Clinical predictors of multiple failure to biological therapy in patients with rheumatoid arthritis.

BACKGROUND: Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians. OBJECTIVES: This study aims to determine the percentage of rheumatoid arthritis (RA) patients who fail to respond to subsequent bDMARDs, describe their characteristics, and identify specific baseline and early features during the first bDMARD as possible predictors of consecutive multiple bDMARD failure. METHODS: This is a longitudinal study involving RA patients from the prospective biological cohort drawn from the La Paz University Hospital RA Registry (RA-Paz), starting a bDMARD during the years 2000 to 2019. Patients who presented insufficient response (due to primary or secondary inefficacy) to at least three bDMARDs or two bDMARDs with different mechanism of action were considered multi-refractory (MR-patients). Patients who achieved low disease activity or remission (by DAS-28) with the first bDMARD and maintained this over a follow-up period of at least 5 years were considered non-refractory (NR-patients). RESULTS: A total of 41 out of 402 (10%) patients were MR-patients and 71 (18%) NR-patients. In the multivariate analysis, the presence of erosions, younger age, higher baseline DAS-28 and mostly achieving delta-DAS < 1.2 after 6 months of the first bDMARD (OR 11.12; 95% CI 3.34-26.82) were independently associated with being MR-patients to bDMARDs. CONCLUSIONS: In our cohort, 10% of patients with RA were observed to have multi-refractoriness to bDMARDs. This study supports the contention that younger patients with erosive disease and especially the early absence of clinical response to the first bDMARDs are predictors of multi-refractoriness to consecutive biologics. Hence, patients with these characteristics should be monitored more closely and may benefit from personalized treatments.

Are we treating women patients with real axial spondyloarthritis?

INTRODUCTION: During the last years, regulatory agencies raised some relevant concerns with regard to the possibility of administrating biological therapy (BT) to non-SpA patients. Especially, the possibility of treating women with fibromyalgia as non-radiographic axSpA (nr-axSpA) was mentioned. OBJECTIVES: To evaluate if the gender distribution and clinical pattern of patients with axSpA initiating biological therapy (BT) was modified in clinical practice after its approval for non radiographic-axSpA (nr-axSpA). METHODS: Baseline dataset from a prospective ongoing cohort including all patients with axSpA treated with BT at the Rheumatology Department of University Hospital La Paz, Madrid, Spain, was analysed. Patient's characteristics and disease activity parameters were collected. Based on the approval indication date of BT for nr-axSpA, patients were classified in two periods according to the starting date for the first BT: period 1 (before 2013) and period 2 (during or after 2013). Gender distribution and disease' characteristics were compared between both groups using Chi-square and Student-t tests. RESULTS: In total, 385 patients initiated BT: 266 (69%) in period 1 and 119 (31%) in period 2. No significant differences between both periods were observed regarding gender distribution (38% and 39% of women; p = 0.8). Out of those patients with nr-axSpA initiating BT in period 2, the majority (60%) were men. Women starting BT in period 2 had significantly higher systemic inflammation and mobility restriction compared with women in period 1 [median (interquartile range) CRP 10.2 mg/l (3.0-24.9) vs 3.2 mg/l (2.0-9.4); p = 0.02 and BASMI 2.7 (1.8-3.5) vs. 2.0 (1.2-2.6); p = 0.01, respectively]. In addition, they also presented significantly higher disease activity [BASDAI 6.5 (5.4-8.0) vs. 5.8 (4.6-6.8); p = 0.02; ASDAS, mean (SD) 3.6 ± 3.4 vs. 3.2 ± 1.0; p = 0.02, respectively] and more functional limitation [BASFI 5.7 (3.8-6.7) vs. 4.3 (2.0-6.1); p = 0.01, respectively] than men treated in period 2. CONCLUSIONS: In our clinical practice, the frequency of women who started BT did not increase since their approval for nr-axSpA. Women treated with BT after 2012 had more objective disease activity parameters than before their approval for nr-axSpA treatment.

Anti-TNF-α therapy in refractory uveitis associated with sarcoidosis: Multicenter study of 17 patients.

OBJECTIVES: To assess anti-TNF-α therapy response in uveitis associated with sarcoidosis refractory to conventional immunosuppressive therapy. METHODS: Open-label, multicenter, retrospective study on patients with sarcoid uveitis who underwent anti-TNF-α therapy because of inadequate response to conventional therapy including corticosteroids and at least 1 systemic synthetic immunosuppressive drug. The main outcome measurements were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness, and immunosuppression load. RESULTS: A total of 17 patients (8 men; 29 affected eyes; mean ± standard deviation age 38.4 ± 16.8; range: 13-76 years) were studied. The patients had bilateral hilar lymphadenopathy (58.8%), lung parenchyma involvement (47.1%), peripheral lymph nodes (41.2%), and involvement of other organs (52.9%). Angiotensin-converting enzyme was elevated in 58.8%. The most frequent ocular pattern was bilateral chronic relapsing panuveitis. The first biologic agent used was adalimumab in 10 (58.8%) and infliximab in 7 (41.2%) cases. Infliximab 5mg/kg intravenously every 4-8 weeks and adalimumab 40mg subcutaneously every 2 weeks were the most common administration patterns. In most cases anti-TNF-α therapy was given in combination with immunosuppressive drugs. The mean duration of follow-up was 33.9 ± 17.1 months. Significant improvement was observed following anti-TNF-α therapy. Baseline results versus results at 2 years from the onset of biologic therapy were the following: the median of cells in the ocular anterior chamber (interquartile range-IQR) 0.5 (0-2) versus 0 (0-0) (p = 0.003), vitritis 0 (0-1.25) versus 0 (0-0) (p = 0.008), macular thickness (391.1 ± 58.8 versus 247 ± 40.5µm) (p = 0.028), and visual acuity 0.60 ± 0.33 versus 0.74 ± 0.27; p = 0.009. The median daily (interquartile range) dose of prednisone was also reduced from 10 (0-30)mg at the onset of the anti-TNF-α therapy to 0 (0-0)mg at 2 years (p = 0.02). Significant reduction was also achieved in the immunosuppressive load. CONCLUSION: Anti-TNF-α therapy is effective in sarcoid uveitis patients refractory to conventional immunosuppressive therapy. Infliximab and adalimumab allowed a substantial reduction in prednisone dose despite having failed standard therapy.

Anti-TNF-α therapy in patients with refractory uveitis due to Behçet's disease: a 1-year follow-up study of 124 patients.

OBJECTIVE: The aim of this study was to assess the efficacy of anti-TNF-α therapy in refractory uveitis due to Behçet's disease (BD). METHODS: We performed a multicentre study of 124 patients with BD uveitis refractory to conventional treatment including high-dose corticosteroids and at least one standard immunosuppressive agent. Patients were treated for at least 12 months with infliximab (IFX) (3-5 mg/kg at 0, 2 and 6 weeks and then every 4-8 weeks) or adalimumab (ADA) (usually 40 mg every 2 weeks). The main outcome measures were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness and immunosuppression load. RESULTS: Sixty-eight men and 56 women (221 affected eyes) were studied. The mean age was 38.6 years (s.d. 10.4). HLA-B51 was positive in 66.1% of patients and uveitis was bilateral in 78.2%. IFX was the first biologic agent in 77 cases (62%) and ADA was first in 47 (38%). In most cases anti-TNF-α drugs were used in combination with conventional immunosuppressive drugs. At the onset of anti-TNF-α therapy, anterior chamber and vitreous inflammation was observed in 57% and 64.4% of patients, respectively. In both conditions the damage decreased significantly after 1 year. At baseline, 50 patients (80 eyes) had macular thickening [optical coherence tomography (OCT) >250 µm] and 35 (49 eyes) had cystoid macular oedema (OCT>300 µm) that improved from 420 µm (s.d. 119.5) at baseline to 271 µm (s.d. 45.6) at month 12 (P < 0.01). The best-corrected visual acuity and the suppression load also showed significant improvement. After 1 year of follow-up, 67.7% of patients were inactive. Biologic therapy was well tolerated in most cases. CONCLUSION: Anti-TNF-α therapy is effective and relatively safe in refractory BD uveitis.

Utilidad en Medicina del Trabajo de protocolos clínicos para establecer un diagnóstico precoz de trastornos musculoesqueléticos / Usefulness in occupational medicine of clinical protocols to establish an early diagnosis of musculoskeletal disorders

Los trastornos musculoesqueléticos con frecuencia son atendidos en las consultas de los médicos del trabajo, siendo importante su diagnóstico diferencial con las enfermedades reumáticas. Las enfermedades reumáticas son, en su mayoría, enfermedades crónicas que producen gran morbilidad, discapacidad e incapacidad, con un alto coste social e individual. Es importante distinguir la patología mecánica/traumática de la patología de origen inflamatorio, y es prioritaria la derivación de los pacientes al reumatólogo cuando la sospecha diagnóstica es de conectivopatía, artritis inflamatoria o espondiloartritis. Para realizar una adecuada derivación es necesario conocer el diagnóstico diferencial de los síndromes musculoesqueléticos, así como desarrollar protocolos de derivación y unidades de reciente comienzo. El propósito de esta publicación es la difusión de protocolos clínicos que permiten establecer un diagnóstico precoz de trastornos musculoesqueléticos y facilitar al especialista en medicina del trabajo la distinción entre procesos mecánicos e inflamatorios (AU)

Musculoskeletal disorders are frecuently attended by occupational psysicians, being important the diferential diagnosis with rheumatic disorders. Rheumatic disorders are mostly chronic diseases that can cause high morbidity and disability, with a social and individual high cost. It is important to distinguish the mechanical or traumatic pathology from inflammatory conditions; and a priority referral to a rheumatologist is needed when the suspected diagnosis is connective tissue disease, spondyloarthropathy, or inflammatory arthritis. To make an appropriate referral it is necessary to know the differential diagnosis of musculoskeletal syndromes, to develop referral protocols and to create new onset diagnosis units (recent onset arthritis and spondylitis units). The purpose of this report is to show clinical protocols designed to establish an early diagnosis in musculoskeletal disorders and facilitate the occupational medicine specialists the distinction between mechanical and inflammatory diseases (AU)

Validez y utilidad de la ecografía en el síndrome del túnel carpiano / Validity and usefulness of echography in the carpal tunnel syndrome

Objetivo: Evaluar la validez y la utilidad de la ecografía en el síndrome del túnel carpiano (STC). Material y método: Estudio ecográfico ciego y prospectivo en 75 carpos de 42 pacientes consecutivos con sospecha de STC. Se utiliza la electromiografía (EMG) como prueba de referencia. Se miden distintos parámetros ecográficos y mediante curvas ROC se estiman las probabilidades tras la prueba para los diferentes cortes del área de sección transversal del mediano (AST). Se analiza la fiabilidad entre explorador y lector con tres exploradores diferentes y dos lectores. Finalmente se efectúa un estudio de costes y de satisfacción del paciente. Resultados: Las medias de los parámetros ecográficos son significativamente mayores en el grupo con STC. Hay una alta concordancia entre la ecografía y la conducción nerviosa. Un punto de corte del AST en 9,5 mm2 clasifica correctamente el 83% de los casos (sensibilidad del 88% y especificidad del 67%). Un punto de corte mayor de 14 mm2 o menor de 7 mm2 tiene una probabilidad tras la prueba para el STC del 100% de especificidad y sensibilidad respectivamente. Los coeficientes de correlación intraclase (ICC) entre observadores fueron 0,915-0,980, y entre lectores, 0,912-0,987. La ecografía puede resultar más económica y ahorrar en el estudio 3.217,59 euros (42,9 euros por muñeca sintomática). El malestar percibido por los pacientes fue significativamente menor: EVA, 6,3 con ecografía frente a 56 con el EMG (p < 0,0005). Conclusiones: La ecografía es fiable y válida para definir si hay o no STC. La ecografía como prueba de primera línea es coste-efectiva y más satisfactoria para los pacientes (AU)

Objective: To evaluate the accuracy and utility of ultrasonography for the diagnosis of carpal tunnel syndrome (CTS). Material and method: Prospective and blind study of 75 wrists in 42 consecutive patients with suspected CTS. Electrodiagnostic testing (EDT) was used as gold standard. We measure different ultrasonographic parameters and based on a fitted receiver operating characteristic curve, we estimated post-test probabilities for the proximal, middle and distal cross-sectional area of median nerve. We analyzed interobserver and interreader reliability by 3 different explorers and 2 different readers, cost and the patient discomfort. Results: Mean ultrasound measurements were significantly higher in the EDT positive group. There was a high concordance between sonography and nerve conduction. A cut-off of 9.5 mm2 resulted in the correct classification of 83% of cases (sensitivity 88% and specificity 67%). Conversely, a cut-off of >14 mm2 or <7 mm2 had excellent power to rule in CTS, with a post-test probability of 100% of specificity and sensitivity respectively. The interobserver acquisition ICC was 0.915-0.980, and the inter-reader ICC was 0.912-0.987. Ultrasound cost savings in this study were J3217.59 (J42.9 per symptomatic wrist) and the discomfort perceived by the patient was significantly lesser 6.3 vs 56 in EDT (P<.0005). Conclusions: Ultrasound median nerve crosssectional area is reliable and may be used to accurately rule in or rule out CTS. Sonography as a first-line test is cost-effective and is more satisfactory to the patients (AU)

[Validity and usefulness of echography in the carpal tunnel syndrome]. / Validez y utilidad de la ecografía en el síndrome del túnel carpiano.

OBJECTIVE: To evaluate the accuracy and utility of ultrasonography for the diagnosis of carpal tunnel syndrome (CTS). MATERIAL AND METHOD: Prospective and blind study of 75 wrists in 42 consecutive patients with suspected CTS. Electrodiagnostic testing (EDT) was used as gold standard. We measure different ultrasonographic parameters and based on a fitted receiver operating characteristic curve, we estimated post-test probabilities for the proximal, middle and distal cross-sectional area of median nerve. We analyzed interobserver and interreader reliability by 3 different explorers and 2 different readers, cost and the patient discomfort. RESULTS: Mean ultrasound measurements were significantly higher in the EDT positive group. There was a high concordance between sonography and nerve conduction. A cut-off of 9.5 mm(2) resulted in the correct classification of 83% of cases (sensitivity 88% and specificity 67%). Conversely, a cut-off of >14 mm(2) or <7 mm(2) had excellent power to rule in CTS, with a post-test probability of 100% of specificity and sensitivity respectively. The interobserver acquisition ICC was 0.915-0.980, and the inter-reader ICC was 0.912-0.987. Ultrasound cost savings in this study were €J3217.59 (€42.9 per symptomatic wrist) and the discomfort perceived by the patient was significantly lesser 6.3 vs 56 in EDT (P <.0005). CONCLUSIONS: Ultrasound median nerve crosssectional area is reliable and may be used to accurately rule in or rule out CTS. Sonography as a first-line test is cost-effective and is more satisfactory to the patients.