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Egyptian guidelines for the treatment of Rheumatoid Arthritis — 2022 update



Busy rheumatologists, and busy patients as well as policy makers, require accurate, succinct, transparent, easily digested summaries of evidence and recommendations for management. Our objective was to develop an up-to-date evidence-based, consensus, clinical practice guidelines for treat-to-target management of rheumatoid arthritis in adults.


Ninety-four (94.7%) of the expert committee completed the 2-round e-Delphi surveys. A total of 33 recommendation items, addressing the main rheumatoid arthritis (RA) domains, were identified. The level of agreement (rate 7–9), for the statements which reached consensus, ranged from 85 to 100%. Consensus was achieved on the wording of all the clinical practice guidelines identified by the scientific committee. A management algorithm for the management of rheumatoid arthritis have been developed.


These updated recommendations reflect the most recent evidence for the management of RA. It also outlines the multidisciplinary team role in enhancing the RA patients’ care. The recommendations offer strategies to achieve optimum treat-to-target outcomes. However, standards of care are defined based on the clinical data obtained for individual patients and are prone to modification. High-quality, broad scope evidence-based clinical practice guidelines offer a path for bridging the gap between best practice, policy, local settings and patients’ choice.


Since the publication of the original Egyptian recommendations for treatment of rheumatoid arthritis (RA) [1], a chronic inflammatory disease that causes joint pain, swelling, stiffness and impaired function, there has been a dramatic expansion of the available treatment options for the disease. At the same time, healthcare professionals and researchers are attaining new experiences and knowledge about the efficacy as well as safety of those treatment modalities which warrant further consideration of the recommended management algorithm. In concordance, novel measures of imaging modalities and patient educational tools [2] give the patients more information, allowing them to be more informed and involved in the shared decision-making process.

Although the main target of these guidelines is primarily rheumatologists and aims to make informed decisions about patients’ management, they are also valuable for people living with RA as well as health policymakers. In 2020, the Egyptian health authorities have launched a nationwide Universal Health Insurance System, aiming to ensure that all Egyptians have comprehensive health care for all family members in the ‘New Republic’ [3]. Setting up guidelines for management plays a vital role in the patients’ management process. The Egyptian Academy of Rheumatology launched the clinical, evidence-based guidelines (CEG) initiative protocol which was accepted by the local ethical committee. The overarching principle was to produce an up-to-date evidence-based consensus, clinical practice recommendations for treat-to-target management of the different rheumatic disorders. Therefore, an update to the earlier published recommendations for management of rheumatoid arthritis patients was required, including a critical analysis and evaluation of the more recent literature.



A multistep process strategy was adopted to develop the RA evidence-based, consensus management recommendations. The CEG guideline development process protocol was the standard based on which study design was formulated. The consensus was achieved based on the current scientific evidence and clinical knowledge. The aim was to determine the extent to which experts agree about a particular issue, with the ultimate goal of providing a unified expert opinion. The manuscript followed the guidelines for reporting systematic reviews and meta-analyses [4].

Study teams

Core team

To supervise, coordinate, and assist with developing the scope of the project and initial clinical questions, nominating the expert panel and drafting the manuscript. The core team also shared in identifying the project’s scope and the PICOT key questions addressed for this update.

Key questions used to develop the guideline

This management recommendations were centred on a sequence of organized key clinical questions that outline the targeted patients, the intervention, investigation, the comparison(s) used, the outcomes used to measure efficacy, effectiveness, or risk as well as time (PICOT) [5]. The evidence to respond to the key questions was gathered according to the following phases: the clinical questions formulation, configuring the questions, check for the evidence, critical analysis and assortment of evidence, results presentation, and guideline statements. These questions, shown in Table 1, formed the foundation of the systematic review search and subsequently the clinical standards for patients’ care.

Table 1 Levels of evidence

Literature review team

Led by an experienced literature review consultant, the review team reviewed full-text publications and rated the quality of evidence. Literature was also searched for best practice recommendations for joint imaging. This search for best practice evidence was based on the specific core items and domains included in the clinical research questions addressing the different aspects of RA management. An expert in methodology helped in conducting the literature review.

Data sources

To acquire best practice evidence for clinical recommendations development, the PubMed/ MEDLINE, Embase and Cochrane databases were searched. Based on the outcomes of the systematic review and their own clinical experience, the committee compiled a comprehensive list of proposals for the management of RA. The quality and level of evidence [6, 7] were also identified for each category according to the Oxford Centre for Evidence-based Medicine (CEBM) system [7].

Study selection

The boundaries of the systematic review were set according to the inclusion and exclusion criteria aiming at identifying the relevant studies.

Inclusion criteria

Eligibility criteria were based on the PICO approach, study design, and date.

Inclusion criteria included the following:

  1. (a)

    Manuscripts published as guidelines

  2. (b)

    Guidelines providing endorsements on RA general management of RA

  3. (c)

    Guidelines including a range of different medical therapies

  4. (d)

    Guidelines published from January 2010 to May 2022

  5. (e)

    Guidelines published in English

  6. (f)

    Systematic reviews, randomized controlled trials (RCTs), uncontrolled trials, observational studies including cohort, case control and cross-sectional studies or those where economic evaluation was made

The included publications should include the identification criteria of classification, evidence and recommendations. Also, the formal process for developing the management recommendations (Delphi exercise, panel conference) should be delineated.

Exclusion criteria

The exclusion criteria included the following: (a) when there were different versions of the guidelines from the same health authority available, only the most recent one was included. (b) Editorials, commentaries, conference abstracts, and non-evidence-based narrative/personal reviews, manuscripts lacking of English version, were excluded.

Expert panel

Those who will be appointed by the core team. The participants should have the professional knowledge, training, and experience in the field of RA, with active participation in scientific research in this field, years of expertise of the involved experts ranged from 12 to 44 years.

Target audience

The guideline will be of particular interest to healthcare professionals who treat and manage patients with RA, mainly the rheumatologists. The guideline should also provide a helpful resource to general practitioners, physiotherapists, dieticians, and pharmacists as well as patients and those in the National Health Service who are in charge of commissioning the care for RA patients.


The Delphi technique is a well-established approach to gather expert-based verdicts to aiming at using them to identify a consensus. Its methodology is based on a series of several ‘rounds’ of questionnaires directed to experts committee [8].

Consensus process

Two Delphi rounds were completed to achieve consensus regarding the rheumatoid arthritis treat-to-target (T2T) management approach. In round 1, each participant was invited to rank 13 key clinical research questions. In round 2, the participants received individualized survey including 33 statements across forming the main items to consider in the T2T strategy of RA.

Voting process

Live voting was delivered in two online rounds limited within a pre-specified time. All the task force participants were asked to contribute and were pre-informed of the start-end times of each voting round. Every participant received a unique access link, and anonymous votes were collected and processed. Responses were evaluated and analysed independently. Comments raised by the participants on the different statements regarding its ‘re-phrasing, potential ambiguity, unidentified overlaps’ were gathered after each round and evaluated by the core team.


The members of the expert panel were asked to rate each statement in the range of 1–9 where 1 indicates ‘complete disagreement’ and 9 indicate ‘complete agreement’. Generally, responses can be stratified such as follows: 1–3: represent disagreement, 4–6: represent uncertainty, and 7–9: represent agreement. Voters were advised that it was not mandatory to vote on all statements, and that they may refrain from ranking any statement if it falls outside their area of speciality. An ‘uncertainty’ vote represents ‘inconvenience about the accuracy of the recommendation’. All statements were open for the entry of comments. The members were urged to leave comments, particularly wherever they vote a disagreement. Ranks of each item were recorded and mean and standard deviation calculated and entered anonymously into a database.

Definition of consensus

Before data analyses, it was determined that statements require 80% agreement in order to ignore or accept a statement. A total of 80% was selected as a proper cutoff point based on the study carried out by Lynn [11] who concluded that an 80% consensus reflect content validity of the statement. Achieving 80% agreement (scores 7–9) would, consequently, qualify the statements to become a recommendation in this guideline. Similarly, 80% disagreement (scores 1–3) means that this statement will be omitted [8,9,10]. If the rate came in the uncertainty score (4–6), this specific statement should be revised in view of the comments. If after the second round of votes, all votes on a statement fell into the agreement bracket (7–9), the levels of agreement on the statement of recommendation were defined as ‘high’ [12].

Developing the clinical care standards framework

Based on the outcomes of the Delphi process, a structured template was established to facilitate standardized identification of the variable treatment recommendation constituents. For each constituent, the format in which the recommendations/information to be delivered has been identified.

Chronogram of Delphi rounds

The first round took place between 20 and 24 November 2021 (5 days). The aspects identified as ignore or need amendment have been identified in view of the first Delphi round outcomes. Statements that needed reconsideration were revised in view of the participants’ comments and included in the second round. The second round took place on the 29th of November 2021 (5 days after the first round) and lasted for 8 days (until the 6th of December 2021).

Ethical aspects

This study was performed in accordance with the Helsinki Declaration. The Clinical, Evidence-based, Guidelines (CEG) initiative protocol was approved the local ethical committee: ethical approval code: 34842/8/21, ethical board Tanta University. Written ethics approval from the experts sharing in this work was deemed unnecessary according to national regulations.


Literature research and evidence selection

By using a search strategy, we identified 9895 possibly relevant studies during the research selection phase. A total of 9663 were excluded: 1068 duplicates and 8595 by title and abstract screening (studies did not examine population or intervention of interest, did not match study design of interest, or did not report outcome measures of interest). As a result, 232 studies were selected for full article evaluation. Due to the fact that 198 research did not provide evidence that matched the PICOT strategy, only 34 studies were considered in this study (Fig. 1). The level of evidence and grades of recommendations were mentioned in Table 1.

Fig. 1
figure 1

Flow chart for the systematic review process. PICOT, patient/population, intervention, comparison, outcomes, and time

Expert panel characteristics:

The Delphi form was sent to expert panel (n = 19), of whom 18 (94.7%) completed in the two rounds. The participants were from governorates and health centres throughout Egypt: Ain Shams University (n = 6, 33.33 %), Cairo University (n = 2, 11.11%), Tanta University (n = 2, 11.11%), Benha University (n = 2, 11.11%), Fayoum University (n = 1, 5.55%), Zagazig University (n = 1, 5.55%), Assiut University (n = 1, 5.55%), Minia University (n = 1, 5.55%), and Mansoura University (n = 1, 5.55%), in addition to (n = 1, 5.55%) international expert from the UK.

Table 2 showed general considerations and treat-to-target strategy for RA management, while Table 3 showed disease monitoring and remission parameters.

Table 2 Overarching principles and treat-to-target strategy
Table 3 Disease monitoring and remission parameters

Delphi round 1

This round was dedicated to the key clinical questions, which included 13 items (Table 4) including the following:

  • Overarching principles about RA diagnosis and assessment, disease remission, and low disease activity

  • How to monitor RA?

  • The target(s) of treatment (how to treat to target?)

  • Patient communication and shared decision-making, RA management, and drug tapering in RA management

  • How to personalize the patient care?

  • The non-pharmacological management in RA and the role of self-management in the treatment of RA

Table 4 Key clinical questions used to develop the guideline

The experts’ panel responded 94.7% (18/19) in round 1. The participant who did not share in round-1 Delphi was excluded from round 2. All domains and questions were agreed upon (with 80% of respondents strongly agreeing or agreeing), and no questions were retired.

Delphi round 2

Based on the literature research, a list of 33 recommended suggestions was generated using the input from round 1. The response rate for round 2 was 100% from the experts’ panel (18/18). Wording modifications were suggested for 9 statements. The statements were modified and amended. For all statements, the consensus was reached (as ≥ 80% of respondents strongly agreed or agreed).

Based on those results, this document was written, containing the answers to the key clinical questions which entail recommendations for the management of RA (Table 5).

Table 5 RA recommendations

Algorithm of these recommendations was demonstrated in Fig. 2; personalized care was demonstrated in Fig. 3.

Fig. 2
figure 2

Algorithm for TOT strategy in RA management

Fig. 3
figure 3

Personalized care

Types of DMARDs used are as follows:

Synthetic DMARDs

  • (csDMARDs): Conventional here implies that they have entered the treatment armament for RA in a conventional historic way that involved fortuitous and empiric findings of disease-modifying efficacy (e.g. methotrexate, leflunomide, sulfasalazine, hydroxychloroquine).

  • Targeted synthetic DMARDs: Chemical (oral) drugs that are developed by modelling them to interact with specific, well-defined molecules or known structures, particularly aiming to inhibit their active sites, e.g. baricitinib, tofacitinib, and upadacitinib.

Biological DMARDs: Drugs which made using biotechnology. They are genetically engineered to act like natural proteins in the immune system.

  • Biological originator DMARDs (TNFi: adalimumab, etanercept, certolizumab, golimumab, infliximab; IL-6Ri: tocilizumab, sarilumab; Costimulation-i: abatacept; anti-B cell (CD20): rituximab)

  • Biosimilar DMARDs(currently for: adalimumab, etanercept, infliximab, rituximab)

Communication, shared decision-making, self-management, and education

1. Explain the risks and benefits of treatment options to adults with RA in ways that can be easily understood. Throughout the course of their disease, offer them the opportunity to talk about and agree all aspects of their care and respect the decisions they make.

2. Implement shared decision-making in the management process. Offer verbal and written information to adults with RA as follows:

  • Improve their understanding of the condition and its management.

  • Counter any misconceptions they may have.

3. Adults with RA who wish to know more about their disease and its management should be offered the opportunity to take part in existing educational activities, including self-management programmes.


This updated guidelines for rheumatoid arthritis management include recommendations on referral, diagnosis, investigations, and treatment. It aims to improve quality of life and prevent joint damage by ensuring that people with rheumatoid arthritis receive the appropriate treatment protocols adopting a treat-to-target strategy. The guidelines summarize the current medical knowledge, weight the benefits and harms of diagnostic procedures and treatments, and give specific recommendations based on this information and on experts’ experience.

The developed guidelines are in general in agreement with the most recently published guidelines for the management of rheumatoid arthritis [13,14,15,16]. In addition to the quality presented, the developed guidelines not only addressed on the pharmacotherapy of rheumatoid arthritis but also consider the ‘non-pharmacologic’ approaches (such as quality of life, patient education, lifestyle advice, as well as self-management) offering a broad scope. This comes in contrast to the 2021-ACR [14] guidelines which focussed only on medication therapies to treat rheumatoid arthritis. The guidelines also endorse the use of short-term glucocorticoids when initiating or changing conventional DMARDs (this can be in the form of variable dose regimens and routes of administration). The steroid should not be used as long-term therapy but should be tapered and stopped as swiftly as clinically possible. This is in agreement with the EULAR guidelines [15] and in relative agreement with the ACR 2021 guidelines [14] which reported very low to moderate evidence assigned to the use of glucocorticoids, particularly for patients taking glucocorticoids to remain at target. Furthermore, this guidelines recommended that for those patients who do not achieve the target after taking the first conventional DMARD for 3 months, and in the absence of poor prognostic factors, the use of another conventional DMARDs, either as mono- or combination therapy, is advised rather than using biologic therapy. By 6 months of conventional DMARDs therapy, biologic therapy can be added for those patients whose disease activity is high or moderate and have poor prognostic factors.

Judgments about evidence and recommendations are complex; therefore, formulation of guidelines should be based on clear questions. Principally, any question addressing clinical management has four components: patients, an intervention, a comparison, and the outcomes of interest [17]. Grading the quality of evidence and the strength of recommendations is vital for this purpose. In this work, we implemented the Oxford Centre for Evidence-based Medicine (CEBM) system [7], which is in agreement with the EULAR guidelines for rheumatoid arthritis [15]. In contrast, the ACR adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) [18]. While the Oxford levels of evidence include 10 categories (Table 1), GRADE uses four levels for quality of evidence: high, moderate, low, and very low. These levels imply a gradient of confidence in estimates of treatment effect and thus a gradient in the consequent strength of inference [19]. While GRADE provides a systematic and transparent approach to assessing the certainty of evidence and strength of recommendations, it is important to acknowledge that using GRADE will commonly involve some subjective judgments, and assessments may vary between individuals [20, 21]. This is supported by the finding that inter-rater agreement for GRADE assessments by different, untrained individuals is limited [22, 23].

Guidelines help clinicians translate best evidence into best practice [24]. However, it is important to highlight that adherence to treatment recommendations will not guarantee a successful outcome in every patient in each clinical scenario. The ultimate assessment should be carried out by a rheumatologist responsible for the clinical decision-making and considering the individual patient medical status, priorities, favourite options, and values. Recommendations within this guideline are based on the best clinical evidence. Clinical practice guidelines aim to provide a frame on how to enhance the suitability and quality of care, to improve the interventions’ cost-effectiveness, to act as a tool for education, and to categorise relevant research pathways. Based on the level of evidence and strength of the recommendations, the recommendations are intended to help inform clinical decision-making [25]. This agrees with the outcomes of this work highlighted in the algorithm that there is no isolated target for the management of RA, but they are multiple pathways leading at the end to the desired goal.

In our work, we consider disease-sustained remission is the main goal for treating RA patients (clinical, ultrasonographic, and functional), while the EULAR 2019 updated recommendations [15] consider only clinical remission is the main therapeutic target for patients with RA. Also, we put clear cutoff point of starting biologic therapy. Also, we added clear and more detailed points on drug tapering, personalized medicine, and non-pharmacological management of RA.

The key strengths of this work are linked to the diversity as well as the experience of the contributors, the high levels of the achieved consensus, and the wide-ranging agreement with the most recently available management recommendations. Also, the methodology adopted the PICOT strategy, the patient-reported outcomes, and the treat-to-target outcome as the main foundations of this study.

Limitations of the guideline

One particular challenge with the current published guidelines is the limited comparative evidence to inform selection of therapies. Therefore, for the purpose of this work, indirect comparisons among trials/therapies were used. Though this guideline represents the best data available at the time of preparing this report, caution should be exercised in rendering the data; future studies may mandate alteration of the conclusions or recommendations included in this work. As health care is not universally uniform, it may be needed or even preferable to depart from the stated recommendations to set up a tailored management programme tailored to specific patients with particular circumstances. Just as adherence to guidelines may not constitute defence against a claim of negligence, so deviation from them should not necessarily be deemed negligent.

In conclusion, clinical guidelines have been upheld as an essential part of quality medical practice. This work was developed aiming at offering updated, concise, patient-focused, evidence-based, expert recommendations for the management of RA. As data continue to endorse best practices in management, implementation of this guideline in standard practice will ideally lead to improved quality of care for people with RA. The broad representation of the consensus panel would have a role in disseminating of the results of this work to such a large number of local rheumatologists, with consequent high chances of increased uptake and implementation of the guidelines.

The developed guidelines and recommendations are envisioned to offer general guidance for commonly met clinical scenarios. The recommendations do not command the care for individual patients. Adherence to the recommendations stated in this guideline should be considered as voluntary, with the ultimate decision to apply them to be decided by the treating healthcare professional in view of the specific patient’s individual condition and comorbidities. Guidelines and recommendations are projected to endorse useful or desirable outcomes but do not guarantee any specific outcome. The guidelines do not recommend any commercial products or services. The guidelines are meant to help in the decision-making process but do not convey all uncertainties of patient care.

Availability of data and materials

The data will be available upon reasonable request.



American College of Rheumatology


Biologic disease-modifying antirheumatic drugs


Bio-originator disease-modifying antirheumatic drugs


Biosimilar disease-modifying antirheumatic drugs


Conventional disease-modifying antirheumatic drugs


Centre for evidence-based medicine


The Clinical, Evidence-based, Guidelines


Disease activity score


Disease-modifying antirheumatic drugs


European Alliance of Associations for Rheumatology


Grading of Recommendations Assessment, Development and Evaluation


Health assessment questionnaire






Musculoskeletal ultrasound




Power Doppler ultrasound


Patient, intervention, comparison, outcome and time


Rheumatoid arthritis


Randomized controlled trial


Systematic review




Transcutaneous electrical nerve stimulators


Target synthetic disease-modifying antirheumatic drugs


Treat to target


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Author information

Authors and Affiliations



Conceptualization and design, YEM and MHA; acquisition of data, YEM and MHA; formal analysis, MEG; investigation, NG and MM; methodology, all authors; writing — original draft, YEM, MHA, and ST; final approval of the version to be submitted, all authors. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Mohammed Hassan Abu-Zaid.

Ethics declarations

Ethics approval and consent to participate

This study was performed in accordance with the Helsinki Declaration. This was a multistep process which followed the ‘Clinical, Evidence-based, Guidelines’ (CEG) initiative protocol (ethical approval code: 34842/8/21, ethical board Tanta University) aiming at setting up an actionable clinical gold standard for treat-to-target management of rheumatic and bone diseases.

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Not applicable

Competing interests

The authors declare that Mona Mansour is editor in chief. Mohammed Hassan Abu-Zaid, Salwa Galal, and Rehab Ali are associate editors in the Egyptian Rheumatology and Rehabilitation. Mohammed Mortada, Yasser El Miedany, Naglaa Gadallah, and Waleed Hassan are from editorial board of the journal. The other authors declare that they have no competing interests.

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El Miedany, Y., Abu-Zaid, M.H., El Gaafary, M. et al. Egyptian guidelines for the treatment of Rheumatoid Arthritis — 2022 update. Egypt Rheumatol Rehabil 49, 56 (2022).

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