POS0808 CHARACTERISTICS OF GIANT CELL ARTERITIS FLARES AFTER SUCCESSFUL TREATMENT WITH TOCILIZUMAB: RESULTS FROM THE LONG-TERM EXTENSION OF A RANDOMIZED CONTROLLED PHASE 3 TRIAL

Abstract

Background:GiACTA investigated tocilizumab (TCZ) for the treatment of giant cell arteritis (GCA).Objectives:To investigate disease flare characteristics after successful treatment with TCZ in GiACTA.Methods:We report a post hoc analysis from part 2 of GiACTA. Part 1 was a 52-week, double-blind, randomized controlled period and part 2 was a 2-year open-label follow-up. In part 1, patients received TCZ 162 mg subcutaneously every week or every other week with a 26-week prednisone taper or placebo plus a 26- or 52-week prednisone taper. Patients who were in remission at week 52 were to enter part 2 on no TCZ treatment. Part 2 treatment was at the investigator’s discretion. We report characteristics of first disease flare in patients assigned to TCZ in part 1 who were in sustained remission at week 52 and experienced flare in part 2. Flare was defined as reappearance of cranial symptoms (headaches, jaw claudication, visual manifestations, scalp tenderness) or polymyalgia rheumatica (PMR) symptoms or elevation of erythrocyte sedimentation rate (ESR) ≥30 mm/h attributable to GCA that required treatment.Results:Of 149 patients assigned to TCZ in part 1, 81 (54%) were in sustained remission on entering part 2. Of these 81 patients, 37 (46%) experienced at least one flare in part 2, including 17 with new-onset GCA and 20 with relapsing GCA at baseline. Median time to flare was 26.6 weeks. In patients with new-onset GCA, flares included cranial (53%) more often than PMR symptoms (18%). Cranial and PMR symptoms were balanced (both 60%) at the time of flare in patients with relapsing GCA. Visual manifestations occurred in two patients (5%) (Table 1). ESR and CRP were elevated in 65% and 36% of patients, respectively, at the time of flare. Three (8%) flares occurred with elevated ESR without clinical symptoms.Table 1.Clinical manifestations during flare in part 2Part 1 TreatmentaTCZ QW+PredTCZ Q2W+PredAll TCZNew-onset diseasePatients, n281442Patients with ≥1 flare, n (%)b9 (32.1)8 (57.1)17 (40.5)Patients with ESR ≥30 mm/h during flare, n (%)b6 (66.7)6 (75.0)12 (70.6)Patients with CRP ≥10 mg/L during flare, n (%)b4 (44.4)2 (25.0)6 (35.3)Patients with GCA signs or symptoms during flare, n (%)c7 (77.8)7 (87.5)14 (82.4)PMR symptoms1 (11.1)2 (25.0)3 (17.6)Cranial symptomsd4 (44.4)5 (62.5)9 (52.9) Amaurosis fugax000 Blurred vision1 (11.1)01 (5.9) Diplopia000 Blindness000 Ischemic optic neuropathy000Fever1 (11.1)01 (5.9)Othere3 (33.3)2 (25.0)5 (29.4)Relapsing diseasePatients, n281139Patients with ≥1 flare, n (%)b14 (50.0)6 (54.5)20 (51.3)Patients with ESR ≥30 mm/h during flare, n (%)b8 (57.1)4 (66.7)12 (60.0)Patients with CRP ≥10 mg/L during flare, n (%)b5 (35.7)3 (50.0)8 (40.0)Patients with GCA signs or symptoms during flare, n (%)c14 (100)6 (100)20 (100)PMR symptoms8 (57.1)4 (66.7)12 (60.0)Cranial symptomsd8 (57.1)4 (66.7)12 (60.0)Amaurosis fugax1 (7.1)01 (5.0)Blurred vision000Diplopia000Blindness000Ischemic optic neuropathy1 (7.1)01 (5.0)Fever000Othere6 (4.3)1 (16.7)7 (35.0)aPatients from part 1 TCZ+Pred groups who were in sustained remission at week 52 entered part 2 on no treatment.bPercentage based on N in disease-onset group.cPercentage based on number of flare patients in disease-onset group. Individual signs or symptoms are shown as number of patients with each symptom; patients could have ≥1 sign or symptom at the time of flare.dNew-onset localized headache, scalp tenderness, temporal artery tenderness or decreased pulsation, ischemia-related vision loss, or jaw pain claudication.eIncludes fatigue, malaise, subjective weakness, and night sweats.Conclusion:Overall, 46% of GCA patients successfully treated with TCZ for 1 year experienced disease flare within the next 2 years. Flares in patients with new-onset disease occurred more often with cranial than PMR symptoms. Visual manifestations were rare, and no blindness occurred. ESR and CRP were normal in a sizable percentage of patients experiencing flare.Disclosure of Interests:Sebastian Unizony Consultant of: Sanofi and Kiniksa Pharmaceuticals, Grant/research support from: Genentech, Inc., Shalini Mohan Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Jian Han Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., John H. Stone Consultant of: Roche/Genentech and Sanofi