Tocilizumab An IL-6 inhibitor. Promising Treatment for Giant Cell Arteritis?

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From Medscape Prof Jonathan Kay Professor of medicine at the University of Massachusetts Medical School.

Tocilizumab, an interleukin (IL)-6 receptor inhibitor in giant cell arteritis. This study was an efficacy and safety study looking at tocilizumab in patients with documented giant cell arteritis to see whether tocilizumab improved the remission of patients after tapering from glucocorticoid therapy. The patients were studied for 52 weeks, and patients who were at least 50 years of age who had giant cell arteritis confirmed by temporal artery biopsy or cross-sectional imaging with elevation of acute-phase reactants that was attributable to giant cell arteritis were randomly assigned 1:1:2:1 into four groups.

The first group was treated with a short course of prednisone over 26 weeks, which was tapered, and they were given a weekly subcutaneous placebo. The second group received a long course of prednisone tapered over 52 weeks, again, with a weekly subcutaneous placebo. The third group received weekly subcutaneous tocilizumab at the usual dose of 162 mg and a 26-week short-course prednisone taper. The fourth group received an every-other-week dose of tocilizumab subcutaneously at 162 mg and a short-course prednisone taper over 26 weeks. The randomization allowed twice as many patients to be entered into the weekly subcutaneous tocilizumab arm as into the other three arms.

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Anti‑citrullinated peptide antibodies and their value for predicting responses to biologic agents: a review

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Rheumatol Int DOI 10.1007/s00296-016-3506-3

Emilio Martin‑Mola1,7 · Alejandro Balsa1 · Rosario García‑Vicuna2 · Juan Gómez‑Reino3 · Miguel Angel González‑Gay4 · Raimon Sanmartí5 · Estíbaliz Loza

Abstract Anti-citrullinated peptide antibodies (ACPAs) play an important pathogenic role both at the onset and during the disease course. These antibodies precede the clinical appearance of rheumatoid arthritis (RA) and are associated with a less favorable prognosis, both clinically and radiologically. The objective of this work was to conduct a comprehensive review of studies published through September 2015 of ACPAs’ role as a predictor of the therapeutic response to the biological agents in RA patients. The review also includes summary of the biology and detection of ACPAs as well as ACPAs in relation to joint disease and CV disease and the possible role of seroconversion. The reviews of studies examining TNF inhibitors and tocilizumab yielded negative results. In the case of rituximab, the data indicated a greater probability of clinical benefit in ACPA+ patients versus ACPA− patients, as has been previously described for rheumatoid factor. Nonetheless, the effect is discreet and heterogeneous. Another drug that may have greater effectiveness in ACPA+ patients is abatacept. Some studies have suggested that the drug is more efficient in ACPA+ patients and that those patients show greater drug retention. In a subanalysis of the AMPLE trial, patients with very high ACPA titers who were treated with abatacept had a statistically significant response compared to patients with lower titers. In summary, the available studies suggest that the presence of or high titers of ACPA may predict a better response to rituximab and/or abatacept. Evidence regarding TNFi and tocilizumab is lacking. However, there is a lack of studies with appropriate designs to demonstrate that some drugs are superior to others for ACPA+ patients.

Similar RA Outcomes with Abatacept & Tocilizumab

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The Rheumatologist

August 17, 2015 • By Will Boggs, MD

NEW YORK (Reuters Health)—Clinical outcomes of rheumatoid arthritis (RA) are similar with abatacept and tocilizumab treatment, but the factors that predict efficacy differ for the two agents.

Abatacept targets T cells, whereas tocilizumab targets interleukin-6, and both are used in patients whose disease has proven refractory to methotrexate.

Dr. Tanaka’s team used a propensity score-matched analysis to compare clinical outcomes of abatacept and tocilizumab treatment of 102 patients in each group and sought to determine the predictive factors of the efficacy of each treatment.

Retention rates at 52 weeks were similar for abatacept (71.6%) and tocilizumab (68.6%). Discontinuation for inadequate effect was more common with abatacept (22.5%) than with tocilizumab (16.7%), according to the Aug. 5 online report in Annals of the Rheumatic Diseases.

Patients experienced similar improvements in Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire Disability Index (HAQ-DI), and Clinical Disease Activity Index (CDAI) with abatacept and tocilizumab treatment.

In contrast, the improvement in DAS28-ESR (the 28-joint count disease activity score-erythrocyte sedimentation rate) was greater with tocilizumab than with abatacept.

Lower baseline SDAI and higher baseline rheumatoid factor titer predicted better CDAI outcomes of abatacept treatment, whereas previous use of a biological agent and lower baseline HAQ-DI score predicted better tocilizumab outcomes.

“These factors should be considered when choosing one of these drugs,” Dr. Tanaka said. “Thus, this report may contribute (to) progress in ‘precision medicine’ in the field of RA.”