EULAR 2018 Review

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was no suggestion of an increased risk of serious infection in any absolute lymphocyte count category [#0330]. The third interim analysis of OPAL Balance, an open-label LTE study of tofacitinib in patients with PsA, was reported by Nash, et al. Of the 686 patients treated in the study, 468 remained in the study at data cut-off. To 36 months, 2186 AEs were reported in 79.6% of patients. SAEs, discontinuations due to AEs and serious infections were reported in 13.8%, 8.6% and 1.7% of patients, respectively. HZ was reported in 2.9% of patients, MACE in 0.7%, malignancies in 3.5% (including 12 pts with NMSC) and uveitis in 0.3%. No AEs of GI perforation or inflammatory bowel disease were reported. There were 5 deaths, none of which were attributed to treatment as assessed by the investigator. The authors concluded that over 36 months in the LTE, the safety profile of tofacitinib in patients with active PsA was generally similar to that of the Phase 3 studies. Efficacy was maintained across multiple disease domains to Month 30 [#0293]. Effect of tofacitinib on patient-reported outcomes in RA, PsA and AS Ogdie, et al. showed that tofacitinib treatment (5 mg BID or 10 mg BID) was associated with a rapid and sustained reduction of pain in patients with RA, PsA and AS. In patients with RA or PsA who were csDMARD-IR or TNFi-IR, mean Patient's Assessment of Arthritis Pain (PAAP)-VAS at baseline (5 mg BID, range 55.7–65.7 mm; 10 mg BID, 54.4–60.1 mm) decreased as early as Week 2 and continued to decrease through Month 6 (30.9–34.4 mm; 28.2–36.7 mm); decreases were numerically greater versus placebo and the magnitude of change was similar in RA and PsA populations. Improvements in SF-36v2 and EQ-5D were observed in all four RA and PsA csDMARD-IR and TNFi-IR populations; there were improvements in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in the csDMARD-IR PsA and TNFi-IR PsA populations. In the AS population, improvements from baseline in SF-36v2 Q7, SF-36v2 bodily pain (BP) domain, EQ-5D Pain/Discomfort (PD) domain and BASDAI Q2, were observed at Week 12 and were numerically greater than with placebo [#0221]. No evidence for increased risk of DVT or PE with tofacitinib across disease states Mease and colleagues reported an analysis of DVT and PE across randomised clinical studies of tofacitinib in patients with RA, PsO, PsA and ulcerative colitis (UC). Up to Month 3 in the placebo-controlled cohort, DVT and PE occurred in two patients receiving placebo (n=1 RA, n=1 UC); no tofacitinib-treated patients had DVT or PE events. In the dose comparison cohort, 2 DVT events occurred in tofacitinib-treated patients with RA (5 mg BID, n=1; 10 mg BID, n=1) and 1 DVT event in a patient with PsA (10 mg BID, n=1); 2 DVT events occurred with MTX and none with adalimumab. With tofacitinib, 5 PE events occurred in the dose comparison cohort, all in patients with RA (5 mg BID, n=2; 10 mg BID, n=3). The authors concluded that there is no evidence for an increased risk of these events with tofacitinib versus other therapies [#0243].
Baricitinib dose step-down following sustained disease control The effects of baricitinib dose step-down in patients with RA who achieved sustained disease control with baricitinib 4 mg were presented by Takeuchi, et al. Patients who participated in the baricitinib Phase 3 LTE study and received baricitinib 4 mg for ≥15 months, and achieved LDA or remission, were re-randomised to continue baricitinib 4 mg (n=374) or step-down to baricitinib 2 mg (n=376); patients could rescue to 4 mg. Most patients in both groups maintained LDA or remission over the 48 weeks; however, dose reduction to 2 mg resulted in significant increases in disease activity at 12, 24 and 48 weeks, and a shorter time to relapse compared with the 4-mg group. Rates of SAEs and AEs leading to discontinuation were similar between groups; however, dose reduction was associated with a lower rate of serious infections. Most rescued patients were able to regain LDA or remission [#0253]. Baricitinib: HBV reactivation and autoantibody profiling Harigai and colleagues presented the findings of a post hoc analysis examining hepatitis B virus (HBV) reactivation in patients with RA who participated in 4 Phase 3 trials of baricitinib. In a total of 2890 patients who received 1 or more dose of baricitinib (6993 patient-years exposure), 269 patients had baseline serology suggestive of prior infection and post-baseline HBV DNA tests were performed in 290 patients. Approximately 12% of baricitinib-treated patients with prior HBV infection later tested positive for HBV DNA (3% were above the lower limit of detection); no patients developed clinical evidence of hepatitis, and antiviral therapy was not commonly required [#0077]. An exploratory analysis of autoantibody profiles for response to baricitinib in patients with RA and no or limited exposure to MTX was presented by Martinez-Gamboa, et al. Baseline sera samples from patients participating in the Phase 3 trial RA-BEGIN were investigated for auto-antibody class reactivity towards vimentin (V), modified by citrullation (MCV), carbamylation (Carb) or acetylation. Seropositive patients with high titres of anti-MCV and anti-CarbV at baseline showed better responses to baricitinib monotherapy or baricitinib plus MTX for composite scores, and better response to baricitinib monotherapy in structural progression outcomes [#0109] Patient-reported outcomes with baricitinib Bingham and colleagues reported an analysis of PROs from the Phase 3 RA-BEAM and RA-BEACON trials of baricitinib in patients with RA with an inadequate response to MTX. FACIT-F and SF-36 BP scores were converted to Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue and Pain Interference (PI) scores, to permit comparisons with the general population. In both studies, baricitinib was associated with clinically relevant improvements through 24 weeks versus placebo for PROMIS fatigue and PI scores [#0106]. In a separate analysis, the authors converted HAQ-DI scores to PROMIS Physical Function (PF) scores. Treatment with baricitinib was associated with clinically relevant improvements in PROMIS PF versus placebo through 24 weeks in both studies, and versus adalimumab through 52 weeks in RA-BEAM [#0013].
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EULAR 2018 Review

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