The prevalence of peripheral arthritis in axSpA has been reported in different cohorts. However, this is one of the first studies to provide data regarding the natural history of this clinical feature in daily practice. We found that new first episodes of arthritis still appeared over time since the prevalence increased from 21.3% at baseline to 36.0% after 5 years, with a person-time rate of 3.7 new cases per 100 person-years. This last percentage is similar to those reported in non-recent axSpA cohorts [6, 7], suggesting a relationship between the prevalence and the disease duration. Similar results have been recently published concerning peripheral enthesitis in the DESIR cohort, in which the prevalence of this symptom increased from 55.8 to 71% after 5 years of follow-up [19]. This increasing number of new first episode of peripheral arthritis over time is also confirmed by the fact that 65.9% of patients showed the first episode after axial involvement, suggesting that arthritis can appear at any time during the disease. However, we are aware that the low prevalence of peripheral arthritis before axial symptoms (20.4%) could be influenced by “recall bias”, and the higher prevalence of arthritis after axial involvement can be associated with a systematic physical examination by the rheumatologist at every study visit. These data confirm the high probability of occurrence of peripheral arthritis over time after the one of axial symptoms, emphasizing the importance of a systematic iterative check of peripheral manifestations during the monitoring of these patients. Interestingly, 47% of patients showed this first episode after axSpA diagnosis, which means that the information of a past history or current peripheral arthritis might facilitate the diagnosis.
We found that the development of this clinical feature was more common among older patients, confirming the greater prevalence of peripheral arthritis over time. Interestingly, we did not found an independent association with either IBD or psoriasis. The high prevalence of peripheral arthritis in PsA is well known [20]; however, here we observed that in axSpA, this association may not be as evident. Our results showed that the presence of arthritis was also associated with the development of other peripheral symptoms, which are in line with those reported in the ESPeranza cohort, in which dactylitis, arthritis and enthesitis were closely interrelated [21]. Interestingly, we found an inverse association between any concomitant arthritis and (a) HLA-B27 positivity, (b) presence of uveitis and (c) tobacco use. All these associated factors are in the opposite direction than the ones reported in patients with a pure axial disease (e.g. B27 positivity, uveitis and smoking habits) [22], suggesting a different physio pathological pathway. In addition, the relatively low prevalence of MRI or X-ray sacroiliitis could indicate that part of these patients has predominant peripheral disease instead of axial disease. However, all patients in the DESIR cohort have suffered from IBP suggestive of axSpA at any time, which leads to their classification as axSpA. An inverse association between smoking and peripheral arthritis in SpA patients has been previously reported [23, 24]. A recent study also suggested the “smoking paradox” in PsA, which described that smoking increased risk of PsA in the general population but appeared protective among psoriatic patients [25]. In this study, authors raised a possible bias by uncontrolled confounding. Regarding our results, we wondered whether non-smoking and peripheral arthritis are biologically or statistically associated, so further studies are needed to evaluate this association.
Concerning drug intake, we found that patients with arthritis had a greater use of csDMARDs and glucocorticoids. These results are not surprising since in accordance to the current ASAS-EULAR recommendations, glucocorticoids injections and sulfasalazine may be considered in case of peripheral arthritis [26]. However, it is interesting that, in our study, patients with arthritis showed a greater use of bDMARDs but similar use of NSAIDs compared to that of patients without arthritis. One may speculate that NSAIDs would control the axial symptoms in both groups, but the presence of arthritis could increase the likelihood of starting a TNFb because of the higher disease activity and the negative impact of peripheral arthritis on PROs. In fact, a previous study in the DESIR cohort has demonstrated that the Ankylosing Spondylitis Disease Activity Score (ASDAS) and the presence of synovitis act as independent factors associated with TNFb initiation [27].
Indeed, here, we demonstrated that patients who have ever suffered from peripheral arthritis at any time during the 5 years of follow-up period showed poorer quality of life and increased days of sick leave over time. Despite the evaluation of the clinical relevance of these results is more difficult, the fact that 36.9% of patients without arthritis and 50.2% with arthritis showed an active disease (BASDAI > 40) demonstrates the importance of this feature.
One limitation of this study is the difficulty of precisely evaluating arthritis that occurred before the inclusion visit and between two study visits because of the absence of physical examination in these time points. However, we have taken into account patients who received corticosteroid intraarticular injections between two visits to be considered as patients with arthritis. Another limitation is that we could not definitively rule out the possibility of a concomitant osteoarthritis in certain patients, partly because intra-articular injections could be performed for this diagnosis in some cases. The main strength is that this report is one of the few non-RCT studies that evaluate this feature over time.