Profile and course of early rheumatoid arthritis in Morocco: a two-year follow-up study

Rheumatoid arthritis (RA) is the most common inflammatory chronic disease of the joints. It is characterized by disease activity and bone destruction resulting in joint destruction, functional impairment, and increased mortality [1–3]. In Morocco, RA has a major socioeconomic impact [4]. The low socioeconomic status of many patients and the inadequate social welfare and health insurance systems contribute to weight of this burden [4].

Early recognition of RA and intervention appear to be keys to optimal management of this chronic disabling disease [5]. There is a lack of research on early RA in Morocco. The purpose of this study is to establish the profile and the course of an early RA cohort between baseline and 2 years later. We would like also to determine in this prospective study if there are any possible predictor factors of structural progression.

This prospective study constitutes a real-life design and provides, for the first time in Morocco and to our knowledge in Africa, the profile of early RA in a developing African country. It shows also that there are no predictor factors of radiographic progression after 2 years of follow-up.

The age onset of RA in Morocco has been reported in a previous retrospective study to be lower than in western countries [13]. In the same way, recent data on the profile of patients with RA in 8 clinics in North Africa (Morocco and Egypt) in the QUEST-RA (Quantitative Standard Monitoring of Patients with RA) database, shows that patients in North Africa are younger than patients in other countries [14]. Then, our findings of similarity of with RA age onset in western countries should be taken with caution and may not be extended to the Moroccan population.

The optimal approach to early RA management requires early referral of patients with arthritis to specialists and early diagnosis of the disease using mainly clinical and serological investigations [15]. In our study population, referral to specialists was delayed since it took nearly 20 weeks. Therefore, more awareness of the generalists is required to promote early referral to a specialist in order to guarantee the patient's early diagnosis and therapeutic intervention. This early diagnosis challenge remains greater for developing countries where RA management is still not considered as a public health priority even if it constitutes an enormous socioeconomic burden [4, 16].

ACPA has acquired for many years a great interest in early RA diagnosis. It's to be noted that our ACPA percentage result was similar to that reported by Meyer and al in their cohort [17]. Regarding the genetic concern, association with Human Leukocyte Antigen (HLA)-DRB alleles, implicated in the aetiopathogenesis of Rheumatoid Arthritis (RA), is found to be different in various ethnic groups [18]. In the Moroccan population, there is only one study which focused on evaluating the distribution of class I and class II HLA genes. In this controlled data, Atouf et al suggest that DRB1*04 predisposes to RA in the Moroccan population [19].

At the 2 year assessment, 6 patients (13.6%) have stopped the DMARD due to socioeconomic difficulties. Our finding highlights once more another frequent problem in developing countries inherent to socioeconomic difficulties encountered in chronic diseases management [16]. Rkain et al reported that 62% of Moroccan patients with established RA reported bad observance to treatments because of financial difficulties [4]. In the same way, an earlier data on therapeutic maintenance of MTX in RA reported that 14% of Moroccan patients stopped MTX for socioeconomic reasons [20].

The significant improvement of the disease status including clinical and biologic parameters is in concordance with the literature findings [21, 22].

Practically a third of patients were in remission after this period whereas there were no patients at baseline. Remission rates range from 3% to 68% [23] in RA studies depending on selection of remission criteria, patient selection, duration of the follow-up period, and therapies.

Our study has provided large information on structural progression. Forty patients (27.5%) had at least one erosion at baseline. Previous studies have widely demonstrated that joint damage in RA occurs early in the disease process [24]. Patients with duration of symptoms less than 3 months may have already evidence of destruction [25]. In the ESPOIR cohort, 20% of 813 patients with mean disease duration of 107 days had hand or foot erosions [26].

Two thirds of our patients did not show any significant radiographic progression after 2 years of follow-up.

Comparison of this result with literature is difficult because of the differences in the study design, patients and disease features.

Both nonprogressor and progressor patients showed significant improvement of clinical and biologic baseline parameters. Those findings are in line with previous data showing that radiological progression occurs despite a clinically and biologically acceptable disease control [27, 28].

Traditional therapy with a single DMARD is often insufficient to prevent a poor long-term outcome of rheumatoid arthritis (RA) [29]. Trials in RA patients have shown that treatment with combination therapy and/or biologic agents is more effective in preventing radiographic joint damage than MTX as monotheray [29–31]. Our progressor patients would probably benefit strongly from DMARD combinations or biologic agents.

Many predictor factors of structural progression were reported in literature [32–35]. According to most of the published reports, long-term progression of joint damage was best predicted at baseline by the presence of IgM or IgA rheumatoid factor, high ESR or CRP level, number of swollen joints, presence of anti-CCP antibodies, HLA-DRB1*0401 and 0404 genes, HAQ and early radiographic erosions. In our study, univariate analysis has initially shown that the radiographic progression was significantly associated with three baseline factors: swollen joint count, total SVDH and Joint space narrowing scores. However, none of those factors have been retained as being independent factors of radiologic progression after multiple logistic regression. This observed lack of association between radiographic progression and different factors shown in literature could be due to a lack of power.

Many limitations should be recognized in our study. First, we recognize that choosing the ACR 1987 classification criteria for RA to recruit patients may be criticized and could be a bias recruitment, possibly misjudging the baseline structural damage. But at our study onset, a few years ago, Early arthritis was "ill-defined": in some studies a disease duration of up to three years was accepted, whereas other protocols required a much shorter maximum duration of symptoms [36]. In addition, because of technical and financial considerations, we have not included in the design study regular assessment throughout the 2 years of follow-up. Thus, we were unable to calculate the score of radiographic progression. Finally, we should perhaps have included in database more details on socioeconomic conditions to analyze their possible contribution to the course of the disease in our context.

More than a research subject, this study gave us as clinicians the opportunity to find out the early RA profile in the Moroccan context.

This study reports, for the first time in Morocco, a developing African country, a large amount of information concerning the profile and the course of early RA.

Patients, receiving, for most of them, Methotrexate in monotherapy and low doses of corticosteroids, showed an improvement of all clinical and biological disease parameters. Moreover, remission was obtained in one third of patients and two thirds of the cohort had no radiographic progression at 2 years. No predictor factors of radiographic progression were found out probably in relation with the small number of patients.

The findings of this study also highlight the difficulties of early RA in developing countries. The delay in referral to specialists and interruption of DMARD due to financial difficulties are the most important problems encountered in our context.

The small size of our sample and the absence of regular monitoring of clinical, biological and radiographical parameters during the course of the disease are the most important limitations of our study.

The best way to investigate the course of early RA in the Moroccan population would be through a prospective longitudinal study, following an unbiased cohort of patients with early RA with regular clinical, biological and radiographical assessments for many years. Such multicentric inception cohort of early arthritis with a larger sample will give more precious informations about early RA characteristics and course and will constitute a major keystone in the management of this disabling disease in our country. Such a prospective study is already ongoing in Morocco.