EULAR 2018 Review

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for discontinuing tofacitinib were insufficient response (n=23), GI symptoms (n=18), infection (n=5), myalgia (n=2), remission (n=2), headache (2), cough, blue toe syndrome, intolerance, heart burn, psoriasis, and increased liver enzymes (all n=1). The authors concluded that tofacitinib is a safe and effective treatment option for patients with RA [#0497]. Zengin and colleagues reported data from the Turkish TURKBIO registry on tofacitinib efficacy and safety in 180 patients with RA. Median duration of disease activity was 14 years, and 75 patients had previously used ≥1 biologic agent. All disease activity parameters were significantly reduced versus baseline after 12 weeks of treatment, with 6%, 59% and 27% of patients achieving remission, or with a moderate or high activity level, respectively. Most disease activity parameters were maintained until Week 60, the last examined time point. During the follow-up period, 9 AEs were observed [#0482]. Drug survival rates with tofacitinib in RA: a single-centre cohort study Drug survival rates of tofacitinib in a single-centre cohort of 192 patients with RA with a median disease duration of 10 years were reported by Karakoc, et al. Approximately half of the cohort (48%) were biologic-naïve; tofacitinib was prescribed as monotherapy in 58% of patients and in combination with csDMARDs in 42% of patients. Drug survival rates were 77% at 3 months, 69% at 6 months, 62% at 12 months, 54% at 18 months, 49% at 24 months and 49% at 30 months. Discontinuation of tofacitinib treatment occurred in 27% of patients due to lack of response, and in 11% of patients due to side effects [#0502]. Tofacitinib dose escalation and subsequent reduction in patients with RA Gaylis and colleagues reported data from a study of nine patients who were initially unresponsive to treatment with tofacitinib 5 mg BID and who were subsequently dose escalated to 10 mg BID to achieve LDA or remission. After 6 months of treatment with 10 mg BID and a sustained LDA or remission, the patients were reduced back to 5 mg BID; six of nine patients were able to maintain LDA or remission over the following 6 months, and three patients were dose escalated back to 10 mg BID and achieved treatment target. These findings confirm that 10 mg BID of tofacitinib may be the effective dose required to reach treatment target for some patients with active RA and suggest that there is opportunity to reduce the escalated dose back down to the standard dose following achievement of a target response [#0282]. Improvement of left ventricular mass and cardiac output with tofacitinib In a cohort study, Kume, et al. showed that tofacitinib monotherapy improved left ventricular mass and cardiac output in 24 patients with active RA (despite treatment with csDMARDs) and chronic heart failure. Tofacitinib significantly attenuated left ventricular mass as measured with cardio-MRI at baseline and 24 weeks; these effects were independent of tofacitinib’s effects on disease activity. The authors propose that the JAK- STAT pathway may be important for left ventricular hypertrophy, and that blockade of this pathway by tofacitinib may prevent cardiovascular morbidity and mortality in patients with RA and chronic heart failure [#0489].
A case study of vasculitis in a patient with RA treated with tofacitinib Muraviev, et al. presented a case of polyarteritis nodosa (vasculitis) in a female patient with RA. The patient was hospitalised in December 2016 due to painful eruption of indurated nodules on her legs, ulceration of nodules on her legs, painful hip and ankle joints and morning stiffness; the patient had been receiving tofacitinib 10 mg/day since November 2015, with rapid achievement of minimum RA activity. Tofacitinib was discontinued in June 2016 due to increasing lab activity of vasculitis. Histopathology showed the presence of cutaneous and subcutaneous fat and destructive vasculitis, and acute, predominantly lobular panniculitis, suggestive of polyarteritis nodosa and other systemic vasculitis. A causal relationship between this adverse drug reaction and tofacitinib therapy was assessed as probable (Naranjo scale) [#0413]. Musculoskeletal ultrasound for monitoring the effects of biologic therapy in RA Yu and colleagues reported that musculoskeletal ultrasound (MSUS) was a useful tool for monitoring and following-up the effects of biologic therapy in patients with RA, for the assessment of inflammatory and destructive changes. In a real-world study of 18 patients with RA who were treated with tofacitinib 5 mg BID for 12 weeks, there was a significant correlation between MSUS scores and conventional (clinical and laboratory) measures of disease activity [#0210]. Tofacitinib in patients with PsA: pooled sub-analyses of OPAL Broaden and OPAL Beyond Kivitz, et al. investigated pooled data from OPAL Broaden and OPAL Beyond, looking at the efficacy of tofacitinib by background MTX dose in patients with PsA. In total, data from 556 patients who received tofacitinib plus MTX or placebo plus MTX were included in this analysis. Most patients were treated with background MTX at doses ≤15 mg/week (66.7%; mean dose 12.6 mg/week) compared with >15 mg/week (33.3%; mean dose 19.8 mg/week). At Month 3, tofacitinib 5 and 10 mg BID were generally associated with numerically greater ACR and HAQ-DI response rates and greater changes from baseline in HAQ-DI score compared with placebo. The magnitude of tofacitinib effects on efficacy outcomes appeared broadly similar between background MTX dose groups [#0902]. In a second pooled sub-analysis of the OPAL Broaden and OPAL Beyond studies, Behrens and colleagues examined the impact of baseline demographics, disease activity and concomitant medication on ACR20 response rate and HAQ-DI. Compared with placebo, tofacitinib 5 and 10 mg BID consistently improved efficacy at Month 3 across all predefined subgroups evaluated (race, ethnicity, gender, geographic region, PsA duration, age, BMI, PsA subtype, distal inter-phalangeal joint involvement, arthritis mutilans status, spondylitis status, baseline CRP, PASDAS, PASI score, DSS=0, concomitant csDMARD, corticosteroid use), with the exception of current smoking status [#0921]. A novel mechanism of action for tofacitinib Marzaioli, et al. reported preclinical results suggesting a novel mechanism of action for tofacitinib. Pre-treatment of monocyte-derived dendritic cells (Mo-DC) from patients with RA and PsA inhibited Mo-DC differentiation. Furthermore, the decreased ability of
Page 1 and 2: Enhancing knowledge of the clinical
Page 3 and 4: Highlights from EULAR 2018 During t
Page 5 and 6: Poster Sessions Poster Tour: Novel
Page 7 and 8: Poster sessions I, II and III Upada
Page 9 and 10: treatment with tofacitinib lead to
Page 11 and 12: Baricitinib dose step-down followin
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