A group was formed of 14 rheumatologists with expertise and publications in any of the following areas: axSpA, recommendations and therapeutic guidelines, clinical practice in the country’s various states and health systems. The executive committee (EC) comprised the principal investigators, the project coordinator and two spokespeople. Its functions were the planning and executing of the project, preparing the work agendas, and editing the recommendations. The systematic review of the literature (SLR) was carried out by two independent investigators.

The EC selected the expert team, themes and sub-themes related to the definition, concept and classification of SpA, demographic and clinical similarities or discrepancies compared to other populations, including their overall impact. It also developed the clinical and research questions using the ASAS/EULAR8 model, but not limited to it, to carry out the initial SLR.

The EC and independent investigators converted the clinical questions into research questions covering the following theme: inflammatory activity, structural deterioration, improvement, partial remission, inactive disease, moderate activity, high activity, very high activity, significant clinical improvement, very significant clinical improvement, quality of life and health status. In addition, they chose to retrieve information on the safety and efficacy of pharmacological, non-pharmacological and surgical treatments from studies after the SLR conducted for the ASAS/EULAR update in 2016.7

The literature search in the databases was conducted between January 2015 and March 2018, considering that most of the information prior to January 2015 had been obtained, analysed and published by ASAS/EULAR.7–9 Meta-analyses, systematic reviews, controlled and randomised clinical trials, controlled clinical trials and extension clinical trials identified in PubMed, Ovid-Medline, Cochrane Library, Scopus, Science Direct and CINAHL were chosen.

In accordance with the PICO (Patient or problem, Intervention, Comparison, Outcomes) structure, article eligibility was based on: 1) patients >18 years with diagnosis of SpA; 2) pharmacological therapeutic intervention with conventional synthetic or biological synthetic disease-modifying antirheumatic drugs (csDMARDs or bDMARDs, respectively), non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids and others, non-pharmacological (exercise and information programmes) and surgical; 3) comparison of interventions with different regimen or dose, placebo or none; 4) outcomes, including Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI), improvement criteria ASAS 20, ASAS 40, ASAS 5/6, ASAS-partial remission (PR), pain, C-reactive protein (CRP), radiographic indexes such as the Bath Ankylosing Spondylitis Radiology Index (BASRI), modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS), Radiographic Ankylosing Spondylitis Spinal Score (RASS), and MRI indices from the ASAS Task Force, Berlin and Leeds, and the Spondyloarthritis Research Consortium of Canada (SPARCC).10–18

The quality of evidence of the articles was assessed according to the Grading of Recommendations, Development and Evaluations (GRADE) document, based on risk of bias, consistency, direct results, heterogeneity, accuracy and publication bias, and the Oxford Centre for Evidence-Based Medicine’s (OCEBM) levels of evidence.19,20

In the first meeting, the experts presented the main characteristics and definitions in the management of SpAs to the plenary of the committee, discussed the circumstances and therapeutic options that exist in Mexico, and gave indications for the SLR based on different research questions.

In the second, the results of the SLR were reviewed and the 13 recommendations from the ASAS/EULAR update were followed in a structured way, discussing the current status of the evidence.7 The study coordinator presented each theme, sub-theme and recommendation to the plenary; she then gave the floor to each of the experts so that in less than 5 minutes they could give their reasons for voting for or against the proposal. The vote followed the Delphi technique in a positive or negative way according to the following levels (>80% in the first round, <75% in the second and <60% in the third). A priority order of recommendations was followed with adaptation to knowledge of the national context, experience of the experts and updated evidence.

We obtained 322 articles to review in depth (Fig. 1). Of these, 28 articles met the criteria to be included in the final review: 19 on pharmacological treatment (Appendix B supplementary material, Annex 1), 7 on non-pharmacological therapy and 2 on surgical approach (Appendix B supplementary material, Annex 2).

Fig. 1.

Flow chart. Systematic review to update the recommendations of the Mexican College of Rheumatology for the management of spondyloarthritis.

The ASAS/EULAR format includes 5 fundamental principles for the management of patients with SpA and 13 recommendations developed from them. Although this format is present in all the sets of recommendations developed by EULAR, our group preferred not to separate and to include the fundamental principles as part of the text of the recommendations because, although they deal with generic principles, we did not consider that there was much difference with respect to the individual recommendations.

The meaning of the updated questions and answers were discussed. The information concerning recommendations 1, 2, 3, 4, and 5 exceeded the capacity of the SLR and was not sufficient to change their meaning. On the other hand, we did not find substantial updated information relating to recommendations 6, 7, 8, 9, 10, 11, 12 and 13. Thus, the SLR that included the articles from the last 2 years did not result in important changes regarding the ASAS/EULAR 2016 recommendations.7 However, the Mexican group of experts made the recommendation, modification, change or substitution of some of the ASAS/EULAR recommendations clear in Table 1, which shows the 10 Mexican recommendations and the percentage of concordance.

In addition, through the analysis of the 10 recommendations, the information was stratified in the model known as palimpsest (Fig. 2).

Fig. 2.

“Palimpsest" style diagram of the Mexican recommendations for the management of spondyloarthritis resulting from the text of Table 1. The diagram is divided into two main parts, "General" and "Therapeutic modalities". The first relates to the fundamental principles; the second, to the therapeutic modalities.

Unlike the traditional flow chart in which the substitution of one therapeutic modality for another is a constant and therefore the changes are absolute and stepped - for example, the patient who did not improve with anti-inflammatory drugs switches to synthetic DMARDs; and if he/she does not improve with these either, they are replaced by biological DMARDs, going from one step to another - our diagram is based on aggregation and overlapping recalling the palimpsest style. With this model, therapeutic recommendations and changes are presented in a format close to clinical practice. In general, such a change involves adding and perhaps later substituting therapeutic modalities. For example, we do not substitute prednisone for sulfasalazine, nor this for etanercept before the loss of efficacy of the first and the certainty of the efficacy of the second have been demonstrated, but we add a new modality with greater efficacy to another already used in which the expected efficacy was not obtained. According to expert opinion, the proportion of patients who are treated with the drugs listed in recommendations 5 to 8 is much higher than the proportion who are treated with surgery. Also, the proportion receiving sulfasalazine is higher than the proportion receiving synthetic DMARDs. Although it seems contradictory, synthetic DMARDs do not reduce or stop the progressive worsening of the disease. With respect to biologics, the anti-inflammatory effect may be so great that the speed and deterioration in the structure of the joints and entheses is less. Recommendation 10 is of great importance since it refers to the access of the population with the disease to the most effective, safe, and remission-inducing treatments.

The themes relating to the profile of Mexican patients with SpA cover definition, concept and classification, demographic and clinical similarities, or discrepancies. In part, the purpose of this section was to investigate the characteristics of our population and structural and logistical aspects to determine whether there was compatibility with the therapeutic recommendations of the ASAS/EULAR group.

I. Definition, concept, and classification. The change in the definition and concept of the ASAS group was considered. AxSpA is the defining term for the entity characterized by acute and chronic inflammation in the synovial membrane and bone proliferation in the entheses of the sacroiliac, intervertebral, interapophyseal joints and peripheral sites.7,21,22 The predominant manifestations determine AxSpA21,23,24 or the peripheral form (p-SpA),25 alterations in the sacroiliac joints, in the radiographic, specifically AS,16,21,26 and non-radiographic (nr-SpA) varieties.21,23 The entities included in the SpA group continue independently, specifically PsA, reactive arthritis and arthritis associated with inflammatory bowel diseases and undifferentiated SpA. Changes in classification, specifically PsA, have not been accepted by all experts.27,28 In this paper, we adopt the classification of the ASAS group,23,25 we retain the nomenclature, definition and classification of SpAs made by the European Spondyloarthropathy Study Group (ESSG)29 and the definition of AS according to the modified New York criteria.26

II. Relevant socio-demographic and clinical manifestations: comparison with other populations. In our country, AxSpA occurs more frequently in males with the histocompatibility antigen HLA-B27 and aged around 30 years at the onset of symptoms.30–33 Among females, the clinical spectrum is broader and includes peripheral site involvement, overlap with fibromyalgia and less response to TNFi (tumour necrosis factor inhibitor). In comparison with European and Latin American populations, it has been observed that in the latter two, there is a higher prevalence of axial symptoms and lower in the peripheral sites, and greater age at the onset of symptoms.30–35 However, the group of experts considered that there are generally no important differences between the SpAs identified in the rest of the world.

III. Epidemiological impact. The prevalence of SpA in Mexico is .6% (95%CI: .4, .9); that of AxSpA is .3% (imaging studies approach) and .09% (HLA-B27 approach).36 The prevalence of AS is .1% (95%CI: .02, .2). AxSpAs are among the top 5 causes of care in specialist clinics.37 The prevalence of HLA-B27 in the general population and in healthy controls in association studies is 1%-4%.38,39

IV. Functional capacity, quality of life and health status. In a significant percentage, the effect of SpA on functional capacity, quality of life and health status is a burden affecting the patient and his/her environment. Studies, both inside and outside healthcare institutions, have reported that the cost of SpA is high when measured through out-of-pocket expenses and impoverishment, direct and indirect costs, and finally temporary and permanent disability. The health status of patients with AxSpA is lower compared to the general population (accepted for publication). More than half the patients with SpA in Mexico consider their health status to be poor.40,41

V. Survival and comorbidity. No precise information is available on survival. The most frequent concomitant diseases are osteoporosis, peptic acid disease and cardiovascular involvement.42,43 Although not exactly known, given the high prevalence of obesity and diabetes, in addition to the underdiagnosis of high blood pressure in Mexico, it is possible that there is a major prevalence of metabolic syndrome in Mexicans with SpA.44

VI. Access to high efficacy and high cost treatment. It is a fact that there is no therapeutic equity in our country. About 50% of the Mexican population has access to health systems with full coverage such as the Mexican Social Security Institute, the Institute of Security and Social Services for State Workers, Petróleos Mexicanos, the Ministry of National Defence, prepaid systems to banks and other organisations and systems with state and municipal coverage. However, the other half of the population does not have a medical service to cover the cost of these types of diseases. For these people, there is the popular insurance and the Ministry of Health which do not have the capacity to pay for chronic disease such as SpA and many others. The cost of this type of treatment is borne by the patient and their family; in the case of rheumatoid arthritis and possibly SpA, the higher the percentage of out-of-pocket expenditure in families, the greater their impoverishment.39,40,45