One in five patients experiences new symptom domains, highlighting the need for comprehensive monitoring
in patients with giant cell arteritis, highlighting that relapse often differs from initial presentation and may involve new symptom domains.
Findings have been published this month in Seminars in Arthritis and Rheumatism.
GCA is the most common primary vasculitis in people aged over 50 years and primarily affects the aorta and its major branches.
Patients typically present with headache and polymyalgia rheumatica, which causes muscle pain and stiffness, but the disease can also manifest with a variety of other symptoms such as scalp tenderness, transient or permanent vision loss, fever of unknown origin, stroke, or pain in the jaw, tongue or limbs due to reduced blood flow.
Research has identified different clinical patterns of GCA, including cranial-dominant, which mainly affects the arteries in the head; large-vessel dominant, which primarily involves the aorta and its branches; and mixed cranial-large-vessel, which displays features of both.
These patterns help explain the wide variation in symptoms observed at the time of diagnosis.
“Relapse in GCA is common with 50 to 75 % of patients having at least one relapse during the course of disease while receiving glucocorticoid (GCs) monotherapy, the historical mainstay of treatment,” the authors wrote.
“Tocilizumab (TCZ), an inhibitor of the soluble and membrane-bound interleukin 6 receptors, is currently the only approved medication for treatment of new and relapsing GCA and has demonstrated GC-sparing effects as well as reduction in risk of relapse.
“However, relapses still occur in 14–28 % of patients on TCZ and in 42–58 % following discontinuation.”
The latest analysis, which included 510 patients across three established cohorts treated either with glucocorticoids alone or with tocilizumab, followed individuals for a median of more than five years to assess concordance of symptoms at diagnosis, first relapse, and second relapse.
Relapse in GCA was common: two-thirds of patients experienced at least one relapse within five years, and more than a third had two or more.
At diagnosis, most patients presented with multiple symptom domains, including cranial, musculoskeletal, constitutional, visual or large vessel involvement. In contrast, at relapse, symptoms tended to be confined to a single category, most commonly musculoskeletal or cranial.
Importantly, about one in five patients relapsed with a symptom domain that had not been present at diagnosis, underscoring the heterogeneity of disease expression over time.
The strongest concordance was observed between symptoms at first and second relapse, suggesting that recent disease activity may be a better predictor of subsequent relapse than initial presentation.
For example, patients with musculoskeletal or cranial symptoms at first relapse had a high likelihood of repeating those symptoms at second relapse. By contrast, the predictive value of baseline presentation was lower, particularly for visual and large vessel involvement, although baseline features did influence subsequent risk.
Patients with visual or large vessel symptoms at diagnosis were significantly more likely to experience these manifestations again at relapse, while absence of cranial symptoms at baseline was associated with a near-zero probability of visual relapse.
The study also provided important observations regarding treatment. While tocilizumab was associated with fewer relapses overall compared to glucocorticoid-only cohorts, relapses still occurred, most often with musculoskeletal or cranial symptoms.
Constitutional features were relatively uncommon during relapse, suggesting clinicians should consider alternative diagnoses, such as infection, when they arise in patients on biologic therapy.
The authors said this study was “largest single-enterprise patient-level concordance analysis evaluating baseline features and relapse symptoms in GCA to date”.
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“In addition, this is the first study to explore both first and second relapse concordance and to evaluate cohorts of patients treated with or without tocilizumab,” they said.
They said their findings had direct implications for patient education and clinical monitoring.
“Although the majority of patients will have a symptom at relapse concordant with baseline presentation, still one out of five patients in our study had a symptom domain at relapse not observed at diagnosis,” they wrote.
“The only other study to date evaluating baseline to first relapse concordance has also shown evidence that patients with GCA do not necessarily have the same symptoms at diagnosis as at relapse.
“For example, Moreel and colleagues noted [in the journal Rheumatology] that while isolated PMR accounted for only 10% of patients at GCA diagnosis, it was the most common category seen at first relapse (46%).
“Taken together, our data and that of Moreel et al., underscore the importance of educating both providers and patients on the breadth of GCA-associated symptoms so that they can appropriately and timely recognize symptoms that are consistent with relapse, even if such symptoms were not part of their initial presentation.”
The researchers did note limitations of the study, including its retrospective nature and the symptom data relied on electronic medical record documentation.
“Second, regarding visual symptoms, both transitory and permanent visual symptoms were pooled equally, and therefore do not differentiate real-life differences in severity. Third, the percentage of patients with LV imaging at baseline and/or relapse varied across cohorts with the highest imaging among the biopsy-negative cohort (C2) and the lowest among the historic biopsy-proven cohort (C1),” they wrote.
“The lower frequency of imaging in C1 is most likely due to the timing of diagnosis (1998–2013) in this cohort which predated the consensus recommendation of baseline non-invasive imaging to evaluate for presence of LV involvement.”
Since imaging was not standardised, the probability of LV at relapse may be over or under-estimated and future studies utilising systematically obtained imaging among patients with GCA were needed, the authors said.
“Finally, this data originates from a tertiary care centre which may include a higher proportion of patients with severe disease, so the relapse rates may not reflect the overall population of patients with GCA,” they wrote.
However, they did highlight the study strengths, including the individual evaluation of both prednisone without biologic therapy, the historic standard of treatment, as well as those on tocilizumab, now the current standard of care. In addition, the combined cohort represented the largest single-enterprise cohort of patients with GCA with focus on relapse and the first to evaluate baseline, first and second relapse concordance.
“In conclusion, our data provides valuable information and guidance on outlining the probability and risk of relapse symptoms based on the presence or absence of these features at baseline or first relapse,” they concluded.
“At diagnosis, patients present more often with multiple domains of symptoms but more frequently have a single domain at relapse.
“Patients and clinicians should be educated on the breadth of GCA symptoms because 20% of first relapses are in a domain not previously experienced at diagnosis. Further studies evaluating concordance are needed to ensure these findings are replicable.”
