Treatment with biological therapy is associated with faster recovery and lower frequency of treatment switch among rheumatic patients with Chikungunya fever

In our study, the use of bDMARD was associated with a shorter period of articular symptoms after Chikungunya fever infections as compared with patients using exclusively csDMARDs. However, we did not observe a statistically significant difference in the maximum severity of articular symptoms between these groups.Further we also did not observe a significant difference in the prevalence of positive IgG for CHIKV according to the use or not of biological agents, however seropositivity tended to be more prevalent among patients exclusively on csDMARDs (57.4%) comparing with patients on biologics (39.7%). It is possible that the use of bDMARDs may blunt the serologic response to CHIKV. Interestingly, we observed a higher prevalence of positive serology than previously reported in the general population (27%) and in rheumatic patients on treatment with biologics (25%) in the city of Recife in 2016–17 [9]. This observation may possibly reflect the now endemic nature of the disease, with more individuals becoming seropositive over time. As a matter of fact, the overall prevalence of seropositivity for CHIKV in our sample was numerically higher than that observed in the general healthy population in Reunion Islands (38.2%, 2005–6) [15], Ethiopia (43.6%, 2018) [16], and Zambia (36.9%, 2016) [17].

The CHIK symptoms are very typical and include fever and an intense and abrupt onset of joint pain [2], and cases occur generally in the context of an epidemiological outbreak. In the course of RA, ankylosing spondylitis (AS) and psoriatic arthritis (PsoA), disease flares are usually not accompanied by fever and joint symptoms usually occur in the same joints previously afflicted. In our study, CHIK-related symptoms were reported to affect joints unusually affected by the rheumatic disease (e.g., lumbar or dorsal pain was reported by 57.1% of RA patients). As in other studies [9, 10, 18], we did not find more severe symptoms or post-infectious complications of CHIK in patients using biological therapies. However, as our study is a survey of surviving patients, the results must be interpreted cautiously due to the possibility of selection bias.

There are few studies evaluating changes in articular symptoms caused by CHIKV infection in rheumatic patients using bDMARDs, although no previous study could adequately compare these patients with those exclusively on csDMARDs. Bautista-Vargas et al. followed 6 RA patients who had CHIK [18], 3 of them using a bDMARD (etanercept). No patient developed extra-articular manifestations, but all of them increased the usual dose of corticosteroids and 4 patients needed to switch or initiate biological therapy or jak inhibitor within 6 months due to worsening arthritis [18]. de Brito et al. (2016–17, Recife) also evaluated serology (IgG) for CHIKV in 186 patients with autoimmune inflammatory diseases (RA, AS or PsoA) on treatment with bDMARDs, and compared this group with 56 healthy people living in the same household as the patients [9]. There were 32 confirmed cases of CHIK (positive serology plus symptoms) among patients and 14 among controls. Persistence of musculoskeletal symptoms for more than 3 months post-CHIK occurred in 64% of controls and in only 28% of patients using bDMARDs (p = 0.021), especially anti-TNF agents [9]. Another study by Rosario et al. described 53 cases of CHIK in RA patients on biological therapy (monotherapy or in association with csDMARDs) [10]. In these patients, polyarthralgia occurred in 96.2% and arthritis was present in 47%; however, there was no difference in symptoms when this group was compared to patients with CHIK without concomitant rheumatic disease [10]. Patients were followed-up over 10 months and, during this period, therapy with csDMARD or bDMARD did not need to be modified in any patient and no complications occurred [10], corroborating data from our study on more favorable post-CHIK evolution in users of bDMARDs. In our study, articular symptoms during CHIKV infection were not significantly different in patients regardless of the use of bDMARDs. However, patients on biologics experienced faster recovery from joint symptoms and fewer treatment switches, even after stratification for possible confounding factors.

Although we found 16.5% of IgM positive serology for CHIKV in our sample (collected approximately one year after a reported CHIK fever episode), we found no association between positive IgM and longer duration of joint symptoms or any other symptom. Other studies have found similar results. A cohort study in Reunion Islands, evaluating healthy subjects after acute Chikungunya infection, demonstrated that 39.7% of the individuals maintained a positive result for IgM antibodies after 18 months with no association with persistent joint symptoms [19]. Other studies have also demonstrated persistence of positive serum IgM in 17% to 19% [20, 21] of healthy subjects for up to 12 months; however, the clinical relevance of this finding could not be determined.

Of note, this is the first study to compare the symptoms and clinical course of CHIK between rheumatic patients treated and not treated with biological therapy. The main limitation of our study is the retrospective design, possibly leading to recall bias, in which some participants might not have remembered some symptoms. On the other hand, all patients are prospectively followed up long before the CHIK outbreak and drug changes and serious adverse events are systematically monitored by the investigation center and the study's central coordination, limiting the possibility of bias. The number of confirmed cases of CHIKV infection (n = 32) was small, and our study may be underpowered for some analysis. Few patients received non-anti-TNF biologics, and so separate analysis according to class of bDMARD was not possible.

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