Background Placebo-controlled clinical trials have demonstrated the efficacy of tocilizumab (TCZ) for remission maintenance and glucocorticoid sparing in patients with giant cell arteritis (GCA). However, limited data exist on the effectiveness and safety of TCZ for GCA in real-world clinical practice. Methods This was a retrospective, single-center analysis of patients with GCA treated with intravenous or subcutaneous TCZ (2010–2018). Outcomes evaluated before and after TCZ initiation included occurrence of flare, time to flare, annualized flare rate, flare characteristics (i.e., polymyalgia rheumatica [PMR] symptoms, cranial manifestations), prednisone use, and safety. Flare was defined as the recurrence of unequivocal GCA manifestations requiring treatment intensification. Subgroup analyses of patients with PMR or visual manifestations at GCA diagnosis were performed. Results Sixty patients with GCA were included. The median (IQR) disease duration before and after the start of TCZ was 0.6 (0.2–1.6) and 0.5 (0.3–1.4) years, respectively. At least 1 flare was observed in 43 patients (71.7%) before and in 18 (30.0%) after TCZ initiation. Median (IQR) time to flare was 0.5 (0.3–0.7) years before TCZ treatment and 2.1 (0.6–2.6) years after TCZ initiation (HR 0.22; 95% CI 0.10–0.50; p = 0.0003). The annualized flare rate significantly decreased following TCZ use (before TCZ 1.4 [95% CI 1.0–2.1]; after TCZ 0.6 [95% CI 0.3–1.0] events/year; p < 0.001). Similar improvements were observed in patients with visual manifestations or PMR symptoms at GCA diagnosis. TCZ reduced the incidence of new visual manifestations, and no flares associated with permanent vision loss occurred while patients were receiving TCZ. Mean (SD) prednisone dose at TCZ onset and at the end of follow-up was 30 (18.3) and 5 (6.9) mg/day, respectively (p < 0.0001). After TCZ initiation, 46.6% of patients successfully discontinued prednisone. The incidence of adverse events, primarily attributed to glucocorticoids, was similar before and after TCZ initiation. Conclusions In this real-world setting, TCZ improved GCA clinical outcomes significantly and demonstrated effectiveness in the subgroups of patients with PMR symptoms and GCA-related visual manifestations at GCA diagnosis. No new cases of blindness occurred after TCZ initiation. Adverse events, many attributable to glucocorticoids, were comparable before and after TCZ treatment.

Patients with RA receiving TCZ plus MTX who achieve low disease activity can discontinue MTX without significant worsening of disease activity during the 16 weeks following MTX discontinuation.

ObjectiveTwo randomised controlled trials, AMBITION (NCT00109408) and ADACTA (NCT01119859), showed tocilizumab (TCZ) monotherapy superior to methotrexate (MTX) and adalimumab (ADA) monotherapy, respectively, for improving rheumatoid arthritis (RA) disease activity. This study compared the benefit of TCZ versus MTX or ADA monotherapy for improving patient-reported outcomes (PROs) in patients with RA.MethodsPROs included patient global assessment (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and Short Form-36 (SF-36) physical component summary (PCS) and mental component summary (MCS) and eight domain scores. Outcomes included proportions of patients reporting changes from baseline in PRO scores ≥minimum clinically important differences (MCID) and ≥age-matched and gender-matched normative values at 24 weeks.ResultsIn AMBITION, TCZ-treated patients reported significantly greater mean improvements in HAQ (−0.7 vs −0.5), FACIT-Fatigue (8.7 vs 5.7), SF-36 PCS (9.8 vs 7.8) and five SF-36 domains at week 24 than with MTX; 45.0%–84.0% of TCZ-treated patients reported improvements ≥MCID, and 24.3%–52.1% reported scores ≥normative values across all PROs versus 39.4%–81.8% and 14.5%–45.0%, respectively, with MTX. In ADACTA, TCZ-treated patients reported significantly greater improvements in PtGA (−42.3 vs −31.8), pain (−40.1 vs −28.7), SF-36 MCS (7.9 vs 5.0) and three SF-36 domains than with ADA; 57.7%–83.3% of TCZ-treated patients reported improvements ≥MCID, and 22.1%–49.3% reported scores ≥normative values across all PROs versus 13.6%–37.8%, respectively, with ADA.ConclusionsTCZ monotherapy resulted in more patients reporting clinically meaningful PRO improvements and PRO scores ≥normative values compared with MTX or ADA monotherapy.Trial registration numbers NCT00109408 and NCT01119859; Post-results.

ObjectiveRandomised controlled trials (RCTs) have shown tocilizumab (TCZ) administered intravenously or subcutaneously with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to be superior to csDMARDs alone for improving rheumatoid arthritis (RA) disease activity. This study evaluated the effect of TCZ-intravenous and TCZ-subcutaneous on patient-reported outcomes (PROs) in three RCT populations.MethodsOPTION (NCT00106548), BREVACTA (NCT01232569) and SUMMACTA (NCT01194414) were independent RCTs evaluating the efficacy and safety of TCZ-intravenous and/or TCZ-subcutaneous with csDMARDs in patients with RA. PROs included patient global assessment, pain, Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue and Short Form-36. Study outcomes included the proportions of patients reporting changes from baseline in PRO scores ≥ minimum clinically important differences (MCID) and scores ≥ age and gender-matched normative values.ResultsIn OPTION, more patients who received TCZ-intravenous reported improvements in PROs ≥MCID (50%–82% vs 31%–57%) and scores ≥ normative values (16%–44% vs 5%–28%) at week 16 compared with placebo. Similarly, a greater proportion of patients in BREVACTA who received TCZ-subcutaneous reported improvements ≥ MCID (54%–73% vs 42%–55%) and scores ≥ normative values (8%–34% vs 4%–25%) at week 12 compared with placebo. In SUMMACTA, 61%–84% of patients who received TCZ-subcutaneous and 64%–84% of those who received TCZ-intravenous reported improvements ≥ MCID and 14%–41% and 15%–24%, respectively, scores ≥ normative values at week 24.ConclusionsTCZ-intravenous or TCZ-subcutaneous with csDMARDs resulted in more patients reporting clinically meaningful improvements and PRO scores ≥ normative values compared with placebo. These improvements were similar with TCZ-intravenous and TCZ-subcutaneous.

BackgroundTocilizumab (TCZ) is a recombinant humanized monoclonal antibody targeted against the interleukin-6 receptor that was approved to treat rheumatoid arthritis (RA) in the EU in 2009 and in the US in 2010. TCZ has now completed long-term extension (LTE) follow-ups in a number of intravenous and subcutaneous RA trials.ObjectivesTo provide an updated report on the incidence of safety events during TCZ treatment in patients with RA using data from multiple completed clinical trials and their LTEs, as well as to provide an update from the global TCZ postmarketing safety database.MethodsIncidence and reporting rates of adverse events (AEs) of special interest, including infections, malignancies, anaphylaxis, bleeding events, myocardial infarctions, gastrointestinal perforations, strokes, hepatic events and demyelination, were estimated from 2 distinct patient data sets. Incidence rates were calculated from 12 completed TCZ RA clinical trials and their LTE periods and are reported as events per 100 patient-years (PY). Reporting rates were also estimated from the global TCZ postmarketing safety database (Oct 2008 to Oct 2015), which includes information from all spontaneously reported cases and non-interventional programs as well as literature cases, and are reported as cases per 100 patients.ResultsThe clinical trial all-exposure population consisted of 7647 TCZ-treated patients with RA (81.6% female; mean [SD] age, 52 [12.6] years), constituting 22,394 PY (mean follow-up, 2.93 years) of exposure. The overall rate (95% CI) of serious AEs in the clinical trial population was 14.16 (13.67–14.66) per 100 PY. Overall incidence rates for individual events for the clinical trial population are reported in the Table and were consistent in each 6-month period over the 5-year duration. The global postmarketing population included 606,937 patients. The overall spontaneous reporting rate (range) of AEs of special interest in the postmarketing population was 9.37 (7.35–10.56) cases per 100 patients. Reporting rates of individual safety events of interest in the global postmarketing population are shown in the Table and were consistent in each 6-month period over the 7-year duration.ConclusionsThe safety profile of TCZ in the current analysis, which includes information about safety events from 12 clinical trials and their LTEs and across 7 years of real-world postmarketing reports encompassing $≈ $ 600,000 patients, was consistent with previous safety reports. These findings are consistent with the previously reported profile of TCZ and indicate that there is no evidence of increased safety risk with increasing exposure to TCZ.AcknowledgementsThis study was funded by F. Hoffmann-La Roche/Genentech, Inc.Disclosure of InterestS. Mohan Employee of: Genentech, Inc., M. Michalska Employee of: Genentech, Inc., J. Yourish Employee of: Genentech, Inc., J. Pei Employee of: Genentech, Inc., S. Gale Employee of: Genentech, Inc., C. Birchwood Employee of: Genentech, Inc., E. Berber Employee of: Genentech, Inc.