PET Scans Reveal Vascular Inflammation

Positron emission tomography (PET) provided objective evidence of response to treatment with tocilizumab (Actemra) in giant cell arteritis, according to a study by researchers from the National Institutes of Health.

In a cohort of 25 patients with active vasculitis, vascular inflammation was decreased over a median time of 1.1 years during treatment with tocilizumab using ¹⁸F-fluorodeoxyglucose (FDG) PET, reported Kaitlin A. Quinn, MD, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Maryland, and colleagues.

At baseline, the PET vascular activity score (PETVAS) was 24 on a scale of 0-27, with higher numbers reflecting greater inflammation and scores above 20 being considered active disease. PETVAS had declined to 18.5 at the most recent follow-up visit (P<0.01), the investigators noted in their study online in Rheumatology.

The observation suggested that FDG-PET could be incorporated into outcome measures for clinical trials in giant cell arteritis and could help guide individual management decisions, the team said. "FDG-PET could be employed to study treatment response in patients with active disease and potentially to assess relapse risk in patients in clinical remission."

Evaluation of disease activity in giant cell arteritis can be difficult, as symptoms such as headache are nonspecific and markers including acute phase reactants do not necessarily coordinate with disease activity, particularly in advanced disease. The mainstay of treatment in the past was glucocorticoids, but major clinical trials of tocilizumab demonstrated efficacy as a steroid-sparing treatment.

Those trials assessed response to treatment with clinical and laboratory measures, and did not include objective imaging findings. "Incorporating more objective measures such as vascular PET activity into clinical trial designs in large-vessel vasculitis may provide a more nuanced understanding of treatment of inflammation at the vascular level and may enable the conduct of more efficient trials that require smaller sample sizes to demonstrate drug efficacy," Quinn's group stated.

FDG-PET can reveal abnormal metabolic activity in arterial walls that is considered a surrogate for local inflammation. In this study, FDG-PET imaging was performed at baseline, before the initiation of tocilizumab treatment, and every 6 months thereafter. FDG uptake was assessed in four segments of the aorta and five branch arteries, and at each visit, clinical and laboratory variables also were evaluated.

The prospective National Institutes of Health giant cell arteritis cohort included 74 patients, 25 of whom were treated with tocilizumab.

Most of the patients were women, median age was 70.5, and median disease duration was 1.5 years. In 72% of patients, the active disease was a relapse, while in the remainder the disease was of new onset. Cranial symptoms were present in 36% of patients and constitutional symptoms in 52%.

Two-thirds of patients were on background prednisone, at a median daily dose of 6 mg. Methotrexate had previously been used in 56%, but was stopped before the initiation of tocilizumab.

To see if the effects of tocilizumab were independent of glucocorticoid use, the researchers also calculated PETVAS in 14 patients who were on low-dose prednisone (10 mg/day or less), with results that were similar to the main analysis. In these patients, there were reductions in the scores from 25 at baseline to 19 at last follow-up (P=0.04). There was no association between cumulative prednisone doses and changes in PETVAS, the researchers reported.

Twelve of the patients had follow-up of more than 18 months, and similar reductions to the first year of treatment were observed in the second year, the study showed.

Tocilizumab was discontinued in six patients -- five because of clinical remission and one because of persistent disease. At the time of discontinuation, the median PETVAS was 18.5, and a FDG-PET scan obtained 6 months after discontinuation showed worsening of vascular inflammation in five of the six patients, with a median PETVAS of 21.5. Two of the patients had a clinical relapse within the subsequent 6 months and were restarted on tocilizumab.

The optimal duration of treatment for giant cell arteritis with tocilizumab has not been determined. Randomized trials could be done to assess the risk of relapse utilizing PET scanning following treatment discontinuation, which "could provide much-needed data to guide management decisions in the later phases of giant cell arteritis," the authors wrote.

They also noted that almost half of patients in the study did have persistent vasculitis after a year's treatment with tocilizumab, which suggested that it alleviates the vascular inflammation, but does not completely resolve it. A possible explanation for this was that a longer duration of treatment may be needed in certain patients, the researchers said.

A limitation of the study, they noted, was its single-center design, with the possibility of referral bias.

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