Introduction

Rheumatoid arthritis (RA) is an auto-immune and systemic condition characterized mainly by joint inflammation, which causes pain, swelling and stiffness, and leads, in the long-term, to joint destruction, disability and increased mortality.1 The disease is associated with important negative consequences in almost all domains of physical and emotional wellbeing, including sleep disturbances, anxiety and depression.2,3

The current paradigm for the management of RA is epitomized by the treat-to-target strategy which establishes that remission, or at least low disease activity, should be pursued and achieved as early and consistently as possible.4,5 This target is defined on the basis of number of tender and swollen joints counts, levels of acute phase reactants and global assessments of disease activity by patient and/or physician, integrated into composite indices of disease activity.6

As a result of novel treatment strategies and drugs, a marked improvement in the results of RA management has been observed, regarding both the inflammatory process and impact of disease. However, a considerable proportion of patients with RA do not achieve clinical remission7 and even those who do, still report significant levels of disease impact, as assessed by instruments commonly described as patient-reported outcomes (PROs).3,8 According to patients, this impact is felt mainly in seven domains: pain, functional disability, fatigue, emotional wellbeing, sleep, coping, and physical wellbeing. It is, naturally, mandatory that disease impact is assessed and targeted by treatment, in parallel with the biological disease process.9,10

Once inflammation has been abrogated, the improvement of the impact of disease cannot be pursued by additional immunosuppressive therapy; adjunctive interventions targeting the uncontrolled domains of disease impact will be needed. Optimal care of patients with RA requires, therefore, an integrated approach including both pharmacologic and nonpharmacologic interventions7 seeking improvement in each and every domain, ideally in the context of a multidisciplinary team.11-13 Many nonpharmacologic treatments are available, such as patient counselling, advice and support,7,14-16 occupational therapy,17 cognitive behavioral therapy and other psychological interventions,18 physical interventions (exercise, physical activity, psychotherapy etc.), and more.19

Several systematic reviews summarize the available evidence on the effect of nonpharmacological interventions for patients with RA. In many cases, the evidence was considered insufficient to demonstrate effectiveness.14,15,19 Several gaps were identified in the evidence, because most of the reviews, in addition to being poorly reported and having significant methodological flaws,7,20 did not encompass the effects of modern treatments and strategies, which have changed the face of RA and the needs of patients. Even the criteria for classifying the disease have changed with time.21,22 The information about implemented and evaluated interventions and their characteristics, contexts of application, and health professionals in charge lacks systematization which hinders the implementation of the interventions in practice. Furthermore, several domains of the impact of the disease have not yet been explored, such as emotional and physical wellbeing.

A structured overview of the available information, including its quality and limitations, is clearly needed by patients, healthcare professionals and researchers in order to improve clinical practice, set priorities for research and foster development in this field. This would be achieved best through an umbrella review. The only one available had a limited scope (pain, function and patient global assessment) and was published in 2007,19 well before the updated classification criteria for RA22 and the treat-to-target strategy were in place.4

A preliminary search of the JBI Database of Systematic Reviews and Implementation Reports, the Cochrane Database of Systematic Reviews, PROSPERO, MEDLINE and CINAHL revealed that currently there is no other umbrella review (published or in progress) on this topic. Therefore, and since it is expected that the use of non-pharmacological and non-surgical interventions can reduce the impact of disease, the objective of this review is to understand the best available evidence, evaluate its quality and provide an up-to-date synthesis to inform healthcare professionals.

Inclusion criteria

Participants

This umbrella review will only consider existing systematic reviews that include adult patients satisfying current RA criteria,21,22 aged 18 years or over. Patients with other concomitant musculoskeletal diseases will be excluded.

Intervention

This review will consider systematic reviews that evaluate the effectiveness of non-pharmacological and/or non-surgical interventions in adult patients diagnosed with RA aiming to reduce its impact as a single intervention or multiple non-pharmacological and/or non-surgical interventions. For this purpose, it is considered that non-pharmacological interventions include, but are not limited to, any treatment that is not a registered drug,14 such as physical activity and exercise; occupational therapy; electro-physical modalities like thermotherapy, electrotherapy, and others; manual therapies like massage, orthoses, aids, devices and adaptations of physical environment, and others; and psychosocial interventions. Non-surgical interventions were considered to be all interventions not related in any way to surgery. There are no limitations to frequency/intensity/who delivers the intervention.

Comparator

This umbrella review will consider systematic reviews that compare the intervention to placebo, or to usual care.

Outcomes

This umbrella review will consider systematic reviews that include the following outcomes measures:

i. Primary outcomes: impact of disease, measured individually in at least one of the following domains: pain, functional disability, fatigue, emotional wellbeing, sleep, coping and physical wellbeing by validated instruments [e.g. Visual Analog Scale, Health Assessment Questionnaire, Functional Assessment of Chronic Illness Therapy, Rheumatoid Arthritis Impact of Disease (RAID)].

ii. Secondary outcomes: global impact of disease, measured collectively by the RAID,9,10 and/or global quality of life; measured by validated instruments (e.g. 36-Item Short Form Survey, EuroQol- 5 Dimension).23

Context

There are no context constrains in this umbrella review.

Types of studies

This umbrella review will consider quantitative systematic reviews with or without meta-analysis, comprehensive systematic reviews or mixed methods (only quantitative elements).

Systematic reviews that meet the following criteria will be considered for inclusion: having a clear articulated and comprehensive search strategy using multiple databases and having evidence of critical appraisal and assessment of risk of bias. In case of doubt due to unclear inclusion criteria, authors will be contacted for confirmation before exclusion. This review will exclude general literature reviews, primary research and qualitative reviews.

Systematic reviews published and unpublished from 2010 in English, French, Spanish and Portuguese language will be considered for inclusion. The criteria for classifying the disease were changed in 2010 to include patients in earlier stages of the disease and the impact of disease has changed dramatically in recent years due to more effective drug treatment.7,22

Methods

The Joanna Briggs Institute methodology for umbrella reviews will be used to complete this review.24

Search strategy

The search strategy aims to find both published and unpublished systematic reviews. A three-step search strategy will be utilized in this review.

An initial search, limited to PubMed and CINAHL has been undertaken to identify articles on this topic, followed by analysis of the text words contained in the titles or/and abstracts, and of the index terms used to describe these articles. This informed the development of a search strategy including identified keywords and index terms which will be tailored for each information source. A proposed search strategy for the PubMed database is provided in Appendix I.

A second search using all identified keywords and index terms will then be undertaken across all included databases, after appropriate adaptation for each included information source. Finally, the reference lists of all studies selected for critical appraisal will be searched for additional studies.

Information sources

The following will be searched: CINAHL Plus with Full Text, PubMed, Cochrane Database of Systematic Reviews, Scopus, Embase, PsycINFO, PEDro, Epistemonikos, JBI Database of Systematic Reviews and Implementation Reports, the PROSPERO register, Campbell Collaboration Library of Systematic Reviews.

The search for unpublished studies and gray literature will include: RCAAP - Repositorio Cientifico de Acesso Aberto de Portugal and OpenGrey - System for Information on Grey Literature in Europe.

Study selection

Following the search, all identified citations will be uploaded into EndNote VX7 (Clarivate Analytics, PA, USA) and duplicates removed. Titles and abstracts will then be screened by two independent reviewers (ES and AM) to assess eligibility according to the inclusion criteria for the review. The full article will be retrieved for all studies that meet or could potentially meet these inclusion criteria, and their citation details will be imported into the Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information (JBI SUMARI) (Joanna Briggs Institute, Adelaide, Australia). Based on full texts, two reviewers (ES and AM) will independently examine whether the studies conform to the inclusion criteria. Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer (CD).

Full text studies that do not meet the inclusion criteria will be excluded and reasons for exclusion will be provided in an appendix in the final systematic review report.

The results of the search will be reported in full in the final report and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram.25

Assessment of methodological quality

Eligible studies will be assessed by two independent reviewers (ES and AM) for methodological validity prior to inclusion in the review, using a standardized critical appraisal instrument from the Joanna Briggs Institute (JBI Critical Appraisal Checklist for Systematic reviews and Research Syntheses).24 Authors of papers will be contacted to request missing or additional data for clarification, where required. Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer (CD). The results of critical appraisal will be reported in narrative form and in a table. The decision to include a review will be based on a pre-determined score of 4 or more (established as a criterion of quality systematic reviews by the authors). The quality of each review will be eligible based on the following cut-offs: 0-3 will be considered a very low-quality score; 4-6 will be considered a low-quality score; 7-9 will be considered a moderate-quality score; and 10-11 will be considered a high-quality score. Reasons for not applying these criteria will be specified.

Data extraction

Data will be extracted from the selected studies as described above, by two independent reviewers (ES and AM) using the standardized data extraction tool in JBI SUMARI.26 The data extracted will include specific details about the type of review, countries where the primary studies were conducted, databases, search timeframes, number of studies included in the review, participants (number, age, comorbidities), type(s) of intervention(s) (including duration and frequency), outcomes of significance (types and characteristics), outcome measures, inclusion/exclusion criteria, methods of analysis, heterogeneity, effect size and, if provided, confidence intervals. Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer (CD). Authors of papers will be contacted to request missing or additional data, where required.

Data synthesis

The studies will be analyzed in separate categories based on the domain of outcome measure. The findings will be tabulated and accompanied by a narrative synthesis to address the review objective and specific question. The overall effect sizes and a clear description of the non-pharmacological intervention(s) will be presented to support the interpretation. The previous referred tables will include a high level of detail for each systematic review, such as including the number of studies, total number of participants and its specificities, assessment tool, heterogeneity, and complete information about the nonpharmacological intervention(s). The overlap of original research studies between systematic reviews will be clearly indicated and expressed as percentage to avoid double counting. Where possible, the sensitivity of the review findings will be considered based on the determinants of its quality, as assessed by critical appraisal to explore the consequences of synthesizing reviews of differing quality. The results of the umbrella review will be provided in an "Evidence Summary" table that includes the intervention, the included systematic review(s) and a simple visual indicator of the effectiveness of the intervention using the three colors of the traffic light: a beneficial or effective intervention (green), no effect or difference compared to a control treatment (orange) and a detrimental intervention or one that is less effective than a control treatment (red).24

Assessing certainty in the findings

The Grading of Recommendations, Assessment, Development and Evaluation (GRADE)27 approach for grading the certainty of evidence will be followed and a Summary of Findings (SoF) will be created using GRADEPro GDT software (McMaster University, ON, Canada), where possible. A four-point rating scale will be used to rate the quality of the evidence: high, moderate, low and very low. The quality of evidence will be classified by evaluating it using the following criteria: methodological limitations, consistency, risk of bias and relevance to the study population.

Acknowledgments

The authors would like to acknowledge the support provided by Health Sciences Research Unit: Nursing (UICISA: E), hosted by the Nursing School of Coimbra (ESEnfC).

This review will contribute towards a PhD in Nursing Sciences for the first author, ES.

Appendix I: Search strategy

Search strategy for PubMed conducted on 28 June 2018.

References