SAT0439 Integrated safety summary of tofacitinib in psoriatic arthritis clinical studies

Abstract

BackgroundTofacitinib is an oral Janus kinase inhibitor under investigation for psoriatic arthritis (PsA).ObjectivesTo describe the safety profile of tofacitinib from integrated Phase (P)3 and long-term extension (LTE) studies.MethodsData were analysed for patients (pts) who received ≥1 dose of tofacitinib 5 or 10 mg BID or placebo (PBO), integrated across 2 P3 studies (OPAL Broaden [12 months; NCT01877668]; OPAL Beyond [6 months; NCT01882439]) and 1 LTE study (OPAL Balance [ongoing, database not locked; NCT01976364]). Common adverse events (AEs; occurring in ≥2% of tofacitinib pts in any group) were analysed in the PBO-controlled portion (Months 0–3) of the P3 studies (Cohort 1 [C1]). Serious AEs (SAEs) and discontinuations due to AEs were analysed over 12 months in pts randomised to tofacitinib 5 or 10 mg BID in P3 studies (Cohort 2a [C2a]); pts randomised to PBO were excluded from this analysis. Deaths and AEs of special interest (serious infections [SI], herpes zoster [HZ], opportunistic infections [OI] including HZ, major adverse cardiac events [MACE], malignancies, non-melanoma skin cancer [NMSC]) were evaluated in all tofacitinib-treated pts in the P3 and LTE studies (Cohort 3 [C3]). Incidence rates (IR; pts with events/100 pt-years [PY] and 95% confidence intervals) are reported. Laboratory results will be reported in future publications.ResultsC1 included 474 tofacitinib- and 236 PBO-treated pts; C2a included 474 tofacitinib-treated pts; and C3 included 783 tofacitinib-treated pts (exposure: 776 PY). Nasopharyngitis (5.9%) and headache (8.5%) were the most commonly reported AEs at Month 3 in pts receiving tofacitinib 5 and 10 mg BID, respectively (Table). In pts randomised to tofacitinib 5 or 10 mg BID, over 12 months (C2a), the IRs for SAEs were 7.92 (4.09, 13.84) and 8.11 (4.19, 14.17), respectively. Discontinuation due to AEs occurred in 11 (4.6%) and 11 (4.7%) pts randomised to tofacitinib 5 and 10 mg BID, respectively, with IRs of 7.16 (3.58, 12.82) and 7.31 (3.65, 13.08), respectively, over 12 months (C2a). Across all tofacitinib-treated pts in the P3 and LTE studies (C3), SIs occurred in 11 pts (1.4%; IR 1.40 [0.70, 2.50]). HZ was reported in 16 pts (2.0%; IR 2.05 [1.17, 3.33]) receiving tofacitinib. All 3 cases of multidermatomal HZ were adjudicated as OIs; these were the only OIs (0.4%; IR 0.38 [0.08, 1.11]). In C3, 2 deaths occurred (0.3%; IR 0.25 [0.03, 0.91]); all were considered unrelated to the study drug. MACE were reported in 3 pts (0.4%; IR 0.38 [0.08, 1.11]), malignancies (excluding NMSC) in 5 pts (0.6%; IR 0.63 [0.21, 1.48]) and NMSC in 4 pts (0.5%; IR 0.51 [0.14, 1.30]).ConclusionsTofacitinib was well tolerated in pts with PsA, with a safety profile consistent to that seen in RA; no new risks were identified. Longer-term follow-up and larger pt populations will provide further information on the safety profile of tofacitinib in pts with PsA.AcknowledgementsThese studies were sponsored by Pfizer Inc. Editorial support was provided by C Viegelmann of CMC and was funded by Pfizer Inc.Disc...

Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis

“…[53,54] JAK inhibition with tofacitinib showed higher rates of herpes zoster (IR 2.05; 95% CI 1.17-3.33) and MACE were reported in three patients (IR 0.38; 95% CI 0.08-1.11). [55] One case of herpes zoster and one MACE were observed in patients treated with filgotinib (vs. none in the placebo group). [13] While no venous thromboembolic events or pulmonary embolisms were observed in PsA patients treated with tofacitinib or filgotinib, [13,55] such events were seen in other indications when tofacitinib, baricitinib and upadacitnib were used, especially in an ongoing study in RA patients with high cardiovascular risk (tofacitinib study A3921133); warnings in these regards were issued by regulators, especially with respect to patients with a high risk for venous thromboembolic events.…”

“…[55] One case of herpes zoster and one MACE were observed in patients treated with filgotinib (vs. none in the placebo group). [13] While no venous thromboembolic events or pulmonary embolisms were observed in PsA patients treated with tofacitinib or filgotinib, [13,55] such events were seen in other indications when tofacitinib, baricitinib and upadacitnib were used, especially in an ongoing study in RA patients with high cardiovascular risk (tofacitinib study A3921133); warnings in these regards were issued by regulators, especially with respect to patients with a high risk for venous thromboembolic events. [56,57] This SLR has several limitations: (1) abstract screening, report analysis, risk of bias analysis and data extraction were performed by one researcher only (A.K.…”

<p>Tofacitinib in the management of active psoriatic arthritis: patient selection and perspectives</p>

“…Integrated safety analyses of phase III studies 38 and the LTE study 22 found tofacitinib to be well tolerated in patients with psoriatic arthritis with a safety profile that is comparable to other biologics. 11,39 The adverse events reported in psoriatic arthritis trials were similar to those reported for rheumatoid arthritis and psoriasis.…”

“…11,39 The adverse events reported in psoriatic arthritis trials were similar to those reported for rheumatoid arthritis and psoriasis. 38,39 The most common adverse events reported in the phase III trials were upper respiratory infections, nasopharyngitis, and headaches. 11,12 Tofacitinib has been associated with an increased risk of herpes zoster, which occurred in the active treatment group of both trials.…”

Efficacy of Tofacitinib for the Treatment of Psoriatic Arthritis: Pooled Analysis of Two Phase 3 Studies

“…Additionally, with respect to the statistical analyses, p values were generated with no correction for multiplicity. Finally, this analysis focuses on the efficacy of tofacitinib in treating PsA; safety data are reported in the primary manuscripts [ 20 , 21 ] as well as in a pooled safety analysis [ 30 ]. No new safety risks were identified in an interim analysis of data from patients with active PsA receiving tofacitinib for up to 36 months in the ongoing LTE study, OPAL Balance (NCT01976364; data-cut: November 2017; database not locked; data may change) [ 31 ].…”