Depression in spondyloarthritis: can we kill two birds with one stone?

Spondyloarthropathies (SpA) encompass many different forms of inflammatory arthritis (including PsA), affecting the spine (axial SpA [axSpA]) and/or peripheral joints (peripheral SpA). The sites that are primarily affected in SpA are the sacroiliac joints, spine, peripheral joints, tendons and entheses. However, specific extra-articular manifestations like uveitis, psoriasis and inflammatory bowel disease are commonly observed in these patients [1]. Of note, people living with SpA may additionally exhibit comorbidities, the most well-recognized of which are cardiovascular disease and mental health disorders. Prompt identification and treatment of these conditions is of importance as they contribute to the patient’s overall disease burden and affect therapeutic outcomes [2].

Ideally, treatment of the index disease should also be beneficial for comorbidities as well. Although this has been well established for biologic (b)DMARDs and CVD, especially in other forms of inflammatory arthritis like rheumatoid arthritis [3], this is unclear for mental health disorders in the setting of SpA.

Along these lines, Webers et al. [4], analysed data from a cross-sectional international observational study (ASAS HI Validation Study) to examine the impact of therapeutic regimes used in SpA on depressive symptoms and determine whether this impact varies between different drugs. Patients were evaluated both before and after (follow-up visit) commencing treatment with NSAIDs, conventional synthetic (cs)DMARDs and TNF inhibitors (TNFi). The Hospital Anxiety and Depression Scale (depression-subscale—HADS-D, 0–21) was used to measure depressive symptoms. On this scale, higher scores indicate depressive symptomatology, while HADS-D ≥ 8 and HADS-D ≥ 11 designate ‘possible’ and ‘probable’ depression, respectively. The population of this study comprised 304 individuals with axial or peripheral SpA (n = 260, 85% and n = 44, 15%, respectively) who started NSAIDs, csDMARDs or TNFi (n = 102, 45 and 157, respectively).

Depressive symptomatology was significantly improved in all groups at the follow-up visit. Patients treated with TNFi vs those who received NSAIDs displayed a greater improvement in their HADS-D scores and reduced odds of having ‘possible depression’ at follow-up, after adjusting for age, gender and HLA-B27 status. This difference was largely attenuated after adjustments for disease activity (ASDAS, BASDAI) but not when CRP was tested as a confounder. Of note, results for ‘probable depression’ were largely similar but number of patients in this category was too low to lead to robust conclusions.

This is the first longitudinal, prospective study reporting that TNFi in SpA are indeed helpful for alleviating depressive symptomatology. This was found to be associated with improvements in disease activity. Interestingly, changes in CRP did not appear to play a fundamental role. The above-mentioned findings should be seen in light of some limitations of this study. First, axSpA and peripheral SpA patients are analysed as one group with the number of patients enrolled being relatively small for the latter. As the authors state, though, pre-planned analyses by SpA subtype showed similar results (at least for axSpA). Second, treatment only with TNFi and not with other bDMARDs (e.g. anti-IL-17 reagents) or Janus kinase inhibitors was examined. Finally, anxiety which is less investigated in SpA, was not evaluated. Future studies designed for this purpose are expected to address these issues.

It is gradually becoming clearer that compared with the general population, people living with SpA display increased frequency of symptomatology related to mental health. This mainly pertains to depression, which is an established comorbidity for both axSpA and PsA [5], while anxiety is far less studied. In addition to impairing daily activities and quality of life, these comorbidities also mitigate therapeutic effects [6, 7]. Furthermore, as it has been shown for PsA, depression might also significantly affect patient-reported outcomes, possibly acting as a confounder for therapeutic responses [7].

In RA the link between inflammation and depression is better described [8]; in contrast, in SpA the link is still elusive. Besides, CRP is not elevated in many patients with PsA despite active disease [7, 9], implying that other inflammatory pathways operate. This is in agreement with the findings of Webers et al. [4].

It is worth mentioning that in clinical practice—but also in clinical trials—there are several challenges in assessing and reporting these comorbidities. First, there are many different tools, some of which are not well validated. Second, concurring fibromyalgia [7] and/or fatigue can distort patient-reported outcomes related to mental health. Finally, it is a field of debate whether conditions thought of as comorbidities could better fit under the term ‘co-existing clinical conditions’ or even ‘extra-articular manifestations’ suggesting thus a pathophysiological connection with the index disease [10].

In the era of ‘shared decision making’ and ‘personalized medicine’, a tailored therapeutic approach is expected for healthcare professionals in rheumatology. Given that the many of the drugs in the rheumatologist’s arsenal have comparable efficacy and safety for key aspects of a disease (e.g. arthritis), other parameters like patients’ preferences and co-morbidities will finally define the therapeutic choice.

Webers et al. showed that TNFi can be beneficial for both depressive symptomatology and inflammatory arthritis. Future studies are warranted to show whether this effect could be more pronounced for some of the bDMARDs or targeted synthetic DMARDs.

Data availability

No new data were generated or analyzed in support of this article.

Funding

No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article.

Disclosure statement: G.E.F. has received honoraria/speaker fees from Abbvie, Aenorasis, Novartis, Lilly, Jannssen, Amgen and Pfizer.

References