OBJECTIVES: To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA.
METHODS: PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.
RESULTS: Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias.
CONCLUSIONS: This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.
Osteoarthritis is the most common joint disorder worldwide. The predominant symptom, pain, is usually treated with acetaminophen or oral non-steroidal anti-inflammatory drugs, although they are associated with a significant risk of side effects. Topical capsaicin may represent an effective and safe alternative. The aim of this review is to examine the evidence for the efficacy and safety profile of topical capsaicin in the management of pain caused by osteoarthritis. Databases were searched for articles published between 2004 and 2016, in Portuguese, English or Spanish, using the search terms "capsaicin" and "osteoarthritis". When compared to placebo, it was found that topical capsaicin has a good safety profile and efficacy in reducing osteoarthritis pain of the hand, knee, hip or shoulder. However, the studies have significant limitations, the most important the difficulty of blinding. It is attributed to this review the strength of recommendation B.
La artrosis es la enfermedad articular crónica que presenta mayor prevalencia, en la cual el dolor es uno de los principales síntomas y el mayor determinante de la pérdida de funcionalidad. Se han planteado múltiples opciones terapéuticas, entre ellas la glucosamina, pero su real utilidad aún no ha sido claramente establecida. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos, identificamos 11 revisiones sistemáticas que en conjunto incluyen 35 estudios aleatorizados que responden la pregunta de este resumen. Extrajimos la información relevante, realizamos un metanálisis y preparamos tablas de resumen de los resultados utilizando el método GRADE. Concluimos que no está claro que la glucosamina disminuya el dolor o mejore la funcionalidad en la artrosis porque la certeza de la evidencia es muy baja.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
BACKGROUND: Traditional Chinese medicine (TCM) has been accepted as a complementary therapy for knee osteoarthritis. However, the efficacy and safety of the intervention were still conflicting and uncertain. Meanwhile, the quality of methodology and evidence in the field was unknown.
OBJECTIVE: To summarize the characteristics and critically evaluate the quality of methodology, as well as the evidence of systematic reviews (SRs) on TCM for knee osteoarthritis.
METHODS: Five electronic databases were searched from inception to April 2016. The methodological quality of the included studies was assessed by AMSTAR and ROBIS. The quality of the evidence was determined using the GRADE approach.
RESULTS: Ten SRs were included. The conclusions suggest that TCM provides potential benefits for patients with knee osteoarthritis. These benefits include pain relief, functional improvement, and presence of few adverse events. Limitations of the methodological quality mainly included the lack of a-priori protocol or protocol registration and incomprehensive literature search. A list of excluded studies was also not provided. The overall quality of evidence in the SRs was poor, ranging from "very low" to "low," mainly because of the serious risk of bias of original trials, inconsistencies, and imprecision in the outcomes.
CONCLUSIONS: TCM generally appears to be effective for knee osteoarthritis treatment. However, the evidence is not robust enough because of the methodological flaws in SRs. Hence, these conclusions on available SRs should be treated with caution for clinical practice.
La artrosis es la enfermedad articular crónica que presenta mayor prevalencia, en la cual el dolor es uno de los principales síntomas y el mayor determinante de la pérdida de funcionalidad. Se han planteado múltiples opciones terapéuticas, entre ellas el condroitín sulfato, pero su real utilidad aún no ha sido claramente demostrada. Para aclarar esta interrogante utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples fuentes de información. Identificamos 13 revisiones sistemáticas que en conjunto incluyen 50 estudios aleatorizados que responden la pregunta de este resumen. Extrajimos la información relevante, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Concluimos que no está claro si el uso de condroitín sulfato produce una mejoría en el dolor o la funcionalidad en la artrosis porque la certeza de la evidencia es muy baja.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
Fundamento: Las terapias de medicina complementaria y alternativa (CAM) pueden ser utilizadas como un enfoque no farmacológico para el manejo del dolor crónico. Mientras cientos de ensayos sobre la modalidad CAM individual se han llevado a cabo, una visión global de sus resultados es actualmente insuficiente para los médicos e investigadores del dolor. Esta revisión general sintetizó la calidad de la evidencia meta-analítica que apoya la eficacia, tolerabilidad y seguridad de las terapias de CAM para el manejo del dolor crónico. MATERIALES Y MÉTODOS: MEDLINE, EMBASE, CINAHL y CENTRAL fueron examinados entre octubre de 1991 y noviembre de 2016. Se evaluaron los ensayos clínicos (aleatorizados y no aleatorios) con metanálisis que investigaban la utilidad de cualquier modalidad de CAM para el dolor crónico. El alivio del dolor después de la intervención fue el principal resultado y los resultados secundarios incluyeron la adherencia de los pacientes y la incidencia de efectos adversos durante el protocolo CAM. RESULTADOS: Se incluyeron 26 revisiones (207 ensayos clínicos,> 12.000 participantes), alrededor de 18 modalidades de CAM, incluidas en productos naturales, prácticas mentales y corporales u otros enfoques de salud complementarios. Se encontró que el cannabis inhalado, las imágenes motoras graduadas y la inyección de Kushen compuesto (una forma de medicina china) eran los más eficaces (con tamaños de efecto moderado a alto y baja heterogeneidad) y tolerables (≥80% de adherencia a los protocolos del estudio) alivio del dolor. Cuando se informó, los efectos adversos relacionados con estas CAM fueron menores. Conclusión: Aunque varios CAM se encontraron eficaces para el alivio del dolor crónico, todavía no está claro cuando estas modalidades son una opción razonable contra o en conjunción con los tratamientos de corriente. En ese sentido, se necesita investigación futura con un claro énfasis en la evaluación concurrente de la eficacia global de la CAM y la adherencia / tolerancia del paciente.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
Osteoarthritis refers to a clinical syndrome of joint pain accompanied by varying degrees of functional limitation and reduced quality of life. It is the most common form of arthritis, and one of the leading causes of pain and disability worldwide. The most commonly affected peripheral joints are the knees, hips and small hand joints. Although pain, reduced function and effects on a person’s ability to carry out their day-to-day activities can be important consequences of osteoarthritis, pain in itself is of course a complex biopsychosocial issue, related in part to person expectations and self-efficacy, and associated with changes in mood, sleep and coping abilities. There is often a poor link between changes on an X-ray and symptoms: minimal changes can be associated with a lot of pain and modest structural changes to joints oftencan occur without with minimal accompanying symptoms. Contrary to popular belief, osteoarthritis is not caused by ageing and does not necessarily deteriorate. There are a number of management and treatment options (both pharmacological and non-pharmacological), which this guideline addresses and which offer effective interventions for control of symptoms and improving function. Osteoarthritis is characterised pathologically by localised loss of cartilage, remodelling of adjacent bone and associated inflammation. A variety of traumas may trigger the need for a joint to repair itself. Osteoarthritis includes a slow but efficient repair process that often compensates for the initial trauma, resulting in a structurally altered but symptom-free joint. In some people, because of either overwhelming trauma or compromised repair, the process cannot compensate, resulting in eventual presentation with symptomatic osteoarthritis; this might be thought of as ‘joint failure’. This in part explains the extreme variability in clinical presentation and outcome that can be observed between people, and also at different joints in the same person. There are limitations to the published evidence on treating osteoarthritis. Most studies have focused on knee osteoarthritis, and are often of short duration using single therapies. Although most trials have looked at single joint involvement, in reality many people have pain in more than one joint, which may alter the effectiveness of interventions. This guideline update was originally intended to include recommendations based on a review of new evidence about the use of paracetamol, etoricoxib and fixed-dose combinations of NSAIDs plus gastroprotective agents in the management of osteoarthritis. Draft recommendations based on the evidence reviews for these areas were presented in the consultation version of the guideline. Stakeholder feedback at consultation indicated that the draft recommendations, particularly in relation to paracetamol, would be of limited clinical application without a full review of evidence on the pharmacological management of osteoarthritis. NICE was also aware of an ongoing review by the MHRA of the safety of over-the-counter analgesics. Therefore NICE intends to commission a full review of evidence on the pharmacological management of osteoarthritis, which will start once the MHRA’s review is completed, to inform a further guideline update. Until that update is published, the original recommendations (from 2008) on the pharmacological management of osteoarthritis remain current advice. However, the GDG would like to draw attention to the findings of the evidence review on the effectiveness of paracetamol that was presented in the consultation version of the guideline. That review identified reduced effectiveness of paracetamol in the management of osteoarthritis compared with what was previously thought. The GDG believes that this information should be taken into account in routine prescribing practice until the intended full review of evidence on the pharmacological management of osteoarthritis is published (see the NICE website for further details).
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
Esta revisión evalúa críticamente la literatura sobre la medicina complementaria y alternativa (CAM) como opciones de tratamiento para la artritis reumatoide y la osteoartritis. Diseño: Se realizaron búsquedas en bases de datos electrónicas para identificar todas las revisiones pertinentes sistemáticas de la efectividad de la CAM en la artritis reumatoide y la artrosis publicados entre enero de 2010 y enero de 2011. Las críticas fueron definidas como sistemática si incluyeran inclusión explícita y repetible y criterios de exclusión para los estudios. La calidad metodológica se evaluó mediante los criterios de Oxman para las revisiones sistemáticas. Resultados: Cinco revisiones sistemáticas cumplieron los criterios de inclusión. Todos llegaron a conclusiones prudentes. Cuatro opiniones eran de alta calidad y una fue cargado con alto riesgo de sesgo. La evidencia que apoya la eficacia de la CAM como una opción de tratamiento para la artritis reumatoide y la osteoartritis es ambiguo.
To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA.
METHODS:
PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.
RESULTS:
Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias.
CONCLUSIONS:
This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.
