RESUMEN
OBJECTIVES: The study aimed to evaluate the effect of adding a non-steroidal anti-inflammatory drug (NSAID), celecoxib (CEL), to a tumour necrosis factor inhibitor (TNFi), golimumab (GOL), compared with TNFi monotherapy on radiographic spinal progression in patients with radiographic axial spondyloarthritis (r-axSpA) over 2 years. METHODS: R-axSpA patients, having risk factors for radiographic progression (high disease activity plus C reactive protein >5 mg/L and/or ≥1 syndesmophyte(s)), underwent a 12-week run-in phase with GOL 50 mg every 4 weeks. In the core phase (96 weeks), only patients with a good clinical response at week 12 were randomised (1:1) to GOL+CEL 200 mg two times per day (combination therapy) or GOL monotherapy. The primary endpoint was radiographic progression assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change at week 108 in the intent-to-treat population. RESULTS: A total of 128 patients were enrolled in the run-in phase; and 109 patients were randomised at week 12 to monotherapy (n=55) or combination therapy (n=54). At week 108, 97 (52 vs 45) patients completed the study. The change in mSASSS at week 108 was 1.7 (95% CI 0.8 to 2.6) in the monotherapy vs 1.1 (95% CI 0.4 to 1.8) in the combination therapy groups (p=0.79). New syndesmophytes occurred in 25% of patients in the monotherapy vs 11% of patients in the combination therapy groups (p=0.12). During the study, no significant differences in adverse events and serious adverse events were observed between the groups. CONCLUSIONS: Combination therapy with GOL+CEL did not demonstrate statistically significant superiority over GOL monotherapy in retarding radiographic spinal progression over 2 years in r-axSpA.
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Espondiloartropatías , Espondilitis Anquilosante , Humanos , Antiinflamatorios no Esteroideos/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Radiografía , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/patología , Espondilitis Anquilosante/tratamiento farmacológico , Celecoxib/uso terapéutico , Espondiloartropatías/tratamiento farmacológico , Progresión de la EnfermedadRESUMEN
BACKGROUND: Inhibition of interleukin (IL)-1 represents a promising treatment option in adult-onset Still's disease (AOSD). OBJECTIVE: To investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multicentre, double-blind, randomised, placebo-controlled trial. METHODS: Patients with AOSD and active joint involvement (tender and swollen joint counts of ≥4 each) were treated with canakinumab (4 mg/kg, maximum 300 mg subcutaneous every 4 weeks) or placebo. The primary endpoint was the proportion of patients with a clinically relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28>1.2). RESULTS: At enrolment, patients had high active disease with a mean DAS28(ESR) of 5.4 in the canakinumab and 5.3 in the placebo group, respectively. In the intention-to-treat analysis, 12 patients (67%) in the canakinumab group and 7 patients (41%) in the placebo group fulfilled the primary outcome criterion (p=0.18). In the per-protocol analysis, significantly higher American College of Rheumatology (ACR) 30% (61% vs 20%, p=0.033), ACR 50% (50% vs 6.7%, p=0.009) and ACR 70% (28% vs 0%, p=0.049) response rates were observed in the canakinumab group compared with the placebo group. Two patients in the canakinumab group experienced a serious adverse event. CONCLUSION: Although the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Enfermedad de Still del Adulto/tratamiento farmacológico , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVES: The effectiveness of TNF inhibitors in RA has been shown to be affected by obesity. No such effect has been found for abatacept and rituximab, while for tocilizumab results are ambiguous. Additionally, it remains unresolved whether sex is an effect modifier for obesity. We investigated the impact of obesity on the drug effectiveness of conventional synthetic or biologic DMARDs, taking into account potential sex-specific differences. METHODS: Data from 10 593 RA patients included in the German observational cohort study Rheumatoid Arthritis: oBservation of BIologic Therapy (RABBIT) since 2009 were analysed. Patients had to have a BMI ≥18.5 kg/m2, at least one follow-up and 6 months of observation time. The influence of obesity on drug effectiveness was investigated by regression analysis, adjusting for potential confounders. RESULTS: Obesity had a negative impact on improvement in the DAS with 28 joints using ESR as an inflammation marker of -0.15 (95% CI: -0.26; -0.04) units for women receiving conventional synthetic DMARDs, -0.22 (95% CI: -0.31; -0.12) units for women receiving TNF inhibitors, -0.22 (95% CI: -0.42; -0.03) units for women receiving tocilizumab and -0.41 (95% CI: -0.74; -0.07) units for men receiving tocilizumab. Overall, no negative obesity effects on the effectiveness of rituximab and abatacept were found. CONCLUSION: Obesity has a negative impact on the effectiveness of cytokine-targeted but not cell-targeted therapies in daily practice, affecting more outcomes and therapies in women than in men. Overall, no effects of obesity on treatment effectiveness were found for rituximab and abatacept.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Obesidad/complicaciones , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Abatacept/administración & dosificación , Abatacept/uso terapéutico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/administración & dosificación , Artritis Reumatoide/complicaciones , Productos Biológicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/administración & dosificaciónRESUMEN
Objectives: The aim of the study was to investigate the functional relevance of the development of structural damage in the spine in patients with early axial spondyloarthritis (axSpA). Methods: Altogether, 210 patients with early axSpA (symptom duration ⩽10 years) who completed a 2-year clinical and radiographic follow-up in the GErman SPondyloarthritis Inception Cohort were included. An association between structural damage in the spine [modified Stoke AS Spine Score (mSASSS)] and functional status (the BASFI) or spinal mobility (the BASMI) was assessed in a longitudinal linear mixed model analysis; both unstandardized (ß) and standardized (ßstand) regression coefficients were calculated. Results: There was an association between mSASSS and BASFI: ß = 0.05 (95% CI: 0.03, 0.08) and ßstand = 0.20 (95% CI: 0.11, 0.59) adjusted for disease activity parameters (the BASDAI and CRP), the presence of definite radiographic sacroiliitis and sex. An association between mSASSS and BASMI was stronger: ß = 0.08 (95% CI: 0.05, 0.11) and ßstand = 0.41 (95% CI: 0.25, 0.57) adjusted for the same parameters. These data indicate that, over time, an increase of 20 or 12 mSASSS points would be responsible for an increase of one BASFI or one BASMI point, respectively. Disease activity (BASDAI) also showed a significant association with BASFI [ß = 0.79 (95% CI: 0.71, 0.86) and ßstand = 0.71 (95% CI: 0.63, 0.77)] and BASMI [ß = 0.22 (95% CI: 0.15, 0.30) and ßstand = 0.28 (95% CI: 0.18, 0.37)]. Conclusion: Structural damage in the spine and disease activity are both determinants of the functional status and spinal mobility in early axSpA.
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Radiografía/métodos , Rango del Movimiento Articular/fisiología , Columna Vertebral/diagnóstico por imagen , Espondiloartritis/diagnóstico , Adulto , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Masculino , Morbilidad/tendencias , Curva ROC , Índice de Severidad de la Enfermedad , Espondiloartritis/epidemiología , Espondiloartritis/fisiopatología , Factores de TiempoRESUMEN
In Germany, Tocilizumab (TCZ) is used for the treatment of rheumatoid arthritis both in biologic-naïve patients and those with previous failures of biologic disease-modifying antirheumatic drugs (bDMARDs). The long-term effectiveness and retention rates of TCZ in patients with different numbers of prior bDMARD failures has rarely been investigated. We included 885 RA patients in the analyses, enrolled with the start of TCZ between 2009 and 2015 in the German biologics register RABBIT. Patients were stratified according to prior bDMARD failures: no prior bDMARD or 1, 2 or ≥ 3 bDMARD failures. We applied Kaplan-Meier methods and Cox-regression to examine treatment adherence as well as linear mixed effects models to investigate effectiveness over 3 years of follow-up. Compared to biologic-naïve patients, those with prior bDMARD failures at start of TCZ were younger but had significantly longer disease duration and more comorbidities. DAS28 at baseline and loss of physical function were highest in patients with ≥ 3 bDMARD failures. During follow-up, patients with up to two bDMARD failures on average reached low disease activity (LDA, DAS28 < 3.2). Those with ≥ 3 prior bDMARDs had a slightly lower response. However, after 3 years, nearly 50% of them achieved LDA. Treatment continuation on TCZ therapy was similar in patients with ≤ 2 bDMARD failures but significantly lower in those with ≥ 3 bDMARD failures. TCZ seems to be similarly effective in patients with no, one or two prior bDMARD failures. The majority of patients achieved LDA already after 6 months and maintained it over a period of 3 years. TCZ proved effective even in the high-risk group of patients with more than two prior bDMARD failures.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/administración & dosificación , Sustitución de Medicamentos , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Productos Biológicos/efectos adversos , Comorbilidad , Esquema de Medicación , Femenino , Alemania , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Sistema de Registros , Factores de Riesgo , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
OBJECTIVES: Some studies have reported a possible association between exposure to tumour necrosis factor (TNF) inhibitors and an increased risk of melanoma. The aim of this study was to investigate the incidence of invasive cutaneous melanomas in patients with rheumatoid arthritis (RA) treated with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy. METHODS: Eleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country-specific general population of each register as reference, age, sex and calendar year standardised incidence ratios (SIRs) of invasive histology-confirmed cutaneous melanoma were calculated within each register. Pooled SIR and incidence rate ratios (IRRs) comparing biologic cohorts to biologic-naïve were calculated across countries by taking the size of the register into account. RESULTS: Overall 130â 315 RA patients with a mean age of 58â years contributing 579â 983 person-years were available for the analysis and 287 developed a first melanoma. Pooled SIRs for biologic-naïve, TNFi and rituximab-exposed patients were 1.1 (95% CI 0.9 to 1.4), 1.2 (0.99 to 1.6) and 1.3 (0.6 to 2.6), respectively. Incidence rates in tocilizumab and abatacept-exposed patients were also not significantly increased. IRR versus biologic-naïve patients were: TNFi 1.1 (95% CI 0.8 to 1.6); rituximab 1.2 (0.5 to 2.9). CONCLUSIONS: This large European collaborative project did not confirm an overall increased risk of melanoma following exposure to TNFi.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Melanoma/epidemiología , Sistema de Registros , Neoplasias Cutáneas/epidemiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Abatacept/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , Productos Biológicos/uso terapéutico , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Rituximab/uso terapéuticoRESUMEN
BACKGROUND: Lymphomas comprise a heterogeneous group of malignant diseases with highly variable prognosis. Rheumatoid arthritis (RA) is associated with a twofold increased risk of both Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). It is unknown whether treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) affect the risk of specific lymphoma subtypes. METHODS: Patients never exposed to (bionaïve) or ever treated with bDMARDs from 12 European biologic registers were followed prospectively for the occurrence of first ever histologically confirmed lymphoma. Patients were considered exposed to a bDMARD after having received the first dose. Lymphomas were attributed to the most recently received bDMARD. RESULTS: Among 124 997 patients (mean age 59 years; 73.7% female), 533 lymphomas were reported. Of these, 9.5% were HL, 83.8% B-cell NHL and 6.8% T-cell NHL. No cases of hepatosplenic T-cell lymphoma were observed. Diffuse large B-cell lymphoma (DLBCL) was the most frequent B-cell NHL subtype (55.8% of all B-cell NHLs). The subtype distributions were similar between bionaïve patients and those treated with tumour necrosis factor inhibitors (TNFi). For other bDMARDs, the numbers of cases were too small to draw any conclusions. Patients with RA developed more DLBCLs and less chronic lymphocytic leukaemia compared with the general population. CONCLUSION: This large collaborative analysis of European registries has successfully collated subtype information on 533 lymphomas. While the subtype distribution differs between RA and the general population, there was no evidence of any modification of the distribution of lymphoma subtypes in patients with RA treated with TNFi compared with bionaïve patients.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Linfoma/epidemiología , Linfoma/etiología , Europa (Continente)/epidemiología , Femenino , Humanos , Linfoma/patología , Linfoma de Células B/epidemiología , Linfoma de Células B/etiología , Linfoma no Hodgkin/epidemiología , Linfoma no Hodgkin/etiología , Linfoma de Células T/epidemiología , Linfoma de Células T/etiología , Masculino , Persona de Mediana Edad , Sistema de Registros , Factores de Riesgo , Inhibidores del Factor de Necrosis TumoralRESUMEN
Effective drug selection is the current challenge in rheumatoid arthritis (RA). Treatment failure may follow different pathomechanisms and therefore require investigation of molecularly defined subgroups. In this exploratory study, whole blood transcriptomes of 68 treatment-naïve early RA patients were analyzed before initiating MTX. Subgroups were defined by serologic and genetic markers. Response related signatures were interpreted using reference transcriptomes of various cell types, cytokine stimulated conditions and bone marrow precursors. HLA-DRB4-negative patients exhibited most distinctive transcriptional differences. Preponderance of transcripts associated with phagocytes and bone marrow activation indicated response and transcripts of T- and B-lymphocytes non-response. HLA-DRB4-positive patients were more heterogeneous, but also linked failure to increased adaptive immune response. RT-qPCR confirmed reliable candidate selection and independent samples of responders and non-responders the functional patterning. In summary, genomic stratification identified different molecular pathomechanisms in early RA and preponderance of innate but not adaptive immune activation suggested response to MTX therapy.
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Inmunidad Adaptativa/genética , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Cadenas HLA-DRB4/genética , Inmunidad Innata/genética , Metotrexato/uso terapéutico , Adulto , Anciano , Alelos , Artritis Reumatoide/inmunología , Femenino , Genómica , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: To date, only a single controlled trial provided evidence that non-steroidal anti-inflammatory drugs (NSAIDs) given continuously reduce radiographic progression compared with an on-demand therapy over 2â years in patients with ankylosing spondylitis (AS). In the current study, we tested whether such an effect of NSAIDs could be confirmed in another randomised trial. METHODS: Patients with AS were randomised for treatment with either continuous (150â mg/day) or on-demand diclofenac for 2â years. Tumour necrosis factor-blocker treatment was not allowed during the entire study period. The primary outcome was the difference in radiographic progression in the spine as measured by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) scored by two readers blinded to treatment arm and time point. RESULTS: 62 of 85 patients enrolled in the continuous arm and 60 of 82 enrolled in the on-demand arm completed the study. The mSASSS progression was numerically higher in the continuous group (1.28 (0.7 to 1.9) vs 0.79 (0.2 to 1.4)) (p=0.39). If only patients were analysed who were either C reactive protein positive or had syndesmophytes at baseline, there was again a higher radiographic progression in the continuous versus the on-demand group: 1.68 (0.7 to 2.6) vs 0.96 (0.0 to 1.9) and 2.11 (1.1 to 3.1) vs 0.95 (0.0 to 1.9), respectively. There was no difference between the two treatment groups regarding adverse events. CONCLUSIONS: In our study, continuous treatment with diclofenac over 2â years did not reduce radiographic progression compared with on-demand treatment in AS. TRIAL REGISTRATION NUMBERS: EudraCt-no 2007-007637-39; ClinicalTrials.gov NCT00715091.
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Antiinflamatorios no Esteroideos/administración & dosificación , Diclofenaco/administración & dosificación , Espondilitis Anquilosante/tratamiento farmacológico , Adulto , Antiinflamatorios no Esteroideos/efectos adversos , Diclofenaco/efectos adversos , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Índice de Severidad de la Enfermedad , Método Simple Ciego , Espondilitis Anquilosante/diagnóstico por imagen , Resultado del TratamientoRESUMEN
There is convincing evidence for the known and unambiguously accepted beneficial effects of glucocorticoids at low dosages. However, the implementation of existing recommendations and guidelines on the management of glucocorticoid therapy in rheumatic diseases is lagging behind. As a first step to improve implementation, we aimed at defining conditions under which long-term glucocorticoid therapy may have an acceptably low level of harm. A multidisciplinary European League Against Rheumatism task force group of experts including patients with rheumatic diseases was assembled. After a systematic literature search, breakout groups critically reviewed the evidence on the four most worrisome adverse effects of glucocorticoid therapy (osteoporosis, hyperglycaemia/diabetes mellitus, cardiovascular diseases and infections) and presented their results to the other group members following a structured questionnaire for final discussion and consensus finding. Robust evidence on the risk of harm of long-term glucocorticoid therapy was often lacking since relevant study results were often either missing, contradictory or carried a high risk of bias. The group agreed that the risk of harm is low for the majority of patients at long-term dosages of ≤5â mg prednisone equivalent per day, whereas at dosages of >10â mg/day the risk of harm is elevated. At dosages between >5 and ≤10â mg/day, patient-specific characteristics (protective and risk factors) determine the risk of harm. The level of harm of glucocorticoids depends on both dose and patient-specific parameters. General and glucocorticoid-associated risk factors and protective factors such as a healthy lifestyle should be taken into account when evaluating the actual and future risk.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Cuidados a Largo Plazo/métodos , Enfermedades Reumáticas/tratamiento farmacológico , Comités Consultivos , Consenso , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Humanos , Factores de Riesgo , Factores de TiempoRESUMEN
OBJECTIVES: This meta-analysis investigates the efficacy of tumour necrosis factor α (TNFα) blockers versus placebo for the treatment of ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). METHODS: A systematic literature search was conducted independently by two reviewers. Double-blind randomised controlled trials (RCTs) investigating the efficacy of adalimumab, certolizumab, etanercept, golimumab or infliximab in approved dosages in comparison with placebo were included. The use of concomitant non-steroidal antirheumatic drugs was allowed. The outcome parameters were improvement in disease activity and function measured by the Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI) and ASAS40 response. The effect sizes of the changes in BASDAI/BASFI between TNFα blocker and placebo comparator groups were calculated. Mixed effect models were applied separately for RCTs with AS and nr-axSpA patients and differences between those groups were evaluated in a joint model. RESULTS: 20 studies with data from 3096 patients were included in the analysis: 15 studies with AS patients, four with nr-axSpA patients and one with both. For AS patients, TNFα blockers showed better efficacy than placebo for BASDAI (effect size 1.00), BASFI (effect size 0.67) and ASAS40 response (OR 4.7). For nr-axSpA patients, the differences were smaller (effect sizes 0.73, 0.57; OR 3.6). However, after adjustment for the year of publication as a proxy for disease severity, no differences in the effect sizes between the AS and nr-axSpA trials were observed. CONCLUSIONS: Compared with placebo, TNFα blockers improve disease activity and functional capacity clinically meaningful for both AS and nr-axSpA patients.
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Antirreumáticos/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Certolizumab Pegol , Método Doble Ciego , Etanercept , Humanos , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Inmunoglobulina G/uso terapéutico , Infliximab , Polietilenglicoles/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Espondiloartritis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
OBJECTIVES: To investigate the impact of disease activity, the course of the disease, its treatment over time, comorbidities and traditional risk factors on survival. METHODS: Data of the German biologics register RABBIT were used. Cox regression was applied to investigate the impact of time-varying covariates (disease activity as measured by the DAS28, functional capacity, treatment with glucocorticoids, biologic or synthetic disease modifying antirheumatic drugs (DMARDs)) on mortality after adjustment for age, sex, comorbid conditions and smoking. RESULTS: During 31â 378 patient-years of follow-up, 463 of 8908 patients died (standardised mortality ratio: 1.49 (95% CI 1.36 to 1.63)). Patients with persistent, highly active disease (mean DAS28 > 5.1) had a significantly higher mortality risk (adjusted HR (HRadj)=2.43; (95% CI 1.64 to 3.61)) than patients with persistently low disease activity (mean DAS28 < 3.2). Poor function and treatment with glucocorticoids >â 5â mg/d was significantly associated with an increased mortality, independent of disease activity. Significantly lower mortality was observed in patients treated with tumour necrosis factor α (TNFα) inhibitors (HRadj=0.64 (95% CI 0.50 to 0.81), rituximab (HRadj=0.57 (95% CI 0.39 to 0.84), or other biologics (HRadj=0.64 (95% CI 0.42 to 0.99), compared to those receiving methotrexate. To account for treatment termination in patients at risk, an HRadj for patients ever exposed to TNFα inhibitors or rituximab was calculated. This resulted in an HRadj of 0.77 (95% CI 0.60 to 0.97). CONCLUSIONS: Patients with long-standing high disease activity are at substantially increased risk of mortality. Effective control of disease activity decreases mortality. TNFα inhibitors and rituximab seem to be superior to conventional DMARDs in reducing this risk.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/mortalidad , Anciano , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Rituximab , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
OBJECTIVE: The aim of this study was to assess the degree of fluctuation of osteitis on MRI during long-term treatment with etanercept (ETN) in patients with early axial SpA (axSpA) with active inflammation (osteitis) on whole-body MRI in the spine and/or the SI joints at baseline. METHODS: We analysed MRI data from 328 SI joint quadrants and 943 spine vertebral units (VUs) in terms of osteitis in the pooled data set of 41 patients who were treated with ETN for 3 consecutive years. Scoring was performed by two blinded radiologists at baseline, year 2 and year 3. RESULTS: Through years 2 and 3, osteitis on MRI resolved completely in 56 of 144 (38.9%) SI joint quadrants and in 20 of 40 (50%) VUs affected at baseline, while persistent osteitis was found in 24 of 144 (16.7%) SI joint quadrants and in 8 of 40 (20.0%) spine VUs. The development of new osteitis in sites that were free of osteitis at baseline only occurred in 2 of 131 (1.5%) SI joint quadrants and in 3 of 862 (0.4%) spine VUs in both year 2 and year 3. CONCLUSION: There was a consistently small amount of osteitis on MRI in patients with early axSpA compared with baseline values, and only a very low rate of new-onset osteitis was found during 3 years of continuous treatment with ETN. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT00844142.
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Antirreumáticos/uso terapéutico , Inmunoglobulina G/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Adulto , Etanercept , Femenino , Estudios de Seguimiento , Humanos , Cuidados a Largo Plazo , Imagen por Resonancia Magnética , Masculino , Espondilitis/patología , Espondilitis/prevención & control , Espondilitis Anquilosante/patologíaRESUMEN
OBJECTIVE: To compare the 24-month course of health-related quality of life (HRQoL) in patients with long-standing RA treated with a conventional synthetic (cs) or a first, second or third biologic (b) DMARD in daily rheumatological care. METHODS: Patients enrolled in the German biologics register RABBIT who were observed over at least 12 months were stratified according to the nth bDMARD started at enrolment. HRQoL was captured by the SF36 health survey. Within strata of sequential bDMARD therapy, we examined patients' HRQoL at baseline and at follow-ups in comparison with the general population, the 24-month course of HRQoL of different bDMARDs and the proportion of patients exceeding the minimal detectable improvement of physical and mental health sum scores. RESULTS: All patients reported remarkably lower scores of physical and mental health than the general population at baseline and month 12. In each stratum of sequential bDMARD therapy, patients improved significantly by month 12 and remained stable until month 24. The improvement of HRQoL was not attributable to a particular bDMARD. The following proportions of patients exceeded the minimal detectable improvement of at least 17.85 Physical Component Scale scores or 22.18 Mental Component Scale score points: csDMARD (n = 1113) 31.1%/22.3%, first bDMARD (n = 1352) 39.9%/29.7%, second bDMARD (n = 730) 37.3%/26.2% and third bDMARD (n = 680) 34.2%/30.9%. CONCLUSION: Lasting improvement of both physical and mental health is achievable even for severely affected RA patients with a history of more than one bDMARD failure. Nevertheless, impairment of HRQoL in RA patients is enormous compared with the general population.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/psicología , Productos Biológicos/uso terapéutico , Calidad de Vida/psicología , Sistema de Registros , Adulto , Anciano , Artritis Reumatoide/epidemiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Encuestas Epidemiológicas , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and collate information on the availability of potential confounders within these registers. METHODS: Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co-morbidities, were collected and compared across 14 European bDMARD registers. RESULTS: A total of 5320 patients were included. Half the registers had restricted recruitment to certain bDMARDs during the study year. All registers` collected data on age, gender, disease duration, seropositivity for IgM-RF and 28-joint DAS (DAS28). The mean DAS28 ranged from 4.2 to 6.6 and the mean HAQ from 0.8 to 1.9. Current smoking ranged from 9% to 34%. Nine registers reported co-morbidities with varying prevalence. CONCLUSION: In addition to demonstrating European-wide collaboration across rheumatology bDMARD registers, this assessment identified differences in prescribing patterns, recruitment strategies and data items collected. These differences need to be considered when applying strategies for combined analysis. The lack of a common data model across Europe calls for further work to harmonize data collection across registers.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Grupos Diagnósticos Relacionados , Sistema de Registros/estadística & datos numéricos , Adulto , Estudios Transversales , Europa (Continente) , Humanos , Estadística como AsuntoRESUMEN
OBJECTIVE: Compare the radiographic progression of ankylosing spondylitis (AS) patients treated with infliximab (INF) versus historical controls (Herne cohort, HC) never treated with tumour necrosis factor (TNF)-blockers over 8 years. METHODS: Patients were selected based on the availability of lateral cervical and lumbar radiographs at baseline (BL) and after 8 years. Radiographs were scored by two blinded readers using modified Stokes AS spinal score (mSASSS). Mixed linear models were applied to compare radiographic progression between cohorts after adjustment for baseline status. RESULTS: Patients in INF (n=22) and HC (n=34) did not differ in the mSASSS status: 13.2 ± 17.6 in INF versus 14.2 ± 13.8 in HC (p=0.254). Both showed progression at 8 years: mean mSASSS 20.2 ± 21.4 in INF and 25.9 ± 17.8 in HC. After adjustment for baseline damage the mean mSASSS (SEM) at 8 years was 21.0 (1.4) in INF and 25.5 (1.1) HC (p=0.047). The mean mSASSS difference was similar in the groups between baseline and 4 years but was more pronounced in HC between 4 and 8 years (p=0.03 between groups). The mean number of syndesmophytes, although similar at baseline, differed significantly at 8 years: 1.0 ± 0.6 new syndesmophytes/patient in INF versus 2.7 ± 0.8 in HC (p=0.007). Adjustment for age, symptom duration, HLA-B27, Bath AS disease activity index and Bath AS function index at baseline had no influence. CONCLUSIONS: Despite limitations of patient numbers and retrospective study design, these data show increase in new bone formation in both patients treated with anti-TNF and those who did not. However, since there was even less bone formation in the INF treated group after 8 years, these data argue against a major role for the TNF-brake hypothesis.
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Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Osteogénesis/efectos de los fármacos , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/farmacología , Antirreumáticos/administración & dosificación , Antirreumáticos/farmacología , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/fisiopatología , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Infliximab , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/fisiopatología , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Radiografía , Estudios Retrospectivos , Método Simple Ciego , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/fisiopatología , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate efficacy and safety of ustekinumab in patients with ankylosing spondylitis (AS). METHODS: In this prospective, open-label, single-arm, proof-of-concept clinical trial (ClinicalTrials.gov identifier NCT01330901), ustekinumab in a dose of 90 mg was administered subcutaneously at baseline, week 4 and week 16 in 20 patients with active AS. Eligible patients were required to have a diagnosis of AS according to the modified New York criteria and an active disease defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4 despite previous non-steroidal anti-inflammatory drug (NSAID) treatment. The primary study endpoint was the proportion of patients reached the Assessment of SpondyloArthritis International Society 40 (ASAS40) response at week 24. RESULTS: At week 24, ASAS40 response was reached by 65% of the patients. ASAS20, ASAS5/6 and ASAS partial remission were observed in 75%, 50% and 30% of the patients, respectively. A ≥50% improvement of the BASDAI (BASDAI50) occurred in 55% of the patients. A total of 50% and 20% of the patients achieved the AS Disease Activity Score (ASDAS) clinically important improvement and major improvement, respectively. At week 24, 35% of the patients had an ASDAS inactive disease (ASDAS <1.3). Significant improvement of other patient-reported outcome parameters and active inflammation as detected by MRI as well as significant reduction of NSAIDs intake occurred during the treatment. Clinical response correlated with reduction of active inflammation on MRI and of serum C reactive protein level. Overall, ustekinumab was well tolerated. CONCLUSIONS: In this prospective, open-label, proof-of-concept clinical trial, ustekinumab treatment was associated with a reduction of signs and symptoms in active AS and was well tolerated.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Inmunosupresores/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Estudios Prospectivos , Espondilitis Anquilosante/patología , Factores de Tiempo , Resultado del Tratamiento , UstekinumabRESUMEN
OBJECTIVE: We assessed whether there is a difference to etanercept (ETA) treatment in patients with ankylosing spondylitis (AS) compared with non-radiographic axial SpA (nr-axSpA) patients with a disease duration <5 years. METHOD: AS (n=20) and nr-axSpA (n=20) patients who were treated with ETA for 1 year were compared for differences in baseline data and treatment effect. Clinical, laboratory and MRI of sacroiliac joints (SI-joints) and spine were analysed. RESULTS: At baseline, there were no significant differences between the 20 AS and the 20 nr-axSpA patients regarding age, disease duration, gender, HLA-B27 and clinical disease activity in terms of Bath AS Disease Activity Index (BASDAI), C-reactive protein and MRI SI-joint and spine scores in the AS compared with the nr-axSpA group. After 1 year of treatment with ETA the treatment effect was similarly good in AS and nr-axSpA (reduction of BASDAI by 3.3 (95% CI 2.2 to 3.8) vs 3.6 (95% CI 2.8 to 4.4) and reduction of AS Disease Activity Score by 1.8 (95% CI 1.5 to 2.2) vs 1.8 (95% CI 1.5 to 2.1), respectively. CONCLUSIONS: The response rate to TNF-blockers does not differ between AS and nr-axSpA if the baseline data regarding symptom duration and disease activity are similar for the two groups.