Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis.

OBJECTIVE: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. METHODS: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. RESULTS: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). CONCLUSIONS: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.

Factors associated with discontinuation of biologics in patients with inflammatory arthritis in remission: data from the BIOBADASER registry.

BACKGROUND: The objectives of this study were to assess the discontinuation of biologic therapy in patients who achieve remission and identify predictors of discontinuation of biologics in patients with inflammatory arthritis in remission. METHODS: An observational retrospective study from the BIOBADASER registry comprising adult patients diagnosed with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) and receiving 1 or 2 biological disease-modifying drugs (bDMARDs) between October 1999 and April 2021. Patients were followed yearly after initiation of therapy or until discontinuation of treatment. Reasons for discontinuation were collected. Patients who discontinued bDMARDs because of remission as defined by the attending clinician were studied. Predictors of discontinuation were explored using multivariable regression models. RESULTS: The study population comprised 3,366 patients taking 1 or 2 bDMARDs. Biologics were discontinued owing to remission by 80 patients (2.4%): 30 with RA (1.7%), 18 with AS (2.4%), and 32 with PsA (3.9%). The factors associated with a higher probability of discontinuation on remission were shorter disease duration (OR: 0.95; 95% CI: 0.91-0.99), no concomitant use of classic DMARDs (OR: 0.56; 95% CI: 0.34-0.92), and shorter usage of the previous bDMARD (before the decision to discontinue biological therapy) (OR: 1.01; 95% CI: 1.01-1.02); in contrast, smoking status (OR: 2.48; 95% CI: 1.21-5.08) was associated with a lower probability. In patients with RA, positive ACPA was associated with a lower probability of discontinuation (OR: 0.11; 95% CI: 0.02-0.53). CONCLUSIONS: Discontinuation of bDMARDs in patients who achieve remission is uncommon in routine clinical care. Smoking and positive ACPA in RA patients were associated with a lower probability of treatment discontinuation because of clinical remission.

Effects of COVID-19 vaccination on disease activity in patients with rheumatoid arthritis and psoriatic arthritis on targeted therapy in the COVIDSER study.

OBJECTIVE: To investigate the influence of COVID-19 vaccination on disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients under targeted therapies. PATIENTS AND METHODS: 1765 vaccinated patients COVID-19, 1178 (66.7%) with RA and 587 (33.3%) with PsA from the COVID-19 registry in patients with rheumatic diseases (COVIDSER) project, were included. Demographics, disease characteristics, Disease Activity Score in 28 joints (DAS28) and targeted treatments were collected. DAS28-based flare rates and categorised disease activity distribution prevaccination and post vaccination were analysed by log-linear regression and contingency analyses, respectively. The influence of vaccination on DAS28 variation as a continuous measure was evaluated using a random coefficient model. RESULTS: The distribution of categorised disease activity and flare rates was not significantly modified by vaccination. Log-linear regression showed no significant changes in the rate of flares in the 6-month period after vaccination compared with the same period prior to vaccination in neither patients with RA nor patients with PsA. When DAS28 variations were analysed using random coefficient models, no significant variations in disease activity were detected after vaccination for both groups of patients. However, patients with RA treated with Janus kinase inhibitors (JAK-i) (1) and interleukin-6 inhibitor (IL-6-i) experienced a worsening of disease activity (1.436±0.531, p=0.007, and 1.201±0.550, p=0.029, respectively) in comparison with those treated with tumour necrosis factor inhibitor (TNF-i). Similarly, patients with PsA treated with interleukin-12/23 inhibitor (IL-12/23-i) showed a worsening of disease activity (4.476±1.906, p=0.019) compared with those treated with TNF-i. CONCLUSION: COVID-19 vaccination was not associated with increased rate of flares in patients with RA and PsA. However, a potential increase in disease activity in patients with RA treated with JAK-i and IL-6-i and in patients with PsA treated with IL-12/23-i warrants further investigation.

Bone mineral density status and frequency of osteoporosis and clinical fractures in 155 patients with psoriatic arthritis followed in a university hospital / Estado de la densidad mineral ósea y frecuencia de osteoporosis y de fracturas clínicas en 155 pacientes con artritis psoriásica evaluados en un hospital universitario

Objective: To assess the bone mineral density (BMD) and the frequency of osteoporosis and clinical fractures in a large group of Spanish patients with psoriatic arthritis (PsA). Patients and methods: BMD was determined by DXA in all the patients who were willing to participate and had peripheral PsA regularly evaluated in a tertiary university hospital. All patients underwent a physical examination and general laboratory analysis. We gathered demographic and clinical variables related with BMD and risk of fractures. We also recorded the history of clinical low impact fractures. The population of reference to calculate T-score and Z-score came from a Spanish database. Results: One hundred and fifty-five patients were included (64 postmenopausal women, 26 premenopausal women and 65 men). The clinical forms of PsA were: 46% oligoarticular and 54% polyarticular. Mean disease duration was 13.7±9.4 years and mean ESR was 21.8±13.9mm/h; 66% of patients had received glucocorticoid treatment. We found no differences in BMD status between the patients and the Spanish general population, neither in the whole series nor in each defined subgroup. Frequency of osteoporosis was 16%; it was higher in postmenopausal women (28%) than in men (9%) or premenopausal women (4%). Frequency of clinical fractures was 13%; it accounted specially in postmenopausal women

Objetivo: Analizar el estado de la densidad mineral ósea (DMO) así como la frecuencia de osteoporosis y de fracturas clínicas en una serie de pacientes con artritis psoriásica (APs). Pacientes y Método: Se determinó la DMO, mediante DXA, en todos los pacientes con APs periférica, evaluados de forma periódica en un hospital universitario, que aceptaron participar en el estudio. Se les practicó una exploración física y un estudio analítico y se recabó información acerca de variables clínicas relacionadas con la DMO y con el riesgo de fractura. Asimismo, se analizó si existía el antecedente de haber presentado una fractura de bajo impacto. El cálculo del T-score y del Z-score se realizó a partir de una base de datos de población española. Resultados: Se incluyeron 155 pacientes (64 mujeres posmenopáusicas, 26 mujeres premenopáusicas y 65 varones). En el 46% de los casos la APS adoptó un patrón oligoarticular y en el 54% poliarticular. La duración media de la enfermedad fue 13.7 ± 9.4 años, el valor medio de la VSG fue de 21.8 ± 13.9 mm/h; el 66% de los pacientes habían recibido tratamiento con glucocorticoides. No se observaron diferencias entre la DMO de los pacientes y la de la población general, ni en la globalidad de la serie, ni en ninguno de los tres grupos. La frecuencia global de osteoporosis se situó en el 16%; fue más alta en las mujeres posmenopáusicas (28%) que en los varones (9%) y que en las mujeres premenopáusicas (4%). La frecuencia de fracturas clínicas fue del 13%; acontecieron fundamentalmente en las mujeres posmenopáusicas (AU)

Bone mineral density status and frequency of osteoporosis and clinical fractures in 155 patients with psoriatic arthritis followed in a university hospital.

OBJECTIVE: To assess the bone mineral density (BMD) and the frequency of osteoporosis and clinical fractures in a large group of Spanish patients with psoriatic arthritis (PsA). PATIENTS AND METHODS: BMD was determined by DXA in all the patients who were willing to participate and had peripheral PsA regularly evaluated in a tertiary university hospital. All patients underwent a physical examination and general laboratory analysis. We gathered demographic and clinical variables related with BMD and risk of fractures. We also recorded the history of clinical low impact fractures. The population of reference to calculate T-score and Z-score came from a Spanish database. RESULTS: One hundred and fifty-five patients were included (64 postmenopausal women, 26 premenopausal women and 65 men). The clinical forms of PsA were: 46% oligoarticular and 54% polyarticular. Mean disease duration was 13.7±9.4 years and mean ESR was 21.8±13.9mm/h; 66% of patients had received glucocorticoid treatment. We found no differences in BMD status between the patients and the Spanish general population, neither in the whole series nor in each defined subgroup. Frequency of osteoporosis was 16%; it was higher in postmenopausal women (28%) than in men (9%) or premenopausal women (4%). Frequency of clinical fractures was 13%; it accounted specially in postmenopausal women. CONCLUSIONS: The magnitude of the problem of osteoporosis in PsA seems to be mild.

Age at treatment predicts reason for discontinuation of TNF antagonists: data from the BIOBADASER 2.0 registry.

OBJECTIVES: To assess the retention rate of TNF antagonists in elderly patients suffering from chronic arthropathies and to identify predictive variables of discontinuation by inefficacy or by adverse events (AEs). METHODS: All patients treated with TNF antagonists in BIOBADASER 2.0, with a diagnosis of either RA or spondyloarthritis (SpA: AS and PsA) were included and classified as <65 (younger) or ≥65 years of age (older) at start of the treatment. Cumulative incidence function for discontinuation (inefficacy or AE) was estimated as being the alternative reason for a competing risk. Competing-risks regression models were used to measure the association between study groups, covariates and reason for discontinuation. RESULTS: A total of 4851 patients were studied; 2957 RA (2291 in the younger group and 666 in the older group) and 1894 SpA (1795 in the younger group and 99 in the older group). Retention curves were statistically differently stratified by age groups, with the SpA younger group having the largest retention rate. Competing-risks regression models showed that in the older group, AEs were the most common reason for discontinuation regardless of the diagnosis of the patient and TNF antagonist molecule, whereas in the younger group, the most common cause of discontinuation was inefficacy. CONCLUSION: In conclusion, factors predicting discontinuation of TNF antagonists due to AEs are older age and diagnosis of RA. On the other hand, younger age predicts discontinuation due to lack of efficacy.

[Systematic review: safety and efficacy of anti-TNF in elderly patients]. / Revisión sistemática: eficacia y seguridad del tratamiento anti-TNF en pacientes ancianos.

OBJECTIVE: To evaluate whether the safety and efficacy of anti-TNF treatments in elderly patients with rheumatic diseases is similar than the safety and efficacy of the same drugs in younger patients. METHODS: Systematic review. We performed a systematic search in MEDLINE (Pubmed), EMBASE (Ovid), and the Cochrane Library Plus. Abstracts published in the American and European rheumatology congresses and articles in Reumatología Clínica were also reviewed. RESULTS: Ten studies fulfilled the inclusion criteria. Studies show a similar efficacy in elderly and younger patients. The differences between the young and the elderly regarding DAS28 reductions before and after are very small: 0.04 in the Geneway et al study and 0.0 in the Mariette et al study, as well as in the before and after HAQ: 0.04 (Geneway et al), 0.18 (Schiff et al) and 0.06 (Mariette et al).Adverse events reported in elderly and younger patients are 83.3% and 77.1% respectively with etanercept, as reported by Fleischmann; 27.2% vs 12.5%, p=0.19, as reported by Chevillotte, and the rate of withdrawal due to an adverse event was 57,8% vs 29,2% with infliximab, p=0.03, 36% vs 15% p=0.06 with adalimumab and 10,3% and 9,5%, with no significant p value, as reported by Massara. CONCLUSIONS: The information to assess the efficacy and safety of anti-TNF therapy in elderly patients was obtained in all cases from sub analyses and therefore bias is possible. We can say, with a low to moderate level of evidence, that elderly patients undergoing anti-TNF treatments have a higher number of adverse events, and similar efficacy, when compared with younger patients.

Revisión sistemática: eficacia y seguridad del tratamiento anti-TNF en pacientes ancianos / Systematic review: Safety and efficacy of anti-TNF in elderly patients

Objetivo. Evaluar si la seguridad y la eficacia de los tratamientos anti TNF en pacientes ancianos con enfermedades reumáticas inflamatorias es similar a la seguridad y eficacia en pacientes jóvenes. Métodos. Revisión sistemática. Se realizó una búsqueda bibliográfica en Medline (vía Pubmed), Embase (vía Ovid) y Cochrane Library Plus, abstracts publicados en los congresos americano y europeo de reumatología y artículos publicados en Reumatología Clínica. Resultados. Diez estudios cumplían los criterios de inclusión. Los estudios coinciden en una eficacia similar en jóvenes y ancianos. Las diferencias en la reducción del DAS28 de antes y después entre jóvenes y ancianos son muy pequeñas: 0,04 en el estudio de Geneway et al y 0,0 en el de Mariette et al; así como en el HAQ de antes y después: 0,04 (Geneway et al), 0,18 (Schiff et al) y 0,06 (Mariette et al). Los efectos adversos descritos en ancianos y jóvenes respectivamente son de 83,3% y 77,1% con etanercept, según Fleischmann; 27,2% vs 12,5%, p=0,19, según Chevillotte; y 57,8% vs 29,2% con infliximab, p=0,03, 36% vs 15% p=0,01 con adalimumab y de 10,3% vs 9,5% con etanercept, p no significativa, según Massara. Conclusiones. La información para evaluar la eficacia y seguridad de los anti TNF en ancianos procede de subanálisis y por tanto se encuentra sujeta a sesgos. Podemos decir, con un nivel de evidencia bajo o moderado, que los ancianos presentan más acontecimientos adversos y similar eficacia que en los no ancianos cuando se tratan con agentes anti TNF(AU)

Objective. To evaluate whether the safety and efficacy of anti-TNF treatments in elderly patients with rheumatic diseases is similar than the safety and efficacy of the same drugs in younger patients. Methods. Systematic review. We performed a systematic search in MEDLINE (Pubmed), EMBASE (Ovid), and the Cochrane Library Plus. Abstracts published in the American and European rheumatology congresses and articles in Reumatología Clínica were also reviewed. Results. Ten studies fulfilled the inclusion criteria. Studies show a similar efficacy in elderly and younger patients. The differences between the young and the elderly regarding DAS28 reductions before and after are very small: 0.04 in the Geneway et al study and 0.0 in the Mariette et al study, as well as in the before and after HAQ: 0.04 (Geneway et al), 0.18 (Schiff et al) and 0.06 (Mariette et al).Adverse events reported in elderly and younger patients are 83.3% and 77.1% respectively with etanercept, as reported by Fleischmann; 27.2% vs 12.5%, p=0.19, as reported by Chevillotte, and the rate of withdrawal due to an adverse event was 57,8% vs 29,2% with infliximab, p=0.03, 36% vs 15% p=0.06 with adalimumab and 10,3% and 9,5%, with no significant p value, as reported by Massara. Conclusions. The information to assess the efficacy and safety of anti-TNF therapy in elderly patients was obtained in all cases from sub analyses and therefore bias is possible. We can say, with a low to moderate level of evidence, that elderly patients undergoing anti-TNF treatments have a higher number of adverse events, and similar efficacy, when compared with younger patients(AU)