments and/or biologics administered in patients with non-infectious uveitis who required at least two treatments, according to diagnosis.
Sociodemographic, clinical and treatment* characteristics of all patients with UNI (n= 361) and comparison of patients treated and untreated with IS/BT.
Observational Study in Real Clinical Practice of the Treatment of Non-Infectious Uveitis

January 2024

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22 Reads

To describe the characteristics of patients with uveitis associated with an immunologic or idio-pathic disease that requires immunosuppressive treatment and the response to such treatments in real clinical practice. Observational, descriptive, longitudinal, and retrospective study of a cohort of patients diagnosed with idiopathic uveitis or autoimmune disease-related uveitis. To assess the response to treatment we have evaluated the change in visual acuity and vitritis and the presence of macular edema. We included 356 patients. Twelve percent required treatment with systemic corticosteroids and 66 patients (18.5%) immunosuppressive/biological treatment, with metho-trexate being the most used (55%). Immunosuppressive drugs were used in 59 cases the least re-sponsive being mycophenolate mofetil. Ten patients of the 66 (15%) started treatment with bio-logics. Thirty-five patients (53%) needed to switch drugs due to a lack of response to the first one. There were no differences between different drugs in the resolution of vitritis and improvement of vision. The disappearance of macular edema was achieved in all patients treated with tocilizumab. The use of systemic corticosteroids and Immunosuppressive/biologics was necessary for a high number of patients with non-infectious uveitis. In our series tocilizumab was significantly more effective in the resolution of macular edema.


Seroprevalencia del SARS-CoV-2 en los pacientes con enfermedades inmunomediadas en tratamiento con terapias biológicas y sintéticos dirigidos

December 2023

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20 Reads

Revista chilena de infectología

Introducción: La seroprevalencia del SARS-CoV-2 en las enfermedades inflamatorias inmunomediadas (IMID) sigue siendo fuente de controversia. Objetivo: Comparar la seroprevalencia de anticuerpos (Ac) anti SARS-CoV-2 en pacientes con IMID en tratamientos con fármacos antirreumáticos modificadores de la enfermedad biológicos (FAMEb) o sintéticos dirigidos (FAMEsd) frente a un grupo de personas sin IMID. Métodos: Estudio de pacientes con IMID y tratamientos con FAMEb y FAMEsd y de individuos sin IMID. Mediante la técnica de inmunoensayo por quimioluminiscencia indirecta, se determinaron las serologías IgG frente al SARS-CoV-2 entre octubre/2020 y mayo/2021. Resultados: Se estudiaron 1.100 sujetos, 550 pacientes con IMID y 550 personas sin IMID. Se observó una seroprevalencia de 16% (88/550) en los pacientes frente a 19,3% (106/550) en el grupo de personas sin IMID, sin significación estadística (OR 0,790 [IC 95% 0,558-1,118]). Comparando los tratamientos con FAMEb o FAMEsd, se observó una tendencia a una menor seroprevalencia con rituximab, en relación con los individuos sin IMID (OR 0,296 [IC 95% 0,0871,007]). Asimismo, se encontró menor seroprevalencia en los pacientes que además de su FAMEb recibían tratamiento con metotrexato, en comparación con el grupo de personas sin IMID (OR 0,432 [IC 95% 0,223-0,835]). Conclusiones: Las IMID en tratamiento con FAMEb o FAMEsd no influyen en la seroprevalencia frente al SARS-CoV-2 de los pacientes. El tratamiento concomitante con metotrexato disminuye de forma significativa la seroprevalencia en estos pacientes.


Evaluation of humoral vaccine response to RZV in IMIDs patients under JAKi treatment. The figure shows the increase in anti gE VZV antibody concentrations, measured with CLIA, comparing the initial antibody concentration (black dots) and the post-vaccination (orange dots) serology in serum.
The Real-World Study of Immunogenicity and Safety of the Adjuvant Recombinant Vaccine against Varicella Zoster Virus in Patients with Immune-Mediated Inflammatory Diseases Treated with Janus Kinase Inhibitors

October 2023

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25 Reads

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1 Citation

Background. The risk of herpes zoster reactivation is increased in immunocompromised patients, especially in those with immune-mediated inflammatory diseases (IMIDs) on Janus kinase inhibitor (JAKi) treatment. The recombinant subunit herpes zoster vaccine (RZV) is a non-live vaccine, recently approved for this subgroup of patients, which shows high rates of vaccine effectiveness, with few adverse effects reported in clinical trials. Purpose. The aim of this real-world study was to determine the immunogenicity and safety of RZV in IMID patients on JAKi treatment. Methods. The increase in the concentration of anti-gE antibody for varicella zoster virus post-vaccination, compared to the pre-vaccination concentration, was analyzed to test the humoral immune response. Adverse effects after the first and second vaccine doses were registered. Results. In total, 49 patients were analyzed, and a fourfold increase in antibody concentration was achieved in almost 40% of subjects, with only one serious local adverse effect. Discussion. The resulting immunogenicity was lower than that observed in clinical trials, probably due to the presence of immune disease and immunosuppressive treatment, and to the fact that this was a real-world study. No differences in response according to age, previous virus zoster reactivation, or concomitant treatments were found. Conclusions. RZV was well tolerated and reached the immune response objective in 40% of patients. These results reinforce the importance of including RZV vaccination for immunosuppressed patients. Real-world studies regarding vaccine effectiveness are still needed in order to gain a full understanding of the response to RZV in this group of patients.



Frequency of COVID-19 in Different Types of IMIDs and Treatments (bDMARDs or tsDMARDs) in the 902 Patients Included in the Study
Frequency of Symptoms and Treatments in 70 Patients With COVID-19 and IMIDs Treated With bDMARDs or tsDMARDs
Incidence of COVID-19 in 902 Patients With Immunomediated Inflammatory Diseases Treated With Biologics and Targeted Synthetic Disease-Modifying Antirheumatic Drugs-Findings From the BIOCOVID Study

March 2021

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90 Reads

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3 Citations

Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases

Objectives: The aim of this study was to examine the incidence of coronavirus disease 2019 (COVID-19) among patients with immunomediated inflammatory diseases (IMIDs) treated with biologic or targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) and to evaluate the influence of either IMIDs or related therapies on the incidence and evolution of COVID-19. Methods: This observational, cross-sectional study was conducted from January 31, 2020, to May 15, 2020. Data of 902 patients were obtained from clinical records in hospitals, primary care units, and community pharmacies. Inclusion criteria were adults with IMIDs treated with bDMARDs or tsDMARDs who started therapy 3 months prior to study commencement. Patients with poor adherence to treatments were excluded. COVID-19 was classified as "definitive" (severe acute respiratory syndrome coronavirus 2 polymerase chain reaction [PCR]-positive), "possible" (characteristic symptoms and negative PCR), and "suspected" (characteristic symptoms but PCR not performed). Results: COVID-19 was diagnosed in 70 patients (11 definitive, 19 possible, and 40 suspected). The cumulative incidence of definitive COVID-19 was 1.2%. When considering all cases, the incidence was 7.8%. Patients on biosimilars tumor necrosis factor blockers were more likely to have a diagnosis of COVID-19 (odds ratio, 2.308; p < 0.001). Patients on anti-B-cell therapies had a lower incidence of infections (p = 0.046). Low rates of hospitalization (14.3%), pneumonia (14.3%), death (2.9%), or thrombosis (2.9%) were observed, and 94.3% of patients recovered. Conclusions: The cumulative incidence of confirmed cases of COVID-19 was similar to the general population, with generally low hospitalization, intensive care management, and mortality rates. COVID-19 incidence was less frequent in patients with more severe immunosuppression.


Figure 3. Patients with OT > 50% against each serotype, depending on the biological agent received. Abatacept and anakinra were not included due to the scarce number of patients. St (serotype), OT (opsonization titers).
Number and percentage of patients that presented final OT 1 against each one of the six serotypes studied.
Impact of Biological Therapies on the Immune Response after Pneumococcal Vaccination in Patients with Autoimmune Inflammatory Diseases

February 2021

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76 Reads

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14 Citations

Vaccines

Vaccines

Patients with different autoimmune inflammatory diseases (AIID) on biological therapy are at risk of pneumococcal disease. Adults with inflammatory arthropathies, connective tissue diseases, psoriasis, or inflammatory bowel disease on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included in this study. Patients completed a protocol combining the pneumococcal vaccines PCV13 and PPV23. Immune response against pneumococcal serotypes 1, 3, 7F, 14, 19A, and 19F were assessed evaluating functional antibodies by an opsonophagocytosis killing assay (OPKA). In this study, 182 patients with AIID completed the sequential vaccination protocol. Patients on etanercept tended to achieve OPKA titers against a larger number of serotypes than the rest of patients on other biological therapies, while adalimumab was associated to a lower number of serotypes with OPKA titers. Rituximab was not associated with a worse response when compared with the rest of biological agents. Not glucocorticoids, nor synthetic disease-modifying antirheumatic drugs, interfered with the immune response. OPKA titers against serotype 3 which is one of the most prevalent, was obtained in 44% of patients, increasing up to 58% in those on etanercept. Hence, almost 50% of patients on biological therapy achieved functional antibodies after the administration of a complete pneumococcal vaccination protocol.


Serological response to influenza vaccine in patients with autoimmune inflammatory diseases: Results of RIER study

January 2021

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11 Reads

Medicina Clínica (English Edition)

Background Influenza vaccine is recommended for patients with autoimmune inflammatory diseases (AIID) on biological therapy. Objective To evaluate whether serological response to Influenza vaccine obtained in patients on biological therapy is similar to that achieved in patients on synthetic disease-modifying anti-rheumatic drugs (DMARDs) and that obtained in healthy controls. Methods We designed a cohort study in which patients with AIID, 68 on biological therapy and 46 on synthetic DMARDs, as well as 48 healthy controls, were included and vaccinated during the 2015–2016 influenza season. ELISA was used to measure Influenza antigen (Ag) A and B antibodies, before and after vaccination. Results After vaccination, 88.24% of patients on biologics, 71.74% of those on synthetic DMARDs and 89.58% of healthy controls, presented detectable antibodies against antigen A, while 42.65% of subjects on biologics, 41.30% of those on DMARDs and 54.17% of healthy subjects were seropositive against Ag B. We did not find statistical differences. Conclusions In our study, biological therapy is not associated with worse serological response.


Citations (15)


... В Российской Федерации зарегистрирована рекомбинантная белковая вакцина против HZ, которая имеет благоприятный профиль безопасности у пациентов ИВРЗ, что позволяет преодолеть риск, связанный с живыми аттенуированными вакцинами. По данным литературы, частота обострения ИВРЗ после иммунизации указанной вакциной варьирует от 6,1 до 16%, при этом указания на взаимосвязь ухудшения течения с вакцинацией, выполненной на фоне активной фазы болезни, отсутствуют [32][33][34][35]. По данным одного из крупных академических медицинских центров США, частота обострения РА после иммунизации указанной вакциной была меньше таковой у невакцинированных больных в течение 6-месячного периода наблюдения (6,7 и 30%, соответственно. ...

Reference:

Vaccinoprophylaxis of infections and activity of immuno-inflammatory rheumatic diseases: pro et contra
The Real-World Study of Immunogenicity and Safety of the Adjuvant Recombinant Vaccine against Varicella Zoster Virus in Patients with Immune-Mediated Inflammatory Diseases Treated with Janus Kinase Inhibitors
Vaccines

Vaccines

... The efficacy and safety of vaccines have not been studied in patients receiving tocilizumab for NMOSD or any other neuroimmunological disease. In a study of patients with various other autoimmune inflammatory diseases, antibody responses to pneumococcal polysaccharide vaccination were suppressed in people receiving tocilizumab in comparison with those in people receiving rituximab 63 . However, a different study showed that responses to hepatitis B vaccination were stronger in people receiving tocilizumab than in people receiving rituximab in autoimmune diseases 64 . ...

Impact of Biological Therapies on the Immune Response after Pneumococcal Vaccination in Patients with Autoimmune Inflammatory Diseases
Vaccines

Vaccines

... This choroidal response to the steroid treatment may further support that eyes with non-ocular sarcoidosis are under subclinical choroidal inflammation. Unfortunately, we could not identify serum biomarkers reflecting localized and subclinical choroidal inflammation status in eyes with nonocular sarcoidosis; Choroidal thickness in the non-ocular sarcoidosis group did not show significant association with CRP (an inflammation marker in various inflammatory systemic diseases) [27][28][29] or ACE (a biomarker for systemic sarcoidosis, correlated with the granuloma Table 3 Factors associated with choroidal thickness SLCC Sattler layer-choriocapillaris complex, HL Haller layer, ACE angiotensin converting enzyme, CRP C-reactive protein, BCVA best corrected visual acuity, SE spherical equivalent, IOP intraocular pressure ** Statistically significant (p < 0.05) and *borderline significant (p < 0.1); Linear regression analysis for continuous variable and Chi-squared test for categorical variables burden and disease severity) levels [30,31]. Caution is needed in interpreting these results due to a time gap between blood tests and OCT acquisition caused by referral-to-ophthalmologic screening duration (mean 33.38 ± 41.12 days). ...

Choroidal Thickness Is a Biomarker Associated With Response to Treatment in Ankylosing Spondylitis
  • Citing Article
  • July 2020

Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases

... [4][5][6] There is some evidence that HBV vaccination is effective in patients under conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (68%-95% seroprotection 7 8 vs >85% in healthy adults 9 ), but it is currently unclear whether this also applies to bDMARDs, with little and conflicting evidence available. [10][11][12][13] We therefore aimed to assess the efficacy and safety of HBV vaccination in patients with IA treated with bDMARDs. ...

Evaluation of the immune response to hepatitis B vaccine in patients on biological therapy: results of the RIER cohort study
  • Citing Article
  • April 2020

Clinical Rheumatology

... Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease that primarily invades the spine and involves the cuboid iliac joint (1). The disability rate of patients with AS is high and AS has a serious impact on quality of life (2,3). Studies have shown that AS is associated with genetics, infection, immunity, inflammatory cell infiltration, cytokine imbalance and other factors (4,5). ...

Measuring Choroid Thickness as a Marker of Systemic Inflammation in Patients With Ankylosing Spondylitis
  • Citing Article
  • February 2020

Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases

... However, insufficient data from vulnerable populations (such as clinically unstable patients with inflammatory diseases undergoing long-term biologic treatments) may still raise some concerns about the quality of the evidence available. An accurate schedule with adequate time intervals between mAb treatment and influenza vaccine may be the key to a better response, changing immunogenicity from 25% up to 80% in the case of rituximab [49]. ...

Antibody responses to influenza vaccine in patients on biological therapy: Results of RIER cohort study
  • Citing Article
  • November 2019

Medicina Clínica (English Edition)

... To date, consensus definitions of tenosynovitis and enthesitis in children are still lacking; therefore, current definitions validated in adults are still applied to children [30,31]. Efforts to delineate pediatric definitions of tenosynovitis and enthesitis are in progress ( Figures 5 and 6) [32,33]. ...

FRI0635 ULTRASOUND IN THE ASSESSMENT OF TENOSYNOVITIS IN JUVENILE IDIOPATHIC ARTHRITIS: SYSTEMATIC LITERATURE REVIEW

Annals of the Rheumatic Diseases

... Response to the trivalent influenza vaccine in patients currently receiving or recently completing treatment with rituximab has been examined in several studies. Patients with RA who had received rituximab showed an impaired humoral response compared with RA patients receiving non-biologic disease modifying anti-rheumatic drugs (DMARDs) or healthy controls [59][60][61][62][63]. However, the cellular immune response to influenza vaccination was not affected by rituximab, with similar levels of influenza-specific CD4+ cells in patients treated with rituximab or DMARDs [59]. ...

Antibody responses to influenza vaccine in patients on biological therapy: Results of RIER cohort study
  • Citing Article
  • May 2019

Medicina Clínica

... [12] Factors pertinent to NAFLD including obesity, [13,14] cardiovascular risk factors [15] and insulin resistance [16] have also proven to be negatively correlated with CT. Even there is robust evidence suggesting lower CT in in ammatory vascular disease such as systemic lupus erythematosus [17] , behçet [18] , scleroderma [19] and so forth [20] . Purportedly, choroidal changes in NAFLD patients remain obscure. ...

Choroidal and retinal thickness in systemic autoimmune and inflammatory diseases: A review
  • Citing Article
  • April 2019

Survey of Ophthalmology