Disclosures: The researchers report funding from F. Hoffmann-La Roche. Unizony reports research funding from Roche/Genentech. Please see the study for all other authors’ relevant financial disclosures.
June 30, 2021
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Tocilizumab plus prednisone reduces treatment failure risk sixfold in giant cell arteritis

Disclosures: The researchers report funding from F. Hoffmann-La Roche. Unizony reports research funding from Roche/Genentech. Please see the study for all other authors’ relevant financial disclosures.
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Tocilizumab plus prednisone was linked to a sixfold reduced risk for treatment failure in patients with giant cell arteritis, with highest risks reported among women and patients treated with prednisone monotherapy, according to data.

Additionally, the researchers concluded that lower starting prednisone doses and impaired patient-reported outcomes are linked with failure to respond to tocilizumab (Actemra, Genentech).

Prednisone monotherapy and female sex are the strongest risk factors for treatment failure in patients with GCA, according to data derived from Unizony SH, et al. Arthritis Rheumatol. 2021;doi:10.1136/annrheumdis-2021-220347.

“Several studies have explored factors associated with disease relapse in patients with GCA treated only with glucocorticoids,” Sebastian H. Unizony, MD, of Massachusetts General Hospital, in Boston, and colleagues wrote in the Annals of the Rheumatic Diseases. “Identified predictors for treatment failure have included sex, clinical features at disease onset (eg, polymyalgia rheumatica [PMR] symptoms, strong systemic inflammatory response and weight loss), certain comorbidities (eg, diabetes) and increased serum proinflammatory cytokine levels (interleukin-6 and TNF-).

“However, a consistent phenotype associated with treatment failure has not been identified, and results found in some studies have not always been replicated in others,” they added. “In contrast, virtually nothing is known about determinants for disease relapse in patients treated with tocilizumab. This problem, coupled with the unreliability of C-reactive protein levels and the erythrocyte sedimentation rate (ESR) for disease activity monitoring with IL-6 blockade therapy, makes the longitudinal care of patients with GCA treated with tocilizumab challenging.”

To determine the predictors of treatment failure among patients with GCA receiving glucocorticoids, either alone or in combination with tocilizumab, Unizony and colleagues conducted a post hoc analysis of the Giant-Cell Arteritis Actemra (GiACTA) trial. In this trial, participants with active disease across 76 centers in 14 countries were randomized 2:1:1:1 to receive either 162mg of subcutaneous tocilizumab every week plus a 26-week prednisone taper, tocilizumab 162mg every other week plus a 26-week prednisone taper, placebo plus a 26-week prednisone taper, or placebo plus a 52-week prednisone taper.

In all, the intention-to-treat population included 250 participants. For their own analysis, Unizony and colleagues combined the two tocilizumab-plus-prednisone groups, as well as the two placebo-plus-prednisone arms, for a total of two groups with 149 and 101 participants, respectively. They defined responders as those who maintained remission through week 52, while treatment failure was defined as an inability to achieve remission by week 12 or relapse between weeks 12 and 52.

The researchers used univariate and multivariable analyses to assess patient characteristics, disease-related and treatment-related factors and patient-reported outcomes as potential predictors.

According to the researchers, after adjusting for confounders, treatment failure was significantly less likely in the tocilizumab-plus-prednisone group compared with the placebo-plus-prednisone arm (OR = 0.2; 95%CI, 0.1-0.3). Meanwhile, the risk for treatment failure was significantly higher among women compared with men in the placebo-plus-prednisone group (OR = 5.2; 95%CI, 1.6-17.2) but not in the tocilizumab-plus-prednisone group. Predictors of treatment failure in the tocilizumab-plus-prednisone group included lower baseline prednisone doses and worse patient-reported outcomes at baseline.

“Our analysis identified independent predictors of treatment failure in GCA,” Unizony and colleagues wrote. “These include the use of glucocorticoid monotherapy in general. In addition, a sharp disparity between women and men was observed among patients treated with prednisone alone: women had a strikingly higher risk for treatment failure, reflected by an OR of 5.2. Among patients randomly assigned to tocilizumab-based regimens, lower initial prednisone doses and worse PROs were significant predictors of treatment failure.”