Dietary supplements for chronic gout.

BACKGROUND: Dietary supplements are frequently used for the treatment of several medical conditions, both prescribed by physicians or self administered. However, evidence of benefit and safety of these supplements is usually limited or absent. OBJECTIVES: To assess the efficacy and safety of dietary supplementation for people with chronic gout. SEARCH METHODS: We updated the original search by searching CENTRAL, MEDLINE, Embase, CINAHL, and four trials registers (August 2020). We applied no date or language restrictions. We also handsearched the abstracts from the 2010 to 2019 American College of Rheumatology and European League against Rheumatism conferences, and checked the references of all included studies. SELECTION CRITERIA: We considered all published randomised controlled trials (RCTs) or quasi-RCTs that compared dietary supplements with no supplements, placebo, another supplement, or pharmacological agents for adults with chronic gout for inclusion. Dietary supplements included, but were not limited to, amino acids, antioxidants, essential minerals, polyunsaturated fatty acids, prebiotic agents, probiotic agents, and vitamins. The major outcomes were acute gout flares, study withdrawal due to adverse events (AEs), serum uric acid (sUA) reduction, joint pain reduction, participant global assessment, total number of AEs, and tophus regression. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Two previously included RCTs (160 participants) met our inclusion criteria; we did not identify any new trials for this update. As these two trials evaluated different diet supplements (enriched skim milk powder (SMP) and vitamin C) with different outcomes (gout flare prevention for enriched SMP, and sUA reduction for vitamin C), we reported the results separately. One trial (120 participants), at unclear risk of selection and detection bias, compared SMP enriched with glycomacropeptides (GMP) with un-enriched SMP, and with lactose, over three months. Participants were predominantly men, aged in their 50s, who had severe gout. The results for all major outcomes were imprecise, except for pain. None of the results were clinically significant. The frequency of acute gout attacks, measured as the number of flares per month, decreased in all three groups over the three-month study period. The effects of enriched SMP (SMP/GMP/G600) compared with the combined control groups (SMP and lactose powder) at three months in terms of mean number of gout flares per month were not clinically significant (mean (standard deviation (SD)) flares per month: 0.49 (1.52) in SMP/GMP/G60 group versus 0.70 (1.28) in the control groups; absolute risk difference: mean difference (MD) -0.21 flares per month, 95% confidence interval (CI) -0.76 to 0.34; low-quality evidence). The number of withdrawals due to adverse effects was similar between groups (7/40 in SMP/GMP/G600 group versus 11/80 in control groups; (risk ratio (RR) 1.27, 95% CI 0.53 to 3.03); there were 4% more withdrawals in the SMP/lactose groups (10% fewer to 18% more; low-quality evidence). Serum uric acid reduction was similar across groups (mean (SD) -0.025 (0.067) mmol/L in SMP/GMP/G60 group versus -0.010 (0.069) in control groups; MD -0.01, 95% CI -0.04 to 0.01; low-quality evidence). Pain from self-reported gout flares (measured on a 10-point Likert scale) improved slightly more in the GMP/G600 SMP group compared with controls (mean (SD) -1.97 (2.28) in SMP/GMP/G600 group versus -0.94 (2.25) in control groups; MD -1.03, 95% CI -1.89 to -0.17). This was an absolute reduction of 10% (95% CI 20% to 1% reduction; low-quality evidence), which may not be of clinical relevance. The risk of adverse events was similar between groups (19/40 in SMP/GMP/G600 group versus 39/80 in control groups; RR 0.97, 95% CI 0.66 to 1.45); the absolute risk difference was 1% fewer adverse events (1% fewer to 2% more), low-quality evidence). Gastrointestinal events such as nausea, flatulence and diarrhoea were the most commonly reported adverse effects. Data for participant global assessment were not available for analysis; the study did not report tophus regression. One trial (40 participants), at high risk of selection, performance, and detection bias, compared vitamin C alone with allopurinol, and with allopurinol plus vitamin C, in a three-arm study. We only included data from the vitamin C versus allopurinol comparison in this review. Participants were predominantly middle-aged men, and their severity of gout was representative of gout in general. Allopurinol reduced sUA levels more than vitamin C (MD 0.10 mmol/L, 95% CI 0.06 to 0.15), low-quality evidence. The study reported no adverse events; none of the participants withdrew due to adverse events. The study did not assess the rate of gout attacks, joint pain reduction, participant global assessment, or tophus regression. AUTHORS' CONCLUSIONS: While dietary supplements may be widely used for gout, this review found no high-quality that supported or refuted the use of glycomacropeptide-enriched skim milk powder or vitamin C for adults with chronic gout.

2021 EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis.

BACKGROUND: An important but often insufficient aspect of care in people with inflammatory arthritis (IA) is empowering patients to acquire a good understanding of their disease and building their ability to deal effectively with the practical, physical and psychological impacts of it. Self-management skills can be helpful in this regard. OBJECTIVES: To develop recommendations for the implementation of self-management strategies in IA. METHODS: A multidisciplinary taskforce of 18 members from 11 European countries was convened. A systematic review and other supportive information (survey of healthcare professionals (HCPs) and patient organisations) were used to formulate the recommendations. RESULTS: Three overarching principles and nine recommendations were formulated. These focused on empowering patients to become active partners of the team and to take a more proactive role. The importance of patient education and key self-management interventions such as problem solving, goal setting and cognitive behavioural therapy were highlighted. Role of patient organisations and HCPs in promoting and signposting patients to available resources has been highlighted through the promotion of physical activity, lifestyle advice, support with mental health aspects and ability to remain at work. Digital healthcare is essential in supporting and optimising self-management and the HCPs need to be aware of available resources to signpost patients. CONCLUSION: These recommendations support the inclusion of self-management advice and resources in the routine management of people with IA and aim to empower and support patients and encourage a more holistic, patient-centred approach to care which could result in improved patient experience of care and outcomes.

Adherence to subcutaneous biological therapies in patients with inflammatory rheumatic diseases and inflammatory bowel disease: a systematic review.

Aim: To assess adherence to subcutaneous biologicals in adults with inflammatory rheumatic diseases or inflammatory bowel disease and evaluate factors possibly associated with adherence. Materials & methods: Systematic searches were conducted of main databases from January 2000 to June 2019. Results: 41 articles (32 full papers and nine abstracts) were included in the review. Among studies which used a medication possession ratio threshold of ≥80% as the end point, adherence varied from 28.8 to 89.4%. Possible predictors of adherence were older age, professional or family member support, belief in medication necessity, lower concerns about medication and monthly versus weekly administration. Conclusion: Considerable variability in adherence rates across published studies reflects study heterogeneity and the absence of a 'gold standard' to measure adherence.

Development of a Tool to Measure the Clinical Response to Biologic Therapy in Uncontrolled Severe Asthma: The FEV1, Exacerbations, Oral Corticosteroids, Symptoms Score.

BACKGROUND: There is a lack of tools to quantify the response to monoclonal antibodies (mAbs) holistically in severe uncontrolled asthma patients. OBJECTIVE: To develop a valid score to assist specialists in this clinical context. METHODS: The score was developed in four subsequent phases: (1) elaboration of the theoretical model of the construct intended to be measured (response to mAbs); (2) definition and selection of items and measurement instruments by Delphi survey; (3) weight assignment of the selected items by multicriteria decision analysis using the Potentially All Pairwise RanKings of All Possible Alternatives methodology using the 1000minds software; and (4) face validity assessment of the obtained score. RESULTS: Four core items, with different levels of response for each, were selected: severe exacerbations, oral corticosteroid use, symptoms (evaluated by Asthma Control Test), and bronchial obstruction (assessed by FEV1 percent predicted). Severe exacerbations and oral corticosteroid maintenance dose were weighted most heavily (38% each), followed by symptoms (13%) and FEV1 (11%). Higher scores in the weighted system indicate a better response and the range of responses runs from 0 (worsening) to 100 (best possible response). Face validity was high (intraclass correlation coefficient of 0.86). CONCLUSIONS: The FEV1, exacerbations, oral corticosteroids, symptoms score allows clinicians to quantify response in severe uncontrolled asthma patients who are being treated with mAbs.

Launch and preliminary analysis of Hospital de La Princesa's inter-specialists biological therapies unit.

We herein describe an inter-specialists unit for the monitoring and management of biological therapies and analyze the utilization of biological agents across specialties and diseases. Protocols and therapeutic objectives, as well as outcomes and protocol deviations, are shared and discussed periodically between specialists. All patients treated at one centre with any biological treatment from January 2000 by rheumatology, gastroenterology, dermatology, or neurology, regardless diagnosis, are identified by Clinical Pharmacy and included in an ongoing database that detects use and outcome. The drugs, survival, and reasons for discontinuation differ significantly across specialties. This approach has helped us recognizing the challenges and size of the problem of sharing expensive medications across specialties, and has served as a starting point to contribute to the better use of these compounds.

Adherence to biologic therapies and associated factors in rheumatoid arthritis, spondyloarthritis and psoriatic arthritis: a systematic literature review.

OBJECTIVES: To analyse the evidence on adherence to biologic therapies in rheumatoid arthris (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). METHODS: Systematic review of studies retrieved by a sensitive search strategy in MEDLINE database (1961 through March 2012). To be selected, studies had to include patients with RA, SpA, or PsA, treatment with intravenous or subcutaneous biologic therapies, and had to report on measures of adherence. By design, only randomised controlled trials (RCT) or high quality cohort studies with a control group were selected. RESULTS: A total of 24 studies were included, of which 12 reported results from national or local biologic registers, 9 were retrospective studies, 2 prospective studies, and only one was an RCT. Patients included were mostly women with diagnosis of RA or SpA and, less frequently, PsA. There was a great variability in the definition of adherence, measurement methods, and associated factors analysed. In general, adherence to etanercept was superior to that of other biologics, by the measures utilised. The main predictive factors - age, sex, comorbidity, baseline clinical condition, previous or concomitant use of DMARDs, anti-TNF in monotherapy or in combination with MTX - produced diverse, even divergent results across studies. CONCLUSIONS: There is a wide variability related to the adherence concept and its measurement, reflecting the complexity of the phenomenon. In order to draw more consistent conclusions about the relative value of predictive factors on adherence and persistence of biological therapy, larger controlled studies with better selection of variables and analysis of interactions are needed.

Dietary supplements for chronic gout.

BACKGROUND: Dietary supplements are frequently used for the treatment of several medical conditions, both prescribed by physicians or self administered. However, evidence of benefit and safety of these supplements is usually limited or absent. OBJECTIVES: To assess the efficacy and safety of dietary supplementation for people with chronic gout. SEARCH METHODS: We performed a search in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL on 6 June 2013. We applied no date or language restrictions. In addition, we performed a handsearch of the abstracts from the 2010 to 2013 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) conferences, checked the references of all included studies and trial registries. SELECTION CRITERIA: We considered all published randomised controlled trials (RCTs) or quasi-RCTs that compared dietary supplements with no supplements, placebo, another supplement or pharmacological agents for adults with chronic gout for inclusion. Dietary supplements included, but were not limited to, amino acids, antioxidants, essential minerals, polyunsaturated fatty acids, prebiotic agents, probiotic agents and vitamins. The main outcomes were reduction in frequency of gouty attacks and trial participant withdrawal due to adverse events. We also considered pain reduction, health-related quality of life, serum uric acid (sUA) normalisation, function (i.e. activity limitation), tophus regression and the rate of serious adverse events. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We identified two RCTs (160 participants) that fulfilled our inclusion criteria. As these two trials evaluated different diet supplements (enriched skim milk powder (SMP) and vitamin C) with different outcomes (gout flare prevention for enriched SMP and sUA reduction for vitamin C), we reported the results separately.One trial including 120 participants, at moderate risk of bias, compared SMP enriched with glycomacropeptides (GMP) with unenriched SMP and with lactose over three months. Participants were predominantly men aged in their 50's who had severe gout. The frequency of acute gout attacks, measured as the number of flares per month, decreased in all three groups over the study period.The effects of enriched SMP (SMP/GMP/G600) compared with the combined control groups (SMP and lactose powder) at three months in terms of mean number of gout flares per month were uncertain (mean ± standard deviation (SD) flares per month: 0.49 ± 1.52 in SMP/GMP/G60 group versus 0.70 ± 1.28 in control groups; mean difference (MD) -0.21, 95% confidence interval (CI) -0.76 to 0.34; low-quality evidence). The number of withdrawals due to adverse effects was similar in both groups although again the results were imprecise (7/40 in SMP/GMP/G600 group versus 11/80 in control groups; risk ratio (RR) 1.27, 95% CI 0.53 to 3.03; low-quality evidence). The findings for adverse events were also uncertain (2/40 in SMP/GMP/G600 group versus 3/80 in control groups; RR 1.33, 95% CI 0.23 to 7.66; low-quality evidence). Gastrointestinal events were the most commonly reported adverse effects. Pain from self reported gout flares (measured on a 10-point Likert scale) improved slightly more in the SMP/GMP/G600 group compared with controls (mean ± SD reduction -1.97 ± 2.28 points in SMP/GMP/G600 group versus -0.94 ± 2.25 in control groups; MD -1.03, 95% CI -1.96 to -0.10; low-quality evidence). This was an absolute reduction of 10% (95% CI 20% to 1% reduction), which may not be of clinical relevance. Results were imprecise for the outcome improvement in physical function (mean ± SD Health Assessment Questionnaire (HAQ)-II (scale 0 to 3, 0 = no disability): 0.08 ± 0.23 in SMP/GMP/G60 group versus 0.11 ± 0.31 in control groups; MD -0.03, 95% CI -0.14 to 0.08; low-quality evidence). Similarly, results for sUA reduction were imprecise (mean ± SD reduction: -0.025 ± 0.067 mmol/L in SMP/GMP/G60 group versus -0.010 ± 0.069 in control groups; MD -0.01, 95% CI -0.04 to 0.01; low-quality evidence). The study did not report tophus regression and health-related quality of life impact.One trial including 40 participants, at moderate to high risk of bias, compared vitamin C alone with allopurinol and with allopurinol plus vitamin C in a three-arm trial. We only compared vitamin C with allopurinol in this review. Participants were predominantly middle-aged men, and their severity of gout was representative of gout in general. The effect of vitamin C on the rate of gout attacks was not assessed. Vitamin C did not lower sUA as much as allopurinol (-0.014 mmol/L in vitamin C group versus -0.118 mmol/L in allopurinol group; MD 0.10, 95% CI 0.06 to 0.15; low-quality evidence). The study did not assess tophus regression, pain reduction or disability or health-related quality of life impact. The study reported no adverse events and no participant withdrawal due to adverse events. AUTHORS' CONCLUSIONS: While dietary supplements may be widely used for gout, this review has shown a paucity of high-quality evidence assessing dietary supplementation.

Calcium supplementation and kidney stone risk in osteoporosis: a systematic literature review.

OBJECTIVES: This paper aims to examine the risk of nephrolithiasis in patients with osteoporosis and calcium supplementation. METHODS: This work is based on the systematic review of studies retrieved by a sensitive search strategy in Medline and Embase (1991-2010), and the Cochrane Central register of Controlled Trials (CENTRAL) up to 2010. The abstracts of the annual scientific meetings of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) (2008-2010) were also examined. The selection criteria were the following: patients with osteoporosis, on calcium supplementation alone or associated with other treatments for osteoporosis. We measured the likelihood of developing kidney stones, renal colic, changes in urinary sediment and serum parameters. We selected systematic literature reviews, randomised clinical trials (RCT) and cohort studies. RESULTS: We included 10 studies, 8 RCT and 2 cohort studies of moderate quality. All patients had osteoporosis (>8.000 patients), they were mostly women with a mean age of 50-70 years. Daily calcium doses varied from 120 mg up to 1.500 mg, and treatment duration from 3 days to 3 years. Changes in urinary sediment were found, but in general they were not clinically relevant. No cases of nephrolitiasis were found in more than a half of the included studies. In total there were 3 cases of kidney stone, 2 urinary tract calcifications, 16 cases of nephrolithiasis or urolithiasis, 4 of haematuria and 5 patients reporting kidney pain. CONCLUSIONS: According to our results, calcium supplements in the treatment of osteoporosis alone or in combination with another type of treatment does not significantly increase the risk of nephrolithiasis or renal colic.

Infecciones en pacientes tratados con antagonistas del factor de necrosis tumoral: incidencia, etiología y mortalidad en el registro BIOBADASER / Infections in patients treated with tumor necrosis factor antagonists: incidence, etiology and mortality in the BIOBADASER registry

Background and objectives: Whether the use of tumor necrosis factor antagonists increases the risk of infection remains a subject of open debate. Developing effective strategies of prevention and empirical treatment entails carefully establishing the etiology and prognosis of the infections.Patients and methods: Analysis of the Spanish registry BIOBADASER (Feb-2000 to Jan-2006), a national drug safety registry of patients with rheumatic diseases. Results: 907 episodes of infection occurring in 6,969 patients were analyzed. The infection incidence observed was 53.09 cases/1,000 patients-years (CI 95% 49.69-56.66). The most frequent infections were skin infection (12.18 cases/1,000 patients-yrs), pneumonia (5.97 cases/1,000 patients-yrs), cystitis (3.92 cases/1,000 patients-yrs), tuberculosis (3.51 cases/1,000 patients-yrs) and arthritis (3.76 cases/1,000 patients-yrs). Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa and Salmonella spp. emerged as important pathogens. Varicella zoster virus and Herpes simplex virus caused most cases of viral infections. Mucocutaneous candidiasis accounted for most fungal infections. Mortality was increased in infected patients (log-rank test p<0.0001). Pneumonia, sepsis, tuberculosis, abdominal infection and endocarditis were associated with significant attributable mortality.Conclusions: A significant number of bacterial, viral and fungal infections occurred in patients with rheumatic diseases treated with TNF antagonists. The information of this study can illuminate clinicians globally on how to address infection in this vulnerable group of patients (AU)

Fundamento y objetivo: El aumento del riesgo de infección en la utilización de los antagonistas del factor de necrosis tumoral (TNF) sigue siendo un tema de debate abierto. El desarrollo de estrategias eficaces de prevención y tratamiento empírico implica establecer la etiología y el pronóstico de las infecciones. Pacientes y métodos: Análisis del registro español BIOBADASER (febrero 2000 a enero 2006), un registro de terapias biológicas en pacientes con enfermedades reumáticas.Resultados: En los 6.969 pacientes registrados a la fecha del análisis, se produjeron 907 episodios de infección. La incidencia de infección observada fue de 53,09 casos/1.000 pacientes-año (IC 95% 49,69-56,66). Las infecciones más frecuentes fueron las de piel (12,18 casos/1.000 pacientes-año), neumonía (5,97 casos/1.000 pacientes-año), cistitis (3,92 casos/1.000 pacientes-año), tuberculosis (3,51 casos/1.000 pacientes-año) y articulares (3,76 casos/1.000 pacientes-año). Emergen como patógenos importantes Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa y Salmonella spp. El virus de la varicela zóster y el virus del herpes simple causaron la mayoría de los casos de infecciones virales con germen identificable. La candidiasis mucocutánea fue la más frecuente entre las infecciones fúngicas. La mortalidad fue mayor en los pacientes infectados (p-log-rank<0,0001). La aparición de una neumonía, sepsis, tuberculosis, infección abdominal y endocarditis se asociaron significativamente con la mortalidad. Conclusiones: Un número significativo de infecciones bacterianas, víricas y fúngicas se produjeron en pacientes con enfermedades reumáticas tratadas con antagonistas del TNF. La información de este estudio puede suponer un avance para la medicina sobre cómo tratar la infección en este grupo vulnerable de pacientes (AU)

Consenso SER sobre la gestión de riesgo del tratamiento con terapias biológicas en pacientes con enfermedades reumáticas / Consensus statement of the spanish society of rheumatology on risk management of biologic therapy in rheumatic patients

Objetivo: Dado el creciente uso de las terapias biológicas en distintas enfermedades reumatológicas, y la importancia de la gestión de riesgo de las mismas, desde la Sociedad Española de Reumatología (SER) se ha impulsado el desarrollo de recomendaciones basadas en la mejor evidencia posible. Estas deben de servir de referencia para reumatólogos e implicados en el tratamiento de pacientes en tratamiento o en los que se quiere indicar la terapia biológica independientemente de su enfermedad de base. Métodos: Las recomendaciones se emitieron siguiendo la metodología de grupos nominales. El nivel de evidencia y el grado de recomendación se clasificaron según el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por técnica Delphi. Se utilizó toda la información de consensos y guías de práctica clínica previas. Resultados: Se realizan recomendaciones sobre la gestión del riesgo del uso de las terapias biológicas en pacientes con enfermedades reumática. Incluyen la gestión del riesgo de la indicación, gestión del riesgo antes de iniciar el tratamiento, gestión del riesgo durante el seguimiento, actitud ante acontecimientos adversos, y actitud en situaciones especiales. Conclusiones: Se presentan las recomendaciones SER sobre la gestión del riesgo del tratamiento con terapias biológicas (AU)

Objective: Due to the increasing use of biologic therapy in rheumatic diseases and the importance of its risk management, the Spanish Society of Rheumatology (SER) has promoted the development of recommendations based on the best evidence available. These recommendations should be a reference to rheumatologists and those involved in the treatment of patients who are using, or about to use biologic therapy irrespectively of the rheumatic disease. Methods: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. Evidence from previous consensus and clinical guidelines was used. Results: We have produced recommendations on risk management of biologic therapy in rheumatic patients. These recommendations include indication risk management, risk management before the use of biologic therapy, risk management during follow-up, attitude to adverse events, and attitude to special situations. Conclusions: We present the SER recommendations related to biologic therapy risk management (AU)

[Consensus statement of the Spanish Society of Rheumatology on risk management of biologic therapy in rheumatic patients]. / Consenso SER sobre la gestión de riesgo del tratamiento con terapias biológicas en pacientes con enfermedades reumáticas.

OBJECTIVE: Due to the increasing use of biologic therapy in rheumatic diseases and the importance of its risk management, the Spanish Society of Rheumatology (SER) has promoted the development of recommendations based on the best evidence available. These recommendations should be a reference to rheumatologists and those involved in the treatment of patients who are using, or about to use biologic therapy irrespectively of the rheumatic disease. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. Evidence from previous consensus and clinical guidelines was used. RESULTS: We have produced recommendations on risk management of biologic therapy in rheumatic patients. These recommendations include indication risk management, risk management before the use of biologic therapy, risk management during follow-up, attitude to adverse events, and attitude to special situations. CONCLUSIONS: We present the SER recommendations related to biologic therapy risk management.

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

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

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

Terapias anti-TNF y neoplasias / Anti-TNF therapy and cancer

El factor de necrosis tumoral (TNF) está implicado en el control del crecimiento de tumores además de en la respuesta inflamatoria sistémica. El bloqueo del TNF produce un recelo comprensible en pacientes con riesgo de cáncer. Ni en el desarrollo preclínico ni durante los ensayos clínicos de los anti-TNF se detectaron alarmas claras. Los registros de seguridad de biológicos establecidos en el período poscomercialización han concluido que el cáncer en general no está aumentado con respecto de lo esperado en una población de AR con el uso prolongado de anti-TNF. Un meta-análisis de ensayos clínicos de infliximab y adalimumab mostró un aumento de hasta tres veces el riesgo de cáncer, pero al corregir la exposición por el tiempo en los mismos no se encontró. En BIOBADASER tenemos evidencias que apoyan la seguridad a largo plazo. A largo plazo, y si realmente la actividad inflamatoria de la enfermedad subyacente está controlada, el riesgo de desarrollar un cáncer es igual que el de cualquier paciente (AU)

Tumor necrosis factor (TNF) is implicated in the control of tumoral growth in addition to the systemic inflammatory response. TNF blockage produces a compressible reservation in patients with risk factors for cancer. No clear evidence for this came out from pre-clinical or clinical trials. Biosafety registries established in the post-marketing phase have concluded that, in general, cancer cases have not increased over what is expected in a population with RA exposed to the prolongued use of anti-TNF drugs. A meta-analysis of clinical trials which used infliximab and adalimumab for RA treatment showed an increase of up to three times the risk of developing cancer, but this disappeared after correcting for time. Biobadaser shows evidence that support long-term safety. In the long-term, and if the inflammatory disease activity is truly under control, the risk of developing cancer is the same as with any other patient (AU)

Actualización de BIOBADASER / Update of BIOBADASER

Hasta el 1 de septiembre de 2008 se han registrado 9.352 pacientes procedentes de 100 centros que han aportado información sobre 12.136 tratamientos biológicos. El tratamiento se suspendió en 4.281 (35%) ocasiones: en igual proporción como resultado de un acontecimiento adverso (1.782 [42%]) que de ineficacia o pérdida de eficacia (1.816 [42%]). Se han comunicado 6.814 acontecimientos adversos, de los cuales el más frecuente es la infección (2.656 [39%]), seguido de las alteraciones relacionadas con la administración (1.009 [15%]) y de los trastornos de la piel y del tejido subcutáneo (521 [8%]) (AU)

As of September 1st, 2008 BIOBADASER has included 9352 patients from 100 centers that provide information on 12,136 treatments with biological therapies. Treatment was discontinued in 4281 (35%) occasions, in the same proportion as a result of an adverse event [1,782 (42%)] and inefficiency or loss of effectiveness [1,816 (42%)]. There have been reported 6814 adverse events, of which the most frequent are infections [2,656 (39%)], followed by disorders related to the administration [1,009 (15%)] and disorders of the skin and subcutaneous tissue [521 (8%)] (AU)

Cambios entre anti-TNF, ¿están siempre justificados? / No disponible

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Reacciones adversas relacionadas con la administración de inhibidores del TNF. Análisis de un registro de terapias biológicas / Adverse reactions related to the administration of TNF inhibitors. Analysis of a registry of biologic therapy

Objetivo: Estimar la frecuencia de aparición de las reacciones relacionadas con la administración (RRA), los síntomas asociados a las graves o tardías, la ventana de exposición desde inicio de la terapia biológica y si hay diferencias entre infliximab, etanercept y adalimumab. Pacientes y método: BIOBADASER es un registro de acontecimientos adversos establecido en 2001 para determinar la seguridad de las terapias biológicas en enfermedades reumáticas. Contiene datos de los pacientes, tratamiento y acontecimientos adversos relevantes. Resultados: Se registró un total de 496 RRA relevantes en 442 pacientes, lo que representa un 19,6% (496/2.531) de todos los acontecimientos adversos comunicados y un 6,3% de los pacientes registrados (442/6.969). La tasa de incidencia de RRA por 1.000 años-paciente con infliximab es de 28 casos (intervalo de confianza [IC] del 95%, 25-31), con etanercept 0,2 (IC del 95%, 0,1-0,4) y con adalimumab 0,2 (IC del 95%, 0,07-0,7). En más de la mitad de las RRA, el acontecimiento adverso da lugar a la interrupción del fármaco relacionado y en el 5% de los casos el paciente requiere ser hospitalizado. Más del 20% de las RRA ocurren después de 15 meses de tratamiento, incluso aparecen después de 5 años. En las reacciones adversas tardías los síntomas comunicados con más frecuencia son erupciones, fiebre, malestar general y mialgias. Conclusiones: Las RRA pueden aparecer en cualquier momento de la enfermedad, son una de las causas más frecuentes de interrupción de tratamiento con infliximab. Aunque con menor frecuencia, también se relacionan con etanercept y adalimumab en síntomas que pueden no identificarse como tales (AU)

Objective: To estimate the frequency of administration related reactions (ARR), the risk window from the starting date, and finally if there are any differences between infliximab, etanercept and adalimumab. Patients and method: BIOBADASER is an adverse events registry established in 2001 for active long-term follow-up of safety of biological therapies in rheumatic patients. Data from patients, diagnosis, treatment, and adverse events are recorded. Results: Four-hundred ninety six relevant ARR were registered, 19.6% (496/2531) of all the adverse events communicated and 6.3% (496/2531) of all the patients registered. The incidence rate per 1000 patients-year with infliximab is 28 cases (95% CI, 25-31), with etanercept 0.2 (95% CI, 0.1-0.4) and with adalimumab 0.2 (95% CI, 0.07-0.7). Treatment was interrupted in more than 50% of all the ARR and 5% of all patients were hospitalized. More than 20% ARR happened after 15 months of treatment; in addition 2 appeared after 5 years of treatment. In delayed reactions the symptoms that most frequently were recorded were rash, fever, malaise, and myalgia. Conclusions: ARR can appear in any moment of the treatment; they are among the most frequent causes of treatment interruption. Although with less frequency, ARR are also associated with etanercept and adalimumab with symptoms that cannot be identified as such (AU)

Revisión sistemática: ozonoterapia en enfermedades reumáticas / Ozone therapy in rheumatic diseases: a systematic review

Objetivo: Analizar, mediante una revisión sistemática, la eficacia sobre la que se basa el uso de la ozonoterapia en las enfermedades osteomusculares. Métodos: Se realizó una búsqueda en PubMed, Embase y Cochrane Library utilizando descriptores muy sensibles para poder captar todos los estudios de ozonoterapia. Se seleccionaron todos los estudios en los que se mostrara la eficacia o efectividad de la ozonoterapia en cualquier enfermedad osteomuscular. Resultados: Sólo se identificaron 6 estudios relacionados, 5 en hernia discal y 1 en síndrome Raynaud. De los 5 estudios en hernia discal, sólo 3 eran ensayos clínicos, y en ninguno la asignación al grupo de estudio era aleatoria. Los participantes de los estudios eran en general pacientes con hernia discal sintomática no muy grande. Existe una gran variabilidad en las dosis de ozono inyectadas, así como en los controles frente a los que se comparan. Las medidas de desenlace son todas subjetivas y no existe evaluación ciega de los resultados. El estudio de síndrome de Raynaud incluía sólo a 4 pacientes. No se valoran efectos adversos en detalle. Conclusiones: El uso de la ozonoterapia en las enfermedades osteomusculares se basa en estudios de baja calidad. No hay en el momento actual un argumento sugerente de una adecuada relación riesgo/beneficio de la ozonoterapia en las enfermedades reumáticas(AU)

Objective: To perform a systematic review to analyze the efficacy on which the use of ozone therapy in musculoskeletal diseases is based. Methods: A literature search was performed in PubMed, Embase and the Cochrane Library using highly sensitive search terms to identify all studies on ozone therapy. All studies showing the efficacy or effectiveness of ozone therapy in any musculoskeletal disease were selected. Results: Only 6 relevant studies were identified, 5 in lumbar disk herniation and 1 in Raynaud’s syndrome. Of the 5 studies in disk herniation, only 3 were clinical trials and none used random allocation. Study participants were generally patients with symptomatic small discal hernias. There was wide variability in the dose of ozone injected as well as in the controls used for comparison. All outcome measures were subjective and there was no blinded evaluation of the results. The study in Raynaud’s syndrome included only 4 patients. Adverse effects were not evaluated in detail. Conclusions: The use of ozone therapy in musculoskeletal diseases is based on poor quality studies. Currently, data supporting an adequate risk/benefit ratio for ozone therapy in rheumatic diseases is lacking(AU)

[Ozone therapy in rheumatic diseases: a systematic review]. / Revisión sistemática: ozonoterapia en enfermedades reumáticas.

OBJECTIVE: To perform a systematic review to analyze the efficacy on which the use of ozone therapy in musculoskeletal diseases is based. METHODS: A literature search was performed in PubMed, Embase and the Cochrane Library using highly sensitive search terms to identify all studies on ozone therapy. All studies showing the efficacy or effectiveness of ozone therapy in any musculoskeletal disease were selected. RESULTS: Only 6 relevant studies were identified, 5 in lumbar disk herniation and 1 in Raynaud's syndrome. Of the 5 studies in disk herniation, only 3 were clinical trials and none used random allocation. Study participants were generally patients with symptomatic small discal hernias. There was wide variability in the dose of ozone injected as well as in the controls used for comparison. All outcome measures were subjective and there was no blinded evaluation of the results. The study in Raynaud's syndrome included only 4 patients. Adverse effects were not evaluated in detail. CONCLUSIONS: The use of ozone therapy in musculoskeletal diseases is based on poor quality studies. Currently, data supporting an adequate risk/benefit ratio for ozone therapy in rheumatic diseases is lacking.