Balneoterapia (o terapia de spa) para la artritis reumatoide
Resumen
Antecedentes
Actualmente no se conoce ninguna cura para la artritis reumatoide (AR), por lo que el tratamiento suele centrarse en el control de síntomas como el dolor, la rigidez y la movilidad. Las opciones de tratamiento incluyen intervenciones farmacológicas, tratamientos de fisioterapia y balneoterapia. La balneoterapia se define como el baño en aguas minerales o termales naturales (por ejemplo, baños minerales, baños de azufre, baños del Mar Muerto), utilizando fangos o haciendo ambas cosas. A pesar de su popularidad, la evidencia científica informada sobre la efectividad o la eficacia de la balneoterapia es escasa. Esta revisión, que evalúa los efectos de la balneoterapia en pacientes con AR, es una actualización de una revisión Cochrane publicada por primera vez en 2003 y actualizada en 2008.
Objetivos
Realizar una revisión sistemática de los beneficios y daños de la balneoterapia en pacientes con AR en cuanto al dolor, la mejoría, la discapacidad, las articulaciones sensibles, las articulaciones inflamadas y los eventos adversos.
Métodos de búsqueda
Se realizaron búsquedas en el Cochrane 'Rehabilitation and Related Therapies' Field Register (hasta diciembre de 2014), el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (2014, número 1), MEDLIINE (1950 hasta diciembre de 2014), EMBASE (1988 hasta diciembre de 2014), el Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 hasta diciembre de 2014), la Allied and Complementary Medicine Database (AMED) (1985 hasta diciembre de 2014), PsycINFO (1806 hasta diciembre de 2014) y la Physiotherapy Evidence Database (PEDro). No se aplicaron restricciones de idioma; sin embargo, los estudios que no se informaron en inglés, neerlandés, danés, sueco, noruego, alemán o francés están a la espera de evaluación. También se realizaron búsquedas en la World Health Organization (WHO) International Clinical Trials Registry Platform para encontrar ensayos en curso y recientemente finalizados.
Criterios de selección
Los estudios eran elegibles si se trataba de ensayos controlados aleatorizados (ECA) consistentes en participantes con AR definitiva o clásica según se define en los criterios de la American Rheumatism Association (ARA) de 1958, los criterios de la ARA/American College of Rheumatology (ACR) de 1988 o los criterios de la ACR/European League Against Rheumatism (EULAR) de 2010, o por estudios que utilicen los criterios de Steinbrocker.
La intervención del estudio debía ser la balneoterapia y debía compararse con otra intervención o con ninguna intervención.
La World Health Organization (WHO) y la International League Against Rheumatism (ILAR) determinaron en 1992 un conjunto básico de ocho criterios de valoración en los ensayos clínicos relativos a los pacientes con AR. Se consideró el dolor, la mejoría, la discapacidad, las articulaciones sensibles, las articulaciones inflamadas y los eventos adversos entre las principales medidas de resultado. Se excluyeron los estudios en los que sólo se informaban las variables de laboratorio como medidas de resultado.
Obtención y análisis de los datos
Dos autores de la revisión seleccionaron los ensayos de forma independiente, realizaron la extracción de datos y evaluaron el riesgo de sesgo. Se resolvieron los desacuerdos por consenso y, si fue necesario, por adjudicación a terceros.
Resultados principales
Esta revisión incluye dos nuevos estudios y un total de nueve estudios con 579 participantes. Desafortunadamente, la mayoría de los estudios mostraron un riesgo poco claro de sesgo en la mayoría de los dominios. Cuatro de los nueve estudios no contribuyeron al análisis, ya que no presentaron datos.
Un estudio con 45 participantes con AR de la mano comparó los fangos versus placebo. No se encontraron diferencias estadísticamente significativas en cuanto al dolor en una escala analógica visual (EAV) de cero a 100 mm (diferencia de medias (DM) 0,50; intervalo de confianza (IC) del 95%: ‐0,84 a 1,84), la mejoría (riesgos relativos (RR) 0,96; IC del 95%: 0,54 a 1,70) o el número de articulaciones inflamadas en una escala de 0 a 28 (DM 0,60; IC del 95%: ‐0,90 a 2,10) (nivel de evidencia muy bajo). Se encontró un nivel muy bajo de evidencia de reducción del número de articulaciones sensibles en una escala de 0 a 28 (DM ‐4,60; IC del 95%: ‐8,72 a ‐0,48; 16% de diferencia absoluta). No se informó de ninguna discapacidad física ni se presentaron datos sobre retiros debidos a eventos adversos o sobre eventos adversos graves.
Dos estudios con 194 participantes con RA evaluaron la efectividad del radón adicional en los baños de dióxido de carbono. No se encontraron diferencias estadísticamente significativas entre los grupos para todos los resultados a los tres meses de seguimiento (nivel de evidencia bajo a moderado). Se observó cierto beneficio del radón adicional a los seis meses en cuanto a la frecuencia del dolor (RR 0,6; IC del 95%: 0,4 a 0,9; reducción del 31%; mejora en uno o más puntos (categorías) en una escala de 4 puntos; nivel de evidencia moderado) y una reducción del 9,6% en la intensidad del dolor en una EAV de cero a 100 mm (DM 9,6 mm; IC del 95%: 1,6 a 17,6; nivel de evidencia moderado). También se observó algún beneficio en un estudio que incluía a 60 participantes en cuanto a la mejoría en una o más categorías basadas en una escala de cuatro puntos (RR 2,3; IC del 95%: 1,1 a 4,7; diferencia absoluta del 30%; bajo nivel de evidencia). Los autores del estudio no informaron sobre discapacidad física, articulaciones sensibles, articulaciones inflamadas, retiros por eventos adversos o eventos adversos graves.
Un estudio con 148 participantes con AR comparó la balneoterapia (inmersión sentada) versus la hidroterapia (ejercicios en el agua), los ejercicios en tierra o la terapia de relajación. No se encontraron diferencias estadísticamente significativas en cuanto al dolor en el cuestionario McGill o en cuanto a la discapacidad física (nivel de evidencia muy bajo) entre la balneoterapia y las otras intervenciones. No se presentaron datos sobre la mejora, las articulaciones sensibles, las articulaciones inflamadas, los retiros por eventos adversos o los eventos adversos graves.
Un estudio que incluía a 57 participantes con AR evaluó la efectividad de los baños minerales (balneoterapia) versus ciclosporina A. No se encontraron diferencias estadísticamente significativas en la intensidad del dolor en un EAV de cero a 100 mm (DM 9,64; IC del 95%: ‐1,66 a 20,94; bajo nivel de evidencia) a las ocho semanas (diferencia absoluta 10%). Se encontró algún beneficio de la balneoterapia en la mejoría general en una escala de cinco puntos a las ocho semanas del 54% (RR 2,35; IC del 95%: 1,44 a 3,83). No se encontraron diferencias estadísticamente significativas (bajo nivel de evidencia) en el número de articulaciones inflamadas, pero sí algún beneficio de la ciclosporina A en el número de articulaciones sensibles (DM 8,9; IC del 95%: 3,8 a 14; nivel de evidencia muy bajo). No se informó sobre la discapacidad física, los retiros debidos a eventos adversos y los eventos adversos graves.
Conclusiones de los autores
La evidencia general es insuficiente para demostrar que la balneoterapia es más efectiva que la ausencia de tratamiento, que un tipo de baño es más efectivo que otro o que un tipo de baño es más efectivo que los fangos, el ejercicio o la terapia de relajación.
PICO
Resumen en términos sencillos
Balneoterapia (o terapia de spa) para la artritis reumatoide
Se revisó la evidencia sobre los beneficios y los daños de la balneoterapia (aguas minerales naturales, gases y fangos o terapia de balneario) en pacientes con artritis reumatoide. La balneoterapia se define como el baño en aguas minerales o termales naturales (por ejemplo, baños minerales, baños de azufre, baños del Mar Muerto), utilizando fangos o haciendo ambas cosas. Al buscar todos los estudios relevantes hasta diciembre de 2014, se encontraron nueve estudios con 579 pacientes. La calidad de la evidencia es muy baja, principalmente debido al escaso número de participantes en los estudios y a la preocupación por los diseños de los mismos.
Esta revisión muestra que en pacientes con artritis reumatoide:
‐ No se sabe con certeza si los fangos (balneoterapia) mejoran el dolor, el bienestar general y la inflamación de las articulaciones en comparación con el placebo (tratamiento falso) en los pacientes con AR de la mano. Los fangos pueden mejorar ligeramente la sensibilidad de las articulaciones en comparación con el placebo, pero en el estudio no se informó sobre la capacidad física y los eventos adversos.
‐ La adición de radón a los baños de dióxido de carbono no mejoró la intensidad del dolor a los tres meses, pero puede mejorar el bienestar general y el dolor a los seis meses en comparación con los baños de dióxido de carbono sin radón, pero esto puede haber sucedido por casualidad. En los estudios no se informó sobre la discapacidad física, las articulaciones sensibles e inflamadas y los eventos adversos.
‐ no se sabe con certeza si la balneoterapia (inmersión sentada) mejora el dolor y la función física en comparación con la hidroterapia, el ejercicio o la relajación. En el estudio no se informó de mejoras, articulaciones sensibles, articulaciones inflamadas y eventos adversos.
‐ no se sabe si los baños minerales (balneoterapia) mejoran el dolor y la inflamación de las articulaciones en comparación con el uso de un fármaco (Ciclosporina A). Los baños minerales pueden mejorar el bienestar general en comparación con la Ciclosporina A, y la Ciclosporina A puede mejorar el número de articulaciones sensibles en comparación con los baños minerales. No se informó la discapacidad física ni los eventos adversos.
‐ no se tiene información precisa sobre los efectos secundarios y las complicaciones de la balneoterapia. Esto es particularmente cierto para los efectos secundarios raros. Los efectos secundarios pueden incluir erupción cutánea, infección y accidentes, por ejemplo, resbalones en superficies húmedas cerca del área de baño. El único estudio que informó sobre los efectos secundarios declaró que no encontró ninguno.
¿Qué es la artritis reumatoide y qué es la balneoterapia?
Cuando se padece artritis reumatoide (AR), el sistema inmunológico, que normalmente combate las infecciones, inflama el revestimiento de las articulaciones, haciéndolas dolorosas, rígidas e inflamadas. En general, primero afecta las articulaciones pequeñas de las manos y los pies. Actualmente, no se conoce ninguna cura para la AR, así que los tratamientos tienen como objetivo aliviar el dolor y la rigidez y así mejorar la capacidad de movimiento.
La balneoterapia (baño en agua) es un tipo de terapia que tiene como objetivo reducir el dolor y mejorar el funcionamiento diario. La balneoterapia suele tener lugar en centros con baños termales o de agua de mar.
Authors' conclusions
Summary of findings
| Balneotherapy compared with placebo for participants with rheumatoid arthritis | ||||||
| Patient or population: participants with rheumatoid arthritis | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Placebo | Balneotherapy | |||||
| Pain intensity | Mean pain intensity in control groups was | Mean pain intensity in intervention groups was | 45 | ⊕⊝⊝⊝ | MD 0.50 (95% CI ‐0.84 to 1.84) Absolute difference 0.5% (95% CI ‐0.84% to 1.84%) Relative percent change 1% (95% CI ‐2% to 4%) No statistically significant or clinically relevant difference | |
| Improvement measures (> 30% reduction in number of swollen joints, > 30% reduction in number of tender joints, > 20% improvement in patient VAS for severity of pain and > 20% improvement in physician VAS) | 522 per 1000 | 501 per 1000 | RR 0.96 | 45 | ⊕⊝⊝⊝ | Absolute difference ‐2% (95% CI ‐31% to 27%) Relative percent change 5% (95% CI ‐42% to 70%) No statistically significant or clinically relevant difference |
| Physical disability Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Tender joints Number of painful joints Scale from 0 to 28 Follow‐up: 3 months | Mean number of tender joints in control groups was | Mean number of tender joints in intervention groups was | 45 | ⊕⊝⊝⊝ | MD ‐4.60 (95% CI ‐8.72 to ‐0.48) Absolute difference ‐16% (95% CI ‐31% to 2%) Relative percent change ‐37% (95% CI ‐70% to ‐4%) NNTB 32 (95% CI 10 to 717) | |
| Swollen joints Number of swollen joints Scale from 0 to 28 Follow‐up: 3 months | Mean number of swollen joints in control groups was | Mean number of tender joints in intervention groups was | 45 | ⊕⊝⊝⊝ | MD 0.60 (95% CI ‐0.90 to 2.10) Absolute difference 2% (95% CI ‐3% to 8%) Relative percent change 32% (95% CI ‐47% to 110%) No statistically significant or clinically relevant difference | |
| Withdrawal due to serious adverse events Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Adverse events Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| *The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aDowngraded because of imprecision. | ||||||
| Additional radon in carbon dioxide baths compared with carbon dioxide baths only for participants with rheumatoid arthritis | ||||||
| Patient or population: participants with rheumatoid arthritis | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Carbon dioxide baths only | Additional radon in carbon dioxide baths | |||||
| Pain intensity | Mean change in pain intensity in control groups was | Mean change in pain intensity in intervention groups was | 194 | ⊕⊕⊕⊝ | MD ‐4.49 (95% CI ‐13.41 to 4.44) Absolute difference 4.5% (95% CI ‐13.4 to 4.4) No statistically significant or clinically relevant difference | |
| Pain intensity | Mean change in pain intensity in control groups was | Mean change in pain intensity in intervention groups was | 194 | ⊕⊕⊕⊝ | MD ‐9.59 (95% CI ‐17.57 to ‐1.6) Absolute difference 9.5% (95% CI ‐17.5 to ‐1.6) Statistically significant but not clinically relevant difference | |
| Improvement | 267 per 1000 | 367 per 1000 | RR 1.38 (0.64 to 2.93) | 60 | ⊕⊕⊝⊝ | Absolute difference 10% (95% CI ‐13% to 33%) Relative percent change 38% (95% CI ‐36% to 22%) No statistically significant or clinically relevant difference |
| Improvement | 233 per 1000 | 533 per 1000 | RR 2.29 (1.1 to 4.74) | 60 (1 study) | ⊕⊕⊝⊝ | Absolute difference 30% (95% CI 10% to 60%) Relative percent change 129% (95% CI 10% to 474%) Statistically significant and clinical relevant difference |
| Physical disability Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Tender joints Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Swollen joints Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Withdrawal due to serious adverse events Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Adverse events Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| *The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aDowngraded because of imprecision. | ||||||
| Balneotherapy compared with drug treatment for participants with rheumatoid arthritis | ||||||
| Patient or population: participants with rheumatoid arthritis | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Drug treatment ‐ Cyclosporin A | Balneotherapy | |||||
| Pain intensity | Mean pain intensity in control groups was | Mean pain intensity in intervention groups was | 57 | ⊕⊝⊝⊝ | MD 9.64 (95% CI ‐1.66 to 20.94) Absolute difference 10% (95% CI ‐2% to 21%) Relative percent change 53% (95% CI ‐9% to 116%) No statistically significant or clinically relevant difference | |
| Improvement | 400 per 1000 | 940 per 1000 | RR 2.35 (1.44 to 3.83) | 57 | ⊕⊝⊝⊝ | Absolute difference 54% (95% CI 33% to 75%) Relative percent change 135% (95% CI 44% to 283%) NNTB 2 (95% CI 2 to 3) |
| Physical disability Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Tender joints Number of tender joints Scale from 0 to 28 Follow‐up: 8 weeks | Mean number of tender joints in control groups was | Mean number of tender joints in intervention groups was | 57 (1 study) | ⊕⊝⊝⊝ | MD 8.90 (95% CI 3.83 to 13.97) Absolute difference 31% (95% CI 17% to 50%) Relative percent change 228% (95% CI 98% to 358%) NNTB 22 (95% CI 8 to 96) | |
| Swollen joints Number of swollen joints Scale from 0 to 28 Follow‐up: 8 weeks | Mean number of swollen joints in control groups was | Mean number of tender joints in intervention groups was | 57 (1 study) | ⊕⊝⊝⊝ | MD 1.50 (95% CI ‐1.25 to 4.25) Absolute difference 5% (95% CI ‐4% to 15%) Relative percent change 79% (95% CI ‐66% to 224%) No statistically significant or clinical relevant difference | |
| Withdrawal due to serious adverse events Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Adverse events Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| *The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aDowngraded because of single study. | ||||||
Background
Description of the condition
Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation of the peripheral joints. In adults, the incidence of new cases is 50/100 000/y and one‐year prevalence is between 500 and 600/100 000 (0.5% to 1.0%) (Symmons 1994). Common symptoms of RA consist of a combination of pain, fatigue, stiffness, reduced range of motion in the joints and muscle weakness. Inflammation can cause progressive destruction of articular and periarticular structures (McInnes 2011; Symmons 2002). RA can affect all joints in the body. The natural course of the disease is a slow but inexorable deterioration in physical condition, leading to difficulty in activities of daily living and poor quality of life. Rheumatoid arthritis is a multi‐system disease that can affect internal organs, causing premature death. With adequate treatment targeted towards strongly reducing or abolishing inflammatory disease, many of these consequences can be prevented.
Description of the intervention
The term 'balneotherapy' comes from the Latin 'balneum' (bath). The term is classically used in (Eastern) European countries when natural mineral or thermal waters are used for bathing, drinking and inhalation. Recently a position paper was published with a proposal for, amongst others, a definition of balneotherapy (Gutenbrunner 2010). One of the core elements of balneotherapy is the use of (natural) mineral waters, gases and peloids (including packs = local application of peloids), often in health resorts (spas). In most European countries, balneotherapy often takes place at centres with thermal baths or seawater baths (Gutenbrunner 2010). In Israel, the main health resort area is located along the western shore of the Dead Sea. The unique environmental conditions in this area are considered beneficial for patients suffering from rheumatic disease (Sukenik 1994a).
In Homeric times, baths were applied primarily to cleanse and refresh. At the time of Hippocrates, bathing was regarded as more than a simple hygienic measure. It was considered beneficial in curing most illnesses (van Tubergen 2001). The Romans used water for treatment of orthopaedic conditions, but after the Roman era, spa therapy fell into disuse. In the sixteenth century, baths were rediscovered. Since that time, spa therapy has been practised continuously in the management of musculoskeletal conditions (Brosseau 2002; van Tubergen 2001; Verhagen 2007).
Balneotherapy is prescribed most often for patients with any form of arthritis, including fibromyalgia. Positive effects have been mentioned in the treatment of psoriasis as well (Brosseau 2002; Buskila 2001; Verhagen 2007).
Exercise in warm (tap) water is usually called 'hydrotherapy' or 'aquatic therapy'. This Cochrane review focuses on balneotherapy only, which consists of bathing in natural mineral or thermal waters, using mudpacks or doing both.
How the intervention might work
The mechanism by which balneotherapy might work is not clear. Water (thermal water, sea water) is generally used at a temperature of between 34°C and 36°C (Becker 2009; Gutenbrunner 2010). Hydrostatic force (Archimedes' principle) brings about relative pain relief by reducing loading (Becker 2009); water reduces gravity in painful and rheumatic joints. The warmth and buoyancy of water may block nociception by acting on thermal receptors and mechanoreceptors (Bender 2005). Warm water may also enhance blood flow, which is thought to help in dissipating algogenic chemicals, and may facilitate muscle relaxation (Kamioka 2010). Apart from these mechanical and thermal mechanisms, one should not undervalue the psychological mechanisms of the spa environment. The related mental relaxation may also play a role in pain relief (Brosseau 2002).
The aim of balneotherapy is to improve the range of joint motion, relieve muscle spasm, maintain or improve functional mobility, soothe pain and, as a consequence, relieve patients' suffering and help them feel well (Fam 1991; Gutenbrunner 2010; Jagger 1984; Sukenik 1994a).
Why is it important to do this review?
No cure for RA is known at present, so treatment often focuses on management of symptoms such as pain, stiffness and mobility. Treatment options include pharmacological interventions (Colebatch 2011; Hurkmans 2009; Marks 2011; Richards 2012a; Richards 2012b; Ruiz Garcia 2011; Singh 2009; Singh 2010a; Singh 2010b; Whittle 2011), physical therapy (Brosseau 2003, Han 2004) and balneotherapy (Verhagen 2008). Since our last publication of this Cochrane review (Verhagen 2008), several systematic reviews and meta‐analyses on the effectiveness of balneotherapy have been published (Falagas 2009; Forestier 2008; Kamioka 2010). These reviews either combine balneotherapy and hydrotherapy (Forestier 2008; Kamioka 2010) or combine different diseases (Falagas 2009).
Despite its popularity, reported scientific evidence on the effectiveness or efficacy of balneotherapy is sparse. This review evaluates the benefits and harms of balneotherapy in patients with RA.
Objectives
To perform a systematic review on the benefits and harms of balneotherapy in patients with rheumatoid arthritis in terms of pain, improvement, disability, tender joints, swollen joints and adverse events.
Methods
Criteria for considering studies for this review
Types of studies
Studies were eligible if they were randomised controlled trials (RCTs).
Types of participants
Participants had rheumatoid arthritis (RA), with definitive or classical RA as defined by the American Rheumatism Association (ARA) criteria of 1958 (Ropes 1958), the ARA/American College of Rheumatology (ACR) criteria of 1988 (Arnett 1988) or the ACR/EUropean League Against Rheumatism (EULAR) criteria of 2010 (Aletaha 2010), or by studies using the criteria of Steinbrocker (Steinbrocker 1949).
Types of interventions
Balneotherapy had to be the intervention under study, and had to be compared with another intervention or with no intervention. Balneotherapy is defined as bathing in natural mineral or thermal waters (e.g. mineral baths, sulphur baths, Dead Sea baths), using mudpacks or doing both.
Types of outcome measures
Major outcomes
The World Health Organization (WHO) and the International League Against Rheumatism (ILAR) determined in 1992 a core set of eight endpoints for clinical trials concerning patients with RA (Boers 1994). Major outcomes that we will consider are pain, improvement, disability, tender joints, swollen joints, withdrawals due to adverse events and serious adverse events.
Minor outcomes
Other outcomes that we considered include patient global assessment, physician global assessment, stiffness, range of motion, activities of daily living, quality of life, morning stiffness, walk time, hand grip strength and Ritchie index.
We considered all major outcomes and presented results in the 'Summary of findings' tables.
Search methods for identification of studies
Electronic searches
We searched the Cochrane 'Rehabilitation and Related Therapies' Field Register (to December 2014), the Cochrane Central Register of Controlled Trials (2013, Issue 1), MEDLIINE (1950 to December 2014), EMBASE (1988 to December 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to December 2014), the Allied and Complementary Medicine Database (AMED) (1985 to December 2014), PsycINFO (1806 to December 2014) and the Physiotherapy Evidence Database (PEDro) (to December 2014). We applied no language restrictions, but studies not reported in English, Dutch, Danish, Swedish, Norwegian, German or French are awaiting assessment.
We also searched the WHO International Clinical Trials Registry Platform for ongoing and recently completed trials.
In MEDLINE, the subject‐specific strategy was combined with the sensitivity‐ and precision‐maximising version of the Cochrane Highly Sensitive Search Strategy (Higgins 2011a) used to identify randomised trials in MEDLINE and modified for use in other databases.
Search strategies performed in MEDLINE, CENTRAL, EMBASE and CINAHL are presented in Appendix 1.
Searching other resources
We also searched the reference lists of articles and contacted experts in the field.
Data collection and analysis
Selection of studies
Initially, two review authors (SMAB‐Z, JL) independently selected trials by inspecting titles, keywords and abstracts to determine whether studies met the inclusion criteria regarding design, participants and interventions. We retrieved for final assessment full publications of studies of any possible relevance. Next, we used a standardised form to independently perform the final selection of trials to be included in the review. We resolved disagreements by consensus and, if necessary, by third party adjudication (APV).
Data extraction and management
Two review authors (JRC, JL) independently extracted data on trial methods, participants, interventions, types of outcome measures, duration of follow‐up, loss to follow‐up and results using a standardised data extraction form. We resolved disagreements by consensus and, if necessary, by third party adjudication (APV). We contacted trial authors when further information was required to complete the data extraction form.
Assessment of risk of bias in included studies
Two review authors (RAdB, HCWdV) independently assessed risk of bias by using the assessment tool developed by The Cochrane Collaboration (Higgins 2011a). This tool involves assessment of randomisation (sequence generation and allocation concealment), blinding (of participants, care providers and outcome assessors), completeness of outcome data, selection of outcomes reported and other sources of bias (baseline comparability, co‐interventions, compliance, timing of outcome measures). All items could be scored as having high, low or unclear risk of bias. We resolved disagreements by consensus; if disagreement persisted, a third review author (APV) made a final decision. We contacted trial authors if further information was required.
Measures of treatment effect
We presented various outcome measures separately. For dichotomous data, we expressed results, if possible, as risk ratios (RRs) with corresponding 95% confidence intervals (CIs). We calculated mean differences (MDs) or, when scales for outcome measures were dissimilar, standardised mean differences (SMDs) with 95% confidence intervals for continuous data (Lau 1997).
Unit of analysis issues
Treatment allocation was done at an individual level in all trials, and no cluster‐randomised or cross‐over trials were found, so the unit of analysis was the individual participant.
Dealing with missing data
When possible, we contacted trial authors to request missing data, and we performed intention‐to‐treat analyses to include all randomly assigned participants. For dichotomous data, we performed a worst‐case scenario when all missing people in the intervention group had a bad outcome, although none of the missing people in the control group had such an outcome. However for continuous data, when dropouts were identified, we used the actual number of participants contributing data at the relevant outcome assessment. Unless missing standard deviations could be derived from confidence intervals or standard errors (from the same study), we did not assume values for the purpose of presenting them in the analyses.
Assessment of heterogeneity
We assessed heterogeneity between pooled trials by using a combination of visual inspection of graphs and consideration of the I2 statistic (Higgins 2003). Substantial heterogeneity is defined as I2 greater than 50%.
Assessment of reporting biases
Available data are insufficient for assessment of publication bias via a prepared funnel plot, so publication bias cannot be assessed.
Data synthesis
We used RevMan Analyses (RevMan5) to analyse the data. In the previous review (Verhagen 2008), review authors did not pool data because the included trials were considered clinically heterogeneous in terms of study populations and interventions. Should pooling be possible with new trials included, we will pool results of comparable groups of trials by using a random‐effects model and 95% confidence intervals.
Subgroup analysis and investigation of heterogeneity
Preplanned stratified analyses included:
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trials comparing balneotherapy versus no treatment or waiting list controls;
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trials comparing different types of balneotherapy; and
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trials comparing balneotherapy versus other treatment(s) (e.g. exercise, oral medication).
Sensitivity analysis
A preplanned sensitivity analysis involved the risk of bias items of concealed randomisation and blinding.
'Summary of findings' table
The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system was used to evaluate the overall quality of evidence (Higgins 2011b). The quality of the evidence was based upon five domains and was downgraded by one level for each of these factors when encountered: (1) limitations in design, (2) indirectness of evidence (i.e. generalisability of findings), (3) unexplained heterogeneity or inconsistency of results (significant statistical heterogeneity (I2 > 50%) or inconsistent findings among studies, (4) imprecision (total number of participants < 300 for each outcome) and (5) high probability of publication bias. Two review authors (SMSB‐Z,APV) determined these factors. We considered single randomised studies (n < 300 for dichotomous outcomes and n < 400 for continuous outcomes) to be inconsistent and imprecise and to provide “low‐quality evidence”, which could be further downgraded to "very low‐quality evidence" for limitations in design (i.e. high risk of bias), indirectness or other considerations. We applied the following levels of quality of evidence.
-
High quality: Further research is very unlikely to change the level of evidence. Data are sufficient and have narrow confidence intervals. No reporting biases are known or suspected; all domains were fulfilled.
-
Moderate quality: Further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate; one of the domains was not fulfilled.
-
Low quality: Further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate; two of the domains were not fulfilled.
-
Very low quality: Great uncertainty surrounds the estimate; three of the domains were not fulfilled.
Results
Description of studies
Results of the search
A search conducted for this update resulted in 210 references, from which two review authors (JL, APV) independently selected 16 additional references on the basis of title and abstract. Of these, two studies were found to be eligible on the basis of full paper assessment and were included in this review (Codish 2005; Franke 2007); see study flow chart in Figure 1.
Study flow diagram.
Included studies
Final selection based on consensus resulted in inclusion of nine studies in this review, of which five were of Israeli origin, although they were written in English (Codish 2005; Elkayam 1991; Sukenik 1990a; Sukenik 1990b; Sukenik 1995).
Participants
A total of 579 participants were enrolled, and the number of participants in the intervention groups ranged from eight to 67 (see Characteristics of included studies). In six of the nine studies, the smallest study arm included fewer than 30 participants, meaning that most studies were underpowered. In seven studies, researchers used ARA criteria when selecting participants, and in two studies, they used the Steinbrocker criteria (Hall 1996; Yurtkuran 1999). All studies included participants with RA as defined by ARA or Steinbrocker criteria, although the severity of RA differed slightly between studies. When mentioned, the percentage of males was between 5% and 40%, and mean age ranged from 39 to 62.4 years.
Interventions
Six studies had two treatment arms, and the other three studies had four treatment arms. Only once was a placebo control used in comparison with mudpacks (Codish 2005). In two studies, a no‐treatment control group was used (Sukenik 1990b; Sukenik 1995). In both studies, participants were aware of the fact that they did not receive baths as treatment. In one other study, the drug treatment group was the control group (Yurtkuran 1999). In all but one study (Hall 1996), the intervention included mineral baths, and in one study, the intervention was given in combination with mudpacks (Elkayam 1991). Two studies evaluated Dead Sea baths (Sukenik 1990a; Sukenik 1995), and two studies evaluated the added value of radon over carbon dioxide in the bath (Franke 2000; Franke 2007).
In all studies, the baths were prepared at between 35°C and 38°C. All participants continued their medication during balneotherapy. One study mentioned standardised exercise therapy (Hall 1996), and in another study, relaxation exercises were allowed (Yurtkuran 1999).
All studies but one were performed at spa resorts; only Codish (Codish 2005) provided mudpacks (and placebo mudpacks) to be used at home.
Outcome measures
All studies used several outcome measures including pain and function. Often a standard set of outcome measures was used, such as duration of morning stiffness, 15‐meter walk time, hand grip strength, Ritchie index, severity of disease as assessed by participant or physician and laboratory variables. In two studies (Franke 2000; Hall 1996), investigators used a 'quality of life' instrument (Arthritis Impact Measurement Scales (AIMS) or AIMS2). Three studies (Codish 2005; Franke 2000; Yurtkuran 1999) reported response to treatment or improvement, but investigators in different studies defined it differently (see Characteristics of included studies).
The overall follow‐up period was three months; only two studies reported six‐month follow‐up (Franke 2000; Franke 2007).
Excluded studies
From the total search, 21 studies are awaiting assessment because of their language of publication (19 first review, two first update); 21 studies were excluded because they appeared not to be RCTs (16 first review, two first update and three second update); 18 were excluded because they did not concern RA (12 first review, two first update and four second update) and eight because of the outcome measures selected (one first review, one first update and six second update).
Risk of bias in included studies
Four studies described their randomisation procedure; three of these studies were considered to use a concealed randomisation procedure (Franke 2000; Franke 2007; Hall 1996) (Figure 2 and Figure 3).
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Blinding of the observer/outcome assessor is mentioned in all studies, but in several studies, the participant reported the main outcome, and it was unclear whether the participant was blinded, which means that we scored blinding of the outcome assessor as unclear (unclear risk of bias) (Hall 1996; Sukenik 1990b; Sukenik 1995; Yurtkuran 1999). Four studies mentioned blinding of the caregiver (Codish 2005;Franke 2000; Franke 2007; Sukenik 1990a), but the success of blinding was never evaluated.
Two studies were scored as having low risk of bias on ‘other biases’ because study authors clearly mentioned that groups were comparable at baseline, co‐interventions were comparable and compliance was acceptable (Franke 2000; Franke 2007).
Only three studies were considered to have no limitations in design, meaning a low risk of bias in most domains (Franke 2000; Franke 2007; Sukenik 1990a). In terms of the risk of bias assessment, the Kappa between two review authors appeared to be moderate at 0.68.
Effects of interventions
See: Summary of findings for the main comparison Balneotherapy compared with placebo for participants with rheumatoid arthritis; Summary of findings 2 Additional radon in carbon dioxide baths compared with carbon dioxide baths only for participants with rheumatoid arthritis; Summary of findings 3 Balneotherapy compared with drug treatment for participants with rheumatoid arthritis
Data presented in the papers, even after communication with the study authors, were too scarce to enable 'between‐group' analysis in almost half the studies. Also the studies used different interventions or comparison treatments and a wide variety of outcome measures; therefore interventions and outcome measures were considered heterogeneous.
One study assessed arms of balneotherapy (Yurtkuran 1999); only one participant complained of headache. In this study, most side effects were found in the control group (Cyclosporin A); between 4% and 16% of participants experienced various side effects such as gastrointestinal disturbance (one participant; 4%) and nephrotoxicity (four participants; 16%) (Yurtkuran 1999).
Trials comparing balneotherapy versus placebo or no treatment/waiting list controls
One study (n = 45) compared mudpacks versus placebo mudpacks for hand RA (Codish 2005).
We found no statistically significant differences between groups in terms of pain intensity (MD 0.50, 95% CI ‐0.84 to 1.84; absolute difference 0.5%), improvement (or ‘response rate’) (RR 0.96, 95% CI 0.54 to 1.70; absolute difference ‐2%) and number of tender joints (MD ‐4.60, 95% CI ‐8.72 to ‐0.48; absolute difference ‐16%) (Analysis 1.1; Analysis 1.2; Analysis 1.3; summary of findings Table for the main comparison). Therefore we conclude that very low‐level evidence (single study, downgraded by design) showed unclear benefit of mudpacks over placebo in hand RA in terms of pain, response rate and number of tender joints. Physical disability was not reported. Also no data were presented on improvement, withdrawals due to adverse events or serious adverse events.
Two studies (n = 76) included a control group receiving no treatment (Sukenik 1990b; Sukenik 1995). Both studies suffer from high risk of bias and low power; short‐term improvement was mentioned in all treatment groups compared with control groups for most outcome measures (see Characteristics of included studies). No data were provided on pain, improvement, physical disability, number of tender and swollen joints, withdrawals due to adverse events or serious adverse events. The study authors' conclusion of improvement was based on pre/post analysis. Data on harm or side effects were not reported.
Trials comparing different types of balneotherapy
Three studies compared mineral baths versus tapwater baths (Elkayam 1991; Franke 2000; Franke 2007). We were able to pool the data from two studies (n = 194) evaluating the effectiveness of additional radon in carbon dioxide baths (Franke 2000; Franke 2007).
We found no statistically significant differences post treatment and at three months in pain intensity on a VAS, but a statistically significant difference in pain in favour of additional radon at six‐month follow‐up only, with a difference of 9.6 mm on a 100‐mm VAS (95% CI 1.6 to 17.6). Both effect estimates show no clinically relevant differences (> 15%) (Analysis 2.1; summary of findings Table 2).
We found no differences post treatment and at three months in terms of improvement in pain frequency on a 4‐point scale (no, sporadic, daily, continuous) or improvement in one or more categories, but a significant difference of only 30% in favour of additional radon at six‐month follow‐up (RR 2.3, 95% CI 1.1 to 4.7) (Analysis 2.2; summary of findings Table 2).
For all other outcomes (physical disability, tender joints, swollen joints, withdrawals due to adverse events and serious adverse events), no data were provided.
Therefore we conclude that moderate‐level evidence (downgraded because of imprecision (low power)) shows unclear benefit in terms of pain at end of treatment and at three‐month follow‐up, but benefit of additional radon in carbon dioxide baths for the treatment of participants with RA at six months, although the clinical relevance of this benefit is small. We found low‐level evidence (single study) of unclear benefit for improvement at end of treatment and at three‐month follow‐up, but benefit of additional radon in carbon dioxide baths in the treatment of patients with RA at six months.
Two studies (n = 76) compared Dead Sea salt baths versus normal salt baths (Sukenik 1990a) or sulphur baths (Sukenik 1995), and another study (n = 30) compared sulphur baths versus mudpacks (Sukenik 1990b). All three studies did not provide sufficient data on pain, improvement, physical disability, number of tender and swollen joints, withdrawal due to adverse events and serious adverse events for the analysis. The authors of original studies mentioned short‐term improvement in all treatment groups on most outcome measurements, but a more profound effect in the groups receiving mineral baths. All studies were of low power, performed a pre/post analysis and presented only point estimates.
Trials comparing balneotherapy versus other treatments (e.g. exercise, oral medication)
In one study (n = 35 in each study arm), 'balneotherapy' (seated immersion) was compared with hydrotherapy (exercise in water), land exercise or relaxation therapy (Hall 1996). Here balneotherapy was performed with tapwater at 36°C (Analysis 3.1).
We found no statistically significant differences in pain (MD 0.05, 95% CI ‐0.32 to 0.42) and physical disability (MD ‐0.70, 95% CI ‐1.50 to 0.10). No data were provided on improvement, tender joints, swollen joints, withdrawal due to adverse events or serious adverse events.
Therefore we conclude that a very low level of evidence (single study and downgraded because of limitations in design (high risk of bias)) shows unclear benefit of tapwater bathing over relaxation, exercise or hydrotherapy.
In another study (n = 57), balneotherapy was compared with drug therapy (Cyclosporin A (CsA) 3.5 mg/kg) (Yurtkuran 1999). We found no statistically significant differences in terms of pain (0 to 100 VAS) (MD 8, 95% CI ‐17.54 to 1.54) or swollen joints (MD 1.50, 95% CI ‐1.25 to 4.25) (Analysis 3.2; summary of findings Table 3). We found a statistically significant benefit of mineral baths in terms of overall improvement at eight weeks of 54% (RR 2.35, 95% CI 1.44 to 3.83) (Analysis 3.3) and significant benefit of Cyclosporin A at eight weeks in terms of the number of tender joints (MD 8.9, 95% CI 3.8 to 14) (Analysis 3.4; summary of findings Table 3). For all other outcome measures (physical disability, withdrawal due to adverse events and serious adverse events), no data were provided.
Very low‐level evidence (single study and downgraded because of limitations in design (high risk of bias)) suggests some benefit of mineral baths over Cyclosporin A concerning overall improvement, and of Cyclosporin A over mineral baths in terms of the number of swollen joints.
Discussion
Summary of main results
This review evaluated the benefits and harms of balneotherapy in patients with RA. Concerning pain, number of tender joints, ‘response rate’ or improvement, no statistically significant differences were found between mudpacks for the hand and placebo mudpacks (very low level of evidence) or for bathing with tapwater over relaxation, exercise or hydrotherapy (very low level of evidence). Harms were not reported for this comparison.
In terms of pain, some benefit has been associated with additional radon in carbon dioxide baths for the treatment of patients with RA, but the clinical relevance of this benefit is small (moderate level of evidence). Regarding all other outcome measures (improvement, disability, tender joints, swollen joints, withdrawal due to adverse events or serious adverse events), we conclude that the benefit of either form of balneotherapy over another is inconclusive.
For pain, a very low level of evidence of unclear benefit was found. For overall improvement, we found some benefit of balneotherapy over drug treatment (very low level of evidence). In this comparison, withdrawals due to adverse events were not reported.
Overall completeness and applicability of evidence
Rheumatoid arthritis (RA) is a chronic, progressive and disabling disease that has great impact on quality of life. When balneotherapy is evaluated, the outcome measures used and the follow‐up period chosen should be adequate. The main aims of balneotherapy are to maintain or improve functional mobility, soothe pain and let patients feel well. Often a standard set of outcome measures was used. In daily life, patients are trying to deal with pain by using coping strategies. Pain (often assessed by the patient) was reported as an outcome measure in the Methods sections of most studies, but results were seldom reported. A 'quality of life' assessment was reported in only two studies (Franke 2000; Hall 1996). This is surprising because one of the aims of balneotherapy, or therapy for patients with chronic disease in general, is to improve health‐related 'quality of life'. The question can be raised whether the outcome measures used in most studies were specific and responsive enough to enable measurement of treatment effect. Also the follow‐up period seems to be rather short. Positive effects of spa therapy have been found in patients with ankylosing spondylitis even after 40 weeks of follow‐up (van Tubergen 2001).
We noted heterogeneity of the intervention 'balneotherapy'. Once balneotherapy consisted of tapwater, once as mineral baths (38°C, daily for 20 minutes) + mudpacks (for 20 minutes), twice as radon/carbon dioxide baths (15 times in four weeks, for 20 minutes), twice as Dead Sea baths (daily for 20 to 30 minutes), twice as sulphur baths (daily for 20 minutes), once as a combination of Dead Sea and sulphur baths, once as a combination of sulphur baths + mudpacks (see table of included studies) and once as only mudpacks. This makes it difficult to determine what the most effective form of balneotherapy is, or even whether an essential element (minerals) in the water is responsible for its effectiveness.
Quality of the evidence
Unfortunately, most studies showed methodological flaws resulting in high risk of bias. Also data presentation was often lacking. When information concerning trial design, especially regarding strategies to avoid bias, is lacking, we could not exclude possible bias in the trial. Therefore, a robust analysis of the effectiveness of balneotherapy cannot be presented.
Potential biases in the review process
Our review might very well suffer from selection bias based on language. We found several studies that were presented in Hebrew, Japanese or one of the Eastern European languages. Often the English abstract was lacking information about the design of the study. These studies are all awaiting assessment.
We used the criteria of the Cochrane Back Review Group (CBRG) for risk of bias assessment (Furlan 2009). This tool is a slightly extended version of the one described in the Cochrane Handbook for Systematic Reviews of Interventions, although with some sub‐items in the different domains, easing the risk of bias assessment. In previous versions of the review, we used the Delphi list, which is comparable with the risk of bias assessment tool of the CBRG (Verhagen 1998). Therefore we observed no major differences concerning risk of bias assessment between the previous version and the current version of the review. Overall this risk of bias assessment tool can be regarded as a reliable and valid instrument (Furlan 2009; Verhagen 2001). Nevertheless misclassification is always a possibility.
The 'spa environment' is an important factor in treatment results (Balint 1993; Sukenik 1994a). Many factors may contribute positively to reported effects (Fam 1991), such as changes in environment, the 'spa scenery', absence of (house)work duties, physical and mental relaxation, the non‐competitive atmosphere with similarly suffering companions, physical therapy and so forth. As such, any benefit of the spa could perhaps be attributed also to the effects of factors unrelated to the "water" therapy per se.
Agreements and disagreements with other studies or reviews
The conclusion of this review that evidence is still insufficient to show the effectiveness of balneotherapy is consistent with the conclusion of other reviews (Brosseau 2002; Kamioka 2010; Karagülle 2004). Although the selection criteria differ between reviews, all review authors conclude that poor methodological quality and scarce data presentation make it impossible to draw firm conclusions. The more recent studies are of better methodological rigour, but additional studies are needed.
Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 Balneotherapy versus placebo or no treatment, Outcome 1 Pain intensity.
Comparison 1 Balneotherapy versus placebo or no treatment, Outcome 2 Improvement.
Comparison 1 Balneotherapy versus placebo or no treatment, Outcome 3 Tender joints.
Comparison 1 Balneotherapy versus placebo or no treatment, Outcome 4 Swollen joints.
Comparison 2 Additional radon in carbon dioxide versus carbon dioxide alone, Outcome 1 Pain intensity.
Comparison 2 Additional radon in carbon dioxide versus carbon dioxide alone, Outcome 2 Improvement.
Comparison 3 Balneotherapy versus other treatments, Outcome 1 Versus relaxation.
Comparison 3 Balneotherapy versus other treatments, Outcome 2 Versus drug treatment.
Comparison 3 Balneotherapy versus other treatments, Outcome 3 Versus drug treatment.
Comparison 3 Balneotherapy versus other treatments, Outcome 4 Versus drug treatment.
| Balneotherapy compared with placebo for participants with rheumatoid arthritis | ||||||
| Patient or population: participants with rheumatoid arthritis | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Placebo | Balneotherapy | |||||
| Pain intensity | Mean pain intensity in control groups was | Mean pain intensity in intervention groups was | 45 | ⊕⊝⊝⊝ | MD 0.50 (95% CI ‐0.84 to 1.84) Absolute difference 0.5% (95% CI ‐0.84% to 1.84%) Relative percent change 1% (95% CI ‐2% to 4%) No statistically significant or clinically relevant difference | |
| Improvement measures (> 30% reduction in number of swollen joints, > 30% reduction in number of tender joints, > 20% improvement in patient VAS for severity of pain and > 20% improvement in physician VAS) | 522 per 1000 | 501 per 1000 | RR 0.96 | 45 | ⊕⊝⊝⊝ | Absolute difference ‐2% (95% CI ‐31% to 27%) Relative percent change 5% (95% CI ‐42% to 70%) No statistically significant or clinically relevant difference |
| Physical disability Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Tender joints Number of painful joints Scale from 0 to 28 Follow‐up: 3 months | Mean number of tender joints in control groups was | Mean number of tender joints in intervention groups was | 45 | ⊕⊝⊝⊝ | MD ‐4.60 (95% CI ‐8.72 to ‐0.48) Absolute difference ‐16% (95% CI ‐31% to 2%) Relative percent change ‐37% (95% CI ‐70% to ‐4%) NNTB 32 (95% CI 10 to 717) | |
| Swollen joints Number of swollen joints Scale from 0 to 28 Follow‐up: 3 months | Mean number of swollen joints in control groups was | Mean number of tender joints in intervention groups was | 45 | ⊕⊝⊝⊝ | MD 0.60 (95% CI ‐0.90 to 2.10) Absolute difference 2% (95% CI ‐3% to 8%) Relative percent change 32% (95% CI ‐47% to 110%) No statistically significant or clinically relevant difference | |
| Withdrawal due to serious adverse events Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Adverse events Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| *The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aDowngraded because of imprecision. | ||||||
| Additional radon in carbon dioxide baths compared with carbon dioxide baths only for participants with rheumatoid arthritis | ||||||
| Patient or population: participants with rheumatoid arthritis | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Carbon dioxide baths only | Additional radon in carbon dioxide baths | |||||
| Pain intensity | Mean change in pain intensity in control groups was | Mean change in pain intensity in intervention groups was | 194 | ⊕⊕⊕⊝ | MD ‐4.49 (95% CI ‐13.41 to 4.44) Absolute difference 4.5% (95% CI ‐13.4 to 4.4) No statistically significant or clinically relevant difference | |
| Pain intensity | Mean change in pain intensity in control groups was | Mean change in pain intensity in intervention groups was | 194 | ⊕⊕⊕⊝ | MD ‐9.59 (95% CI ‐17.57 to ‐1.6) Absolute difference 9.5% (95% CI ‐17.5 to ‐1.6) Statistically significant but not clinically relevant difference | |
| Improvement | 267 per 1000 | 367 per 1000 | RR 1.38 (0.64 to 2.93) | 60 | ⊕⊕⊝⊝ | Absolute difference 10% (95% CI ‐13% to 33%) Relative percent change 38% (95% CI ‐36% to 22%) No statistically significant or clinically relevant difference |
| Improvement | 233 per 1000 | 533 per 1000 | RR 2.29 (1.1 to 4.74) | 60 (1 study) | ⊕⊕⊝⊝ | Absolute difference 30% (95% CI 10% to 60%) Relative percent change 129% (95% CI 10% to 474%) Statistically significant and clinical relevant difference |
| Physical disability Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Tender joints Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Swollen joints Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Withdrawal due to serious adverse events Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Adverse events Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| *The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aDowngraded because of imprecision. | ||||||
| Balneotherapy compared with drug treatment for participants with rheumatoid arthritis | ||||||
| Patient or population: participants with rheumatoid arthritis | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Drug treatment ‐ Cyclosporin A | Balneotherapy | |||||
| Pain intensity | Mean pain intensity in control groups was | Mean pain intensity in intervention groups was | 57 | ⊕⊝⊝⊝ | MD 9.64 (95% CI ‐1.66 to 20.94) Absolute difference 10% (95% CI ‐2% to 21%) Relative percent change 53% (95% CI ‐9% to 116%) No statistically significant or clinically relevant difference | |
| Improvement | 400 per 1000 | 940 per 1000 | RR 2.35 (1.44 to 3.83) | 57 | ⊕⊝⊝⊝ | Absolute difference 54% (95% CI 33% to 75%) Relative percent change 135% (95% CI 44% to 283%) NNTB 2 (95% CI 2 to 3) |
| Physical disability Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Tender joints Number of tender joints Scale from 0 to 28 Follow‐up: 8 weeks | Mean number of tender joints in control groups was | Mean number of tender joints in intervention groups was | 57 (1 study) | ⊕⊝⊝⊝ | MD 8.90 (95% CI 3.83 to 13.97) Absolute difference 31% (95% CI 17% to 50%) Relative percent change 228% (95% CI 98% to 358%) NNTB 22 (95% CI 8 to 96) | |
| Swollen joints Number of swollen joints Scale from 0 to 28 Follow‐up: 8 weeks | Mean number of swollen joints in control groups was | Mean number of tender joints in intervention groups was | 57 (1 study) | ⊕⊝⊝⊝ | MD 1.50 (95% CI ‐1.25 to 4.25) Absolute difference 5% (95% CI ‐4% to 15%) Relative percent change 79% (95% CI ‐66% to 224%) No statistically significant or clinical relevant difference | |
| Withdrawal due to serious adverse events Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| Adverse events Not reported | See comment | See comment | Not estimable | ‐ | See comment | Not reported |
| *The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aDowngraded because of single study. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Pain intensity Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 1.1 End of treatment | 1 | 45 | Mean Difference (IV, Random, 95% CI) | 0.20 [‐1.18, 1.58] |
| 1.2 1‐Month follow‐up | 1 | 45 | Mean Difference (IV, Random, 95% CI) | ‐0.40 [‐1.74, 0.94] |
| 1.3 3‐Month follow‐up | 1 | 45 | Mean Difference (IV, Random, 95% CI) | 0.5 [‐0.84, 1.84] |
| 2 Improvement Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.1 End of treatment | 1 | 45 | Risk Ratio (M‐H, Random, 95% CI) | 0.97 [0.57, 1.63] |
| 2.2 1‐Month follow‐up | 1 | 45 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.66, 1.65] |
| 2.3 3‐Month follow‐up | 1 | 45 | Risk Ratio (M‐H, Random, 95% CI) | 0.96 [0.54, 1.70] |
| 3 Tender joints Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 3.1 End of treatment | 1 | 45 | Mean Difference (IV, Random, 95% CI) | ‐6.0 [‐9.57, ‐2.43] |
| 3.2 1‐Month follow‐up | 1 | 45 | Mean Difference (IV, Random, 95% CI) | ‐5.1 [‐8.58, ‐1.62] |
| 3.3 3‐Month follow‐up | 1 | 45 | Mean Difference (IV, Random, 95% CI) | ‐4.60 [‐8.72, ‐0.48] |
| 4 Swollen joints Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 4.1 End of treatment | 1 | 45 | Mean Difference (IV, Random, 95% CI) | 0.10 [‐1.58, 1.78] |
| 4.2 1‐Month follow‐up | 1 | 45 | Mean Difference (IV, Random, 95% CI) | 0.10 [‐1.45, 1.65] |
| 4.3 3‐Month follow‐up | 1 | 45 | Mean Difference (IV, Random, 95% CI) | 0.60 [‐0.90, 2.10] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Pain intensity Show forest plot | 2 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 1.1 Additional radon, post treatment | 2 | 194 | Mean Difference (IV, Random, 95% CI) | 1.68 [‐4.64, 7.99] |
| 1.2 Additional radon, 3 months | 2 | 194 | Mean Difference (IV, Random, 95% CI) | ‐4.49 [‐13.41, 4.44] |
| 1.3 Additional radon, 6 months | 2 | 194 | Mean Difference (IV, Random, 95% CI) | ‐9.59 [‐17.57, ‐1.60] |
| 2 Improvement Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.1 Additional radon, post treatment | 1 | 60 | Risk Ratio (M‐H, Random, 95% CI) | 1.27 [0.69, 2.33] |
| 2.2 Additional radon, 3 months | 1 | 60 | Risk Ratio (M‐H, Random, 95% CI) | 1.38 [0.64, 2.93] |
| 2.3 Additional radon, 6 months | 1 | 60 | Risk Ratio (M‐H, Random, 95% CI) | 2.29 [1.10, 4.74] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Versus relaxation Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 1.1 Pain post treatment | 1 | 70 | Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.01, 0.61] |
| 1.2 Pain at follow‐up | 1 | 70 | Mean Difference (IV, Random, 95% CI) | 0.05 [‐0.32, 0.42] |
| 1.3 Physical activity post treatment | 1 | 70 | Mean Difference (IV, Random, 95% CI) | ‐0.5 [‐1.34, 0.34] |
| 1.4 Physical activity at follow‐up | 1 | 70 | Mean Difference (IV, Random, 95% CI) | ‐0.70 [‐1.50, 0.10] |
| 2 Versus drug treatment Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 2.1 Pain at 4 weeks | 1 | 57 | Mean Difference (IV, Random, 95% CI) | ‐8.0 [‐17.54, 1.54] |
| 2.2 Pain intensity at 8 weeks | 1 | 57 | Mean Difference (IV, Random, 95% CI) | 9.64 [‐1.66, 20.94] |
| 3 Versus drug treatment Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 3.1 Improvement at 8 weeks | 1 | 58 | Risk Ratio (M‐H, Random, 95% CI) | 2.35 [1.44, 3.83] |
| 4 Versus drug treatment Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 4.1 Tender joints at 8 weeks | 1 | 57 | Mean Difference (IV, Random, 95% CI) | 8.9 [3.83, 13.97] |
| 4.2 Swollen joints at 8 weeks | 1 | 57 | Mean Difference (IV, Random, 95% CI) | 1.5 [‐1.25, 4.25] |
