RESUMEN
OBJECTIVES: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). METHODS: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). RESULTS: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. CONCLUSIONS: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. TRIAL REGISTRATION NUMBER: NCT02339441.
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Esclerodermia Difusa/diagnóstico , Índice de Severidad de la Enfermedad , Pruebas Cutáneas/estadística & datos numéricos , Adulto , Área Bajo la Curva , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Humanos , Modelos Logísticos , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , ARN Polimerasa III/análisis , Curva ROC , Esclerodermia Difusa/enzimología , Esclerodermia Difusa/patología , Piel/patologíaRESUMEN
OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. METHODS: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24â months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. RESULTS: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24â months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12â months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24â months. CONCLUSIONS: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12â months and that better treatments are needed. TRIAL REGISTRATION NUMBER: NCT02339441.
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Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Metotrexato/uso terapéutico , Ácido Micofenólico/uso terapéutico , Esclerodermia Difusa/tratamiento farmacológico , Adulto , Anticuerpos Antinucleares/inmunología , Autoanticuerpos/inmunología , Estudios de Cohortes , ADN-Topoisomerasas de Tipo I , Intervención Médica Temprana , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Nucleares/inmunología , Estudios Prospectivos , ARN Polimerasa III/inmunología , Esclerodermia Difusa/inmunología , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Tumour necrosis factor (TNF)-alpha inhibitors are beneficial for the treatment of rheumatoid arthritis (RA) in terms of reducing the risk of joint damage, improving physical function and improving quality of life. This Cochrane review is an update of a review of the treatment of RA with certolizumab pegol that was first published in 2011. OBJECTIVES: To assess the clinical benefits and harms of certolizumab pegol (CDP870) in patients with RA who have not responded well to conventional disease-modifying anti-rheumatic drugs (DMARDs). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 5), MEDLINE, EMBASE, Scopus, TOXLINE, Web of Knowledge; websites of the US Food and Drug Administration (FDA) and European Medicines Evaluation Agency (EMEA); reference lists of articles; and searched http/clinicaltrials.gov. The searches were updated from 2009 (date of last search for the original review) to 5 June 2014. SELECTION CRITERIA: Randomised controlled trials that compared certolizumab pegol with any other agent including placebo or methotrexate (MTX) in adult patients with active RA despite current or prior treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs), such as MTX. DATA COLLECTION AND ANALYSIS: Two authors independently assessed search results, trial quality and extracted data. Disagreements were resolved by discussion or referral to a third author. MAIN RESULTS: Eleven trials were included in this update. Ten (4324 patients) were included in the pooled analysis for benefits, five more than previously, and 10 (3711 patients) in the pooled analysis for harms, four more trials (1930 patients) than previously. The duration of follow-up varied from 12 to 52 weeks and the range of doses of certolizumab pegol varied from 50 to 400 mg given subcutaneously (sc). In phase III trials, the control was placebo plus MTX in five trials and placebo in four trials. The risk of bias of the included studies was assessed as low but there may have been a risk of attrition bias.Statistically significant improvements were observed at 24 weeks with the approved dose of 200 mg certolizumab pegol every other week, in 1) American College of Rheumatology (ACR) 50% improvement: 27% absolute improvement (95% CI 20% to 33%), NNT of 4 (95% CI 3 to 8), risk ratio (RR) 3.80 (95% CI 2.42 to 5.95); 2) the Health Assessment Questionnaire (HAQ): -12% absolute improvement (95% CI -9% to -14%), NNT of 6 (95% CI 5 to 8), mean difference (MD) - 0.35 (95% CI -0.43 to -0.26) (scale 0 to 3); 3) Disease Activity Score (DAS) remission improvement: absolute improvement 11% (95% CI 8% to 15%), NNT of 9 (95% CI 4 to 20), RR 8.47 (95% CI 4.15-17.28); and 4) radiological changes: erosion score (ES) absolute improvement -0.29% (95% CI -0.42% to -0.17%), NNT of 6 (95% CI 4 to 10), MD -0.67 (95% CI -0.96 to -0.38) (scale 0 to 230). Serious adverse events were statistically significantly more frequent for certolizumab pegol (200 mg every other week) with an absolute rate difference of 4% (95% CI 2% to 6%), NNTH of 32 (95% CI 17 to 88), Peto odds ratio (OR) 1.77 (95% CI 1.27 to 2.46). There was a statistically significant increase in all withdrawals in the placebo groups (for all doses and all follow-ups) with an absolute rate difference of -34% (95% CI -18% to -50%), NNTH of 4 (95% CI 3 to 5), NNTH of 4 (95% CI 3 to 5), RR 0.42 (95% CI 0.36 to 0.50); and there was a statistically significant increase in all withdrawals due to adverse events in the certolizumab groups (for all doses and all follow-up) with an absolute rate difference of 2% (95% CI 1% to 3%), NNTH of 55 (95% CI 27 to 238), Peto OR 1.66 (95% CI 1.15 to 2.37).The risk of bias was low and the quality of evidence was downgraded to moderate because of high rates of dropouts (> 20%) in most of the trials. We did not find any problems with inconsistency, indirectness, imprecision or publication bias. AUTHORS' CONCLUSIONS: The results and conclusions did not change from the previous review. There is moderate-level evidence from randomised controlled trials that certolizumab pegol alone or combined with methotrexate is beneficial in the treatment of RA. Adverse events were more frequent with active treatment. We found a potential risk of serious adverse events.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Polietilenglicoles/uso terapéutico , Adulto , Anticuerpos Monoclonales Humanizados , Humanos , Metotrexato/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
People with long-term conditions are frequent visitors to outpatient clinics. In order that they get the best out of their visits, the health professionals taking care of them need to understand their experiences and work towards service improvements. A survey of 3 clinics (HIV, rheumatology, diabetes) was undertaken using a set of three simple, open questions. A total of 147 people responded that, above all, care, attention, friendliness and efficiency were their most valued experiences. Shorter waiting times and cheaper car parking came up most frequently as sources of dissatisfaction. The study concludes that there were no distinct differences in the experiences of the patients in each clinic. All care needs were relatively simple and, on the whole, met.
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Instituciones de Atención Ambulatoria/normas , Diabetes Mellitus/enfermería , Infecciones por VIH/enfermería , Satisfacción del Paciente/estadística & datos numéricos , Enfermedades Reumáticas/enfermería , Adulto , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria/organización & administración , Diabetes Mellitus/terapia , Infecciones por VIH/terapia , Humanos , Persona de Mediana Edad , Evaluación de Programas y Proyectos de Salud , Enfermedades Reumáticas/terapia , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVES: Early therapy improves outcomes in rheumatoid arthritis (RA). It is therefore important to improve predictive algorithms for RA in early disease. This study evaluated musculoskeletal ultrasound, a sensitive tool for the detection of synovitis and erosions, as a predictor of outcome in very early synovitis. METHODS: 58 patients with clinically apparent synovitis of at least one joint and symptom duration of ≤3 months underwent clinical, laboratory, radiographic and 38 joint ultrasound assessments and were followed prospectively for 18 months, determining outcome by 1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism criteria. Sensitivity and specificity for 1987 RA criteria were determined for ultrasound variables and logistic regression models were then fitted to evaluate predictive ability over and above the Leiden rule. RESULTS: 16 patients resolved, 13 developed non-RA persistent disease and 29 developed RA by 1987 criteria. Ultrasound demonstrated subclinical wrist, elbow, knee, ankle and metatarsophalangeal joint involvement in patients developing RA. Large joint and proximal interphalangeal joint ultrasound variables had poor predictive ability, whereas ultrasound erosions lacked specificity. Regression analysis demonstrated that greyscale wrist and metacarpophalangeal joint involvement, and power Doppler involvement of metatarsophalangeal joints provided independently predictive data. Global ultrasound counts were inferior to minimal power Doppler counts, which significantly improved area under the curve values from 0.905 to 0.962 combined with the Leiden rule. CONCLUSION: In a longitudinal study, extended ultrasound joint evaluation significantly increased detection of joint involvement in all regions and outcome groups. Greyscale and power Doppler scanning of metacarpophalangeal joints, wrists and metatarsophalangeal joints provides the optimum minimal ultrasound data to improve on clinical predictive models for RA.
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Artritis Reumatoide/diagnóstico por imagen , Sinovitis/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/patología , Diagnóstico Precoz , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Articulación Metacarpofalángica/diagnóstico por imagen , Articulación Metatarsofalángica/diagnóstico por imagen , Persona de Mediana Edad , Sinovitis/etiología , Sinovitis/patología , Ultrasonografía Doppler , Articulación de la Muñeca/diagnóstico por imagen , Adulto JovenRESUMEN
Modelling cost-effectiveness of new drugs for RA has become increasingly prevalent and sophisticated. This situation has arisen largely because regulatory agencies, such as the National Institute for Health and Clinical Excellence, have demanded models from industry and have commissioned independent models. Many technical aspects of health economic models have converged-yet the results of models differ greatly. These differences can be accounted for in large part by differences in assumptions about the nature of patients likely to be treated; likely treatment sequences; likely responses to treatment; likely continuation on drug and likely disease progression, in particular. Such parameters cannot be fixed and evolve with changing practice and are ideally captured by contemporary data. Importantly, data from the local setting to which a health economic problem is applied are necessary, but in the absence of ideal sources, for the many contributions needed, considerable differences in opinion and biases are commonplace. In the final analysis, all models are just that, models, and as such an approximation of real life. Thus, although considerable heat is generated during debates about model parameters, model outputs may just yield sufficient light for regulatory agencies allocating resources.
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Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/economía , Modelos Econométricos , Antirreumáticos/efectos adversos , Antirreumáticos/economía , Antirreumáticos/uso terapéutico , Productos Biológicos/efectos adversos , Productos Biológicos/economía , Productos Biológicos/uso terapéutico , Progresión de la Enfermedad , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: Foot orthoses, which are specially moulded devices fitted into footwear, are one of the treatment options for patellofemoral or anterior knee pain. OBJECTIVES: To assess the effects of foot orthoses for managing patellofemoral pain in adults. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group's Specialised Register (March 2010), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 1), MEDLINE (1950 to March 2010), EMBASE (1980 to 2010 Week 11), CINAHL (1937 to March 2010), trial registers, reference lists and grey literature. No language restriction was applied. SELECTION CRITERIA: We included randomised or quasi-randomised clinical studies that compared foot orthoses with flat insoles or another physical therapy intervention. The primary outcomes were knee pain and knee function. DATA COLLECTION AND ANALYSIS: Two authors independently selected eligible trials, assessed methodological quality and performed data extraction. We calculated risk ratios and 95% confidence intervals for dichotomous variables, and mean differences with 95% confidence intervals for continuous variables. We pooled data using the fixed-effect model. MAIN RESULTS: Two trials with a total of 210 participants were included. Both trials were at some risk of performance bias. One trial had four intervention groups and the other had three. One trial found that foot orthoses when compared with flat insoles (control group) had better results at six weeks in knee pain (participants with global improvement: risk ratio 1.48, 95% confidence interval 1.11 to 1.99), but not at one year follow-up. Participants in the orthoses group reported significantly more minor adverse effects (e.g. rubbing, blistering) compared with the flat insole group (risk ratio 1.87, 95% confidence intervaI 1.21 to 2.91). Both trials in their comparisons of orthoses plus physiotherapy versus physiotherapy alone found no statistically significant differences between the two intervention groups in knee pain or function. Results for knee pain outcomes did not show significant differences between foot orthoses versus physiotherapy. Although participants in the physiotherapy group had consistently better results for the functional index questionnaire, the clinical relevance of these results is uncertain. AUTHORS' CONCLUSIONS: While not robust, the available evidence does not reveal any clear advantage of foot orthoses over simple insoles or physiotherapy for patellofemoral pain. While foot orthoses may help relieve knee pain over the short term, the benefit may be marginal. Patients treated with orthoses are more likely to complain of mild adverse effects and discomfort.
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Aparatos Ortopédicos , Manejo del Dolor , Articulación Patelofemoral , Adulto , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: TNF-alpha inhibitors have been shown to reduce the risk of joint damage and improve physical function and quality of life in people with rheumatoid arthritis (RA). This is the first Cochrane review of certolizumab pegol, a new TNF-alpha inhibitor. OBJECTIVES: To assess the effectiveness and safety of certolizumab pegol (CDP870) in patients with RA who have not responded well to conventional disease modifying anti-rheumatic drugs (DMARDs). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to November 2009), EMBASE (1966 to November 2009), Scopus (January 2004 to November 2009), TOXLINE (until November 2009), Web of Knowledge (until November 2009); websites of the US Food and Drug Administration (FDA) and European Medicines Evaluation Agency (EMEA) (until November 2009), and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials that compared certolizumab pegol with any other agent including placebo or methotrexate (MTX) in adult RA patients with active rheumatoid arthritis despite current or prior treatment with conventional DMARDs, such as methotrexate (MTX). DATA COLLECTION AND ANALYSIS: Two authors independently assessed search results, trial quality and extracted data. MAIN RESULTS: Five trials were included. We included in the analysis 2394 people for effectiveness and 2094 people for safety. The duration of follow-up was from 12 to 52 weeks, and the range of doses of certolizumab pegol were from 50 to 400 mg subcutaneously (sc). In three trials the control was placebo plus methotrexate (MTX) and in two trials it was just placebo. Significant improvements were observed at 24 weeks with the approved dose of 200 mg certolizumab pegol: American College of Rheumatology (ACR) 50% improvement: risk ratio (RR) 6.01 (95% CI 3.84 to 9.40) with an absolute benefit of 29% (95% CI 25% to 34%), number needed to treat to benefit (NNTB) of 4 (3 to 5) and the Health Assessment Questionnaire (HAQ) mean difference (MD) - 0.39 (95% CI -0.45 to -0.32) (scale 0 to 3). At 52 weeks the results were quite similar: ACR 50% improvement RR 5.27 (95% CI 3.19 to 8.71), HAQ mean difference (MD) - 0.42 (95% CI -0.52 to -0.32). Serious adverse events were more frequent for certolizumab pegol 200 mg, Peto OR 2.02 (95% CI 1.24 to 3.30). The most common adverse events with certolizumab pegol 200 mg were: upper respiratory tract infections, Peto OR 2.21 (95% CI 1.15 to 4.25); hypertension, Peto OR 2.81 (95% CI 1.38 to 5.75); and nasopharyngitis, Peto OR 2.71 (95% CI 1.30 to 5.66). AUTHORS' CONCLUSIONS: With an overall high grade of evidence this review revealed an improvement of clinical results (ACR50, 28 joint disease activity score (DAS-28) remission and HAQ scores) with certolizumab pegol. Adverse events were more frequent with certolizumab; there was a statistically significant increase in the number of serious adverse events, infections and hypertension.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Polietilenglicoles/uso terapéutico , Adulto , Anticuerpos Monoclonales Humanizados , Certolizumab Pegol , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Many people attending rheumatology clinics use analgesics and non-steroidal anti-inflammatories for persistent musculoskeletal pain. Guidelines for pain management recommend regular and pre-emptive use of analgesics to reduce the impact of pain. Clinical experience indicates that analgesics are often not used in this way. Studies exploring use of analgesics in arthritis have historically measured adherence to such medication. Here we examine patterns of analgesic use and their relationships to pain, self-efficacy and demographic factors. METHODS: Consecutive patients were approached in a hospital rheumatology out-patient clinic. Pattern of analgesic use was assessed by response to statements such as 'I always take my tablets every day.' Pain and self-efficacy (SE) were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Arthritis Self-Efficacy Scale (ASES). Influence of factors on pain level and regularity of analgesic use were investigated using linear regression. Differences in pain between those agreeing and disagreeing with statements regarding analgesic use were assessed using t-tests. RESULTS: 218 patients (85% of attendees) completed the study. Six (2.8%) patients reported no current pain, 26 (12.3%) slight, 100 (47.4%) moderate, 62 (29.4%) severe and 17 (8.1%) extreme pain. In multiple linear regression self efficacy and regularity of analgesic use were significant (p < 0.01) with lower self efficacy and more regular use of analgesics associated with more pain.Low SE was associated with greater pain: 40 (41.7%) people with low SE reported severe pain versus 22 (18.3%) people with high SE, p < 0.001. Patients in greater pain were significantly more likely to take analgesics regularly; 13 (77%) of those in extreme pain reported always taking their analgesics every day, versus 9 (35%) in slight pain. Many patients, including 46% of those in severe pain, adjusted analgesic use to current pain level. In simple linear regression, pain was the only variable significantly associated with regularity of analgesic use: higher levels of pain corresponded to more regular analgesic use (p = 0.003). CONCLUSION: Our study confirms that there is a strong inverse relationship between self-efficacy and pain severity. Analgesics are often used irregularly by people with arthritis, including some reporting severe pain.
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Analgésicos/uso terapéutico , Artritis/tratamiento farmacológico , Cumplimiento de la Medicación , Servicio Ambulatorio en Hospital , Dolor/tratamiento farmacológico , Reumatología , Autoeficacia , Adulto , Anciano , Artritis/complicaciones , Artritis/etnología , Artritis/psicología , Estudios Transversales , Etnicidad , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Dolor/diagnóstico , Dolor/etnología , Dolor/etiología , Dolor/psicología , Dimensión del Dolor , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Spontaneous reporting systems for adverse drug reactions (ADRs) are handicapped by under-reporting and limited detail on individual cases. We report an investigation from a local surveillance for serious adverse drug reactions associated with disease modifying anti-rheumatic drugs that was triggered by the occurrence of liver failure in two of our patients. METHODS: Serious ADR reports have been solicited from local clinicians by regular postcards over the past seven years. Patients', who had hepatotoxicity on sulfasalazine and met a definition of a serious ADR, were identified. Two clinicians reviewed structured case reports and assessed causality by consensus and by using a causality assessment instrument. The likely frequency of hepatotoxicity with sulfasalazine was estimated by making a series of conservative assumptions. RESULTS: Ten cases were identified: eight occurred during surveillance. Eight patients were hospitalised, two in hepatic failure - one died after a liver transplant. All but one event occurred within 6 weeks of treatment. Seven patients had a skin rash, three eosinophilia and one interstitial nephritis. Five patients were of Black British of African or Caribbean descent. Liver enzymes showed a hepatocellular pattern in four cases and a mixed pattern in six. Drug-related hepatotoxicity was judged probable or highly probable in 8 patients. The likely frequency of serious hepatotoxicity with sulfasalazine was estimated at 0.4% of treated patients. CONCLUSION: Serious hepatotoxicity associated with sulfasalazine appears to be under-appreciated and intensive monitoring and vigilance in the first 6 weeks of treatment is especially important.
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Antiinflamatorios no Esteroideos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas , Sulfasalazina/efectos adversos , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Artritis Reumatoide/epidemiología , Población Negra/estadística & datos numéricos , Inglaterra/epidemiología , Femenino , Humanos , Hepatopatías/etnología , Hepatopatías/mortalidad , Fallo Hepático/inducido químicamente , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
Background: It is widely believed that patients bearing auto-antibodies to histidyl tRNA synthetase (anti-Jo-1) very likely have a connective tissue disease including myositis and interstitial lung disease. The value of positive tests in low disease prevalence settings such as those tested in routine care is unknown. We sought to determine the value of anti-Jo-1 auto-antibodies in routine practice. Methods: Our study was a nested case control study within a retrospective cohort of all patients tested for anti-ENA our hospital, from any hospital department, between January 2013 and December 2014. Data was extracted from electronic records of anti-Jo-1 positive patients and randomly selected ENA negative patients (ratio of 1:2), allowing for a minimum follow up of at least 12 months after first testing. Results: 4009 samples (3581 patients) were tested. Anti-ENA was positive in 616 (17.2%) patients, 40 (1.1%) were anti-Jo-1 positive. Repeat ENA testing was done for 350/3581 (9.8%) patients (428 of 4009 (10.7%) samples) and in 7/40 (17.5%) of anti-Jo-1 positive patients. The median interval between the first and second request was 124 days (inter-quartile range 233 days). The frequencies of interstitial lung disease (ILD), myositis and Raynaud's were comparable for anti-Jo-1 positive patients (n=40) and 80 randomly selected ENA negative controls. Positive tests led to additional diagnostic testing in the absence of clinical disease. Sensitivity of Jo-1 for ILD was 50% (CI 19-81%), specificity 68% (CI 59-77%), positive predictive value 12.5% (CI 4 to 27%) and negative predictive value 93.8% (CI 86-98%). Of 10 (25%) patients with high anti-Jo1 levels, 3 had ILD, one myositis and two a malignancy (disseminated melanoma and CML). Conclusion: Anti-Jo-1 is uncommon in a heterogenous hospital population and is only weakly predictive for ILD. Repeated test requests were common and potentially unnecessary indicating that controls over repeat requests could yield significant cost savings.
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BACKGROUND: Hydrotherapy is highly valued by people with rheumatoid arthritis yet few studies have compared the benefits of exercises in heated water against exercises on land. In particular, data on quality of life is rarely reported. This is especially important because patients treated with hydrotherapy often report an enhanced sense of well-being. We report a randomised controlled trial in which we compared the effects of hydrotherapy with exercises on land on overall response to treatment, physical function and quality of life in patients with rheumatoid arthritis. METHODS: One hundred and fifteen patients with RA were randomised to receive a weekly 30-minute session of hydrotherapy or similar exercises on land for 6 weeks. Our primary outcome was a self-rated global impression of change--a measure of treatment effect on a 7-point scale ranging from 1(very much worse) to 7 (very much better) assessed immediately on completion of treatment. Secondary outcomes including EuroQol health related quality of life, EuroQol health status valuation, HAQ, 10 metre walk time and pain scores were collected at baseline, after treatment and 3 months later. Binary outcomes were analysed by Fisher's exact test and continuous variables by Wilcoxon or Mann-Whitney tests. RESULTS: Baseline characteristics of the two groups were comparable. Significantly more patients treated with hydrotherapy (40/46, 87%) were much better or very much better than the patients treated with land exercise (19/40, 47.5%), p < 0.001 Fisher's exact test. Eleven patients allocated land exercise failed to complete treatment compared with 4 patients allocated hydrotherapy (p = 0.09). Sensitivity analyses confirmed an advantage for hydrotherapy if we assumed non-completers would all not have responded (response rates 70% versus 38%; p < 0.001) or if we assumed that non-completers would have had the same response as completers (response rates 82% versus 55% p = 0.002). Ten metre walk time improved after treatment in both cases (median pre-treatment time for both groups combined 10.9 seconds, post-treatment 9.1 s, and 3 months later 9.6 s). There was however no difference between treatment groups. Similarly there were no significant differences between groups in terms of changes to HAQ, EQ-5D utility score, EQ VAS and pain VAS. CONCLUSION: Patients with RA treated with hydrotherapy are more likely to report feeling much better or very much better than those treated with land exercises immediately on completion of the treatment programme. This perceived benefit was not reflected by differences between groups in 10-metre walk times, functional scores, quality of life measures and pain scores.
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Artritis Reumatoide/rehabilitación , Terapia por Ejercicio , Hidroterapia , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/psicología , Artritis Reumatoide/terapia , Terapia Combinada , Femenino , Calor/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Calidad de Vida , Autoevaluación (Psicología) , Resultado del TratamientoRESUMEN
Temporal artery aneurysm is a rare cause of temporal artery swelling in the absence of preceding trauma. Vasculitis other than giant cell arteritis, such as eosinophilic granulomatosis with polyangiitis, should be considered in such cases and a careful assessment of other medium-sized arteries undertaken.
RESUMEN
A 60-year-old man presented with cutaneous vasculitis, leucopenia and psoriasis. He was treated initially with ciclosporin A. On withdrawal of ciclosporin, due to inadequate improvement of cutaneous vasculitis, he developed psoriatic arthritis. Worsening neutropenia and pancytopenia, believed to be immune mediated, developed. He was treated with prednisolone, methotrexate and adalimumab but developed pneumocystis pneumonia. Leucocyte levels improved markedly with granulocyte colony-stimulating factor (G-CSF). However, whilst being treated with G-CSF his condition deteriorated. He developed gastrointestinal and neurological symptoms and progressive weight loss. Diagnosis was delayed, but eventually polyarteritis nodosa was diagnosed and he was treated with cyclophosphamide. The patient improved initially but died from small bowel perforation due to vasculitis. Evidence showing a temporal association of his deterioration with use of G-CSF is shown. The use of G-CSF in patients with autoimmune conditions including vasculitis should be undertaken with great caution.
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INTRODUCTION: Biologic therapies are efficacious but costly. A number of health economic models have been developed to determine the most cost-effective way of using them in the treatment pathway. These models have produced conflicting results, driven by differences in assumptions, model structure, and data, which undermine the credibility of funding decisions based on modeling studies. A Consensus Working Party met to discuss recommendations and approaches for future models of biologic therapies. METHODS: Our working party consisted of clinical specialists, modelers, and policy makers. Two 1-day meetings were held for members to arrive at consensus positions on model structure, assumptions, and appropriate data sources. These views were guided by clinical aspects of rheumatoid and psoriatic arthritis and the principles of evidence-based medicine. Where opinions differed, we sought to identify a research agenda that would generate the evidence needed to reach consensus. RESULTS: We gained consensus in four areas of model development: initial response to treatment; long-term disease progression; lifetime costs and benefits; and model structure. Consensus was also achieved on some key parameters such as choices of outcome measures, methods for extrapolation beyond trial data, and treatment switching. A research agenda to support further consensus was also identified. CONCLUSION: Consensus guidance that fully reflects current evidence and clinical understanding was gained successfully. In addition, research needs have been identified. Such guidance can be updated as evidence develops and policy questions change and need not be prescriptive as long as deviations from consensus are clearly explained and justified. FUNDING: Arthritis Research UK and the UK Medical Research Council Network of Hubs for Trials Methodology Research.
RESUMEN
BACKGROUND: Serious adverse events may occur from the use of disease modifying antirheumatic drugs (DMARDs) used to treat rheumatoid arthritis. We describe preliminary data from a regional surveillance scheme. Our aims were to identify a broad range of potential adverse events, to identify deficiencies in care and examine the management of common events in order to improve care. METHODS: Adverse events were sought by regular postcards to clinicians in the West Midlands region of the UK. Each reported case was carefully described and the opinions of at least three peer-reviewers were sought on cause-effect relationships, the potential for prevention and the appropriateness of management. RESULTS: Forty-four serious adverse events associated with DMARD use were reported between December 1999 and October 2001. Events included eight patients with malignancies, two with pancytopenia taking methotrexate, three with septic arthritis, and two with septicaemias. Fifteen cases have been peer-reviewed in detail, so far. At least two reviewers thought that eight events were related to DMARD use and that two were preventable. Agreement between pairs of reviewers was fair or moderate (weighted kappa 0.23-0.5). DISCUSSION: We have successfully implemented a regional system for identifying potential drug-related serious adverse events. A diverse range of potential drug-related events has been seen. Early analyses have highlighted the difficulties of determining cause-effect relationships between a drug and an event.
Asunto(s)
Antirreumáticos/efectos adversos , Monitoreo de Drogas/métodos , Antirreumáticos/uso terapéutico , Artritis Infecciosa/inducido químicamente , Azatioprina/efectos adversos , Azatioprina/uso terapéutico , Humanos , Hipopotasemia/inducido químicamente , Neoplasias Pulmonares/inducido químicamente , Linfoma no Hodgkin/inducido químicamente , Masculino , Metotrexato/efectos adversos , Metotrexato/uso terapéutico , Neutropenia/inducido químicamente , Pancitopenia/inducido químicamente , Neumonía/inducido químicamente , Vigilancia de Productos Comercializados/métodos , Neoplasias de la Próstata/inducido químicamente , Sepsis/inducido químicamente , Sulfasalazina/efectos adversos , Sulfasalazina/uso terapéutico , Reino UnidoRESUMEN
OBJECTIVE: To compare adalimumab versus etanercept in patients with active rheumatoid arthritis (RA) to test the hypothesis that adalimumab was not inferior to etanercept in terms of drug continuation by a margin of 15% after 52 weeks of treatment. DESIGN: Pragmatic, randomised, parallel group, multicentre, unblinded and non-inferiority trial. Randomisation stratified by baseline use of methotrexate. PARTICIPANTS: 125 adults with active RA despite treatment with two disease-modifying drugs (DMARDs), including methotrexate randomised (1 : 1) to adalimumab 40 mg alternate weeks or etanercept 50 mg weekly, added to existing medication. MEASUREMENTS: The primary outcome was proportion of patients continuing treatment after 52 weeks. Secondary outcomes included: disease activity score using 28 joints (DAS28), treatment satisfaction (TSQM V.2), health status (Euroqol-5D), drug toxicity and persistence with therapy after 2 years. RESULTS: Persistence with therapy was 65% for adalimumab versus 56.7% for etanercept (one-sided 95% CI for proportion still taking adalimumab minus proportion on etanercept ≥-7.9%); demonstrating non-inferiority at the 15% margin. After 2 years these figures were: adalimumab 58.3% and etanecept 43.3% (CI ≥-1.7%). The proportion of good, moderate and non-responders based on DAS28-C reactive protein, after 52 weeks, were 26.3%, 33.3% and 40.4%, respectively, for adalimumab versus 16.7%, 31.7% and 51.7%, respectively, for etanercept (p=0.158). Baseline median EQ-5D scores improved from 0.52 to 0.69 for adalimumab and from 0.52 to 0.64 for etanercept (p=0.046) after 52 weeks. Global satisfaction, effectiveness, side effects and convenience scores based on the TSQM were similar for both drugs. Fourteen serious adverse events occurred including two deaths from myocardial infarction, one patient with ovarian cancer and one with acute myeloid leukaemia. CONCLUSIONS: Clinicians choosing a first tumour necrosis factor inhibitor for active RA, despite trying two DMARDs including methotrexate, may choose either adalimumab or etanercept in the knowledge that these drugs are similarly effective. CLINICAL TRIAL REGISTRATION NUMBER: EU Clinical Trials Register 2006-006275-21/GB.