The effect of secukinumab on patient-reported outcomes in patients with active psoriatic arthritis in a randomised phase 3 trial

Strand V, Kaeley GS, Bergman MJ, Gladman DD, Coates LC, Sherif B, Hur P, Parikh B, Gilloteau I, Mease PJ.
Lancet. 2022. Epub ahead of print

Predefined analysis of FUTURE 5, the largest Phase 3 randomised trial of secukinumab in patients with PsA to date, demonstrates that secukinumab results in early, statistically significant, clinically meaningful, sustained improvements in PROs across all doses, compared with placebo. The fully human anti-interleukin 17A monoclonal antibody, secukinumab has shown clinical and radiographical efficacy in patients with PsA, yet the clinical significance of improvements across a wide variety of PROs...

Median Time to Pain Improvement and the Impact of Baseline Pain Severity on Pain Response in Patients with Psoriatic Arthritis Treated with Tofacitinib

de Vlam K, Ogdie A, Bushmakin AG, Cappelleri JC, Fleischmann R, Taylor PC, Azevedo V, Fallon L, Woolcott J, Mease PJ.
RMD Open. 2021;7(2):e001609.

Tofacitinib 5 mg twice daily provides clinically meaningful improvements in pain for patients with PsA. Reducing pain is a primary treatment concern for patients with PsA. As such, de Vlam, et al. set out to evaluate the time to pain improvement and the impact of baseline pain severity on pain response in patients with PsA receiving tofacitinib. Using data from the OPAL Broaden and OPAL Beyond trials, they discovered that clinically important improvements in pain were experienced by more patie...

Upadacitinib in Patients with Psoriatic Arthritis and Inadequate Response to Biologics: 56-Week Data from the Randomized Controlled Phase 3 SELECT-PsA 2 Study

Mease PJ, Lertratanakul A, Papp KA, van den Bosch FE, Tsuji S, Dokoupilova E, Keiserman MW, Bu X, Chen L, McCaskill RM, Zueger P, McDearmon-Blondell EL, Pangan AL, Tillett W.
Rheumatol Ther. 2021;8(2):903–919

Fifty-six-week data suggest that upadacitinib could be a favourable long-term treatment option in patients with PsA who are refractory to biologic therapy. As the need for additional therapeutic agents that can effectively control disease activity continues, new data from a 56-week analysis of the oral reversible JAK1 inhibitor, upadacitinib, currently under investigation for the treatment of PsA, shows that efficacy of the drug is maintained over the duration of this study. Mease, et al. expl...

Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2

Mease PJ, Lertratanakul A, Anderson JK, Papp K, Van den Bosch F, Tsuji S, Dokoupilova E, Keiserman M, Wang X, Zhong S, McCaskill RM, Zueger P, Pangan AL, Tillett W.
Annals of the rheumatic diseases. 2021 Mar 1;80(3):312-20.

In this trial of patients with active PsA who had inadequate response or intolerance to at least one biologic DMARD, upadacitinib 15 mg and 30 mg was more effective than placebo over 24 weeks in improving signs and symptoms of PsA. Despite the availability of bDMARDs in PsA, only a small proportion of patients achieve the recommended target of minimal disease activity; as such, additional treatment options are needed. Upadacitinib is under evaluation for PsA. This paper reports the 24-week data...

Incidence of venous and arterial thromboembolic events reported in the tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis development programmes and from real-world data

Mease P, Charles-Schoeman C, Cohen S, Fallon L, Woolcott J, Yun H, Kremer J, Greenberg J, Malley W, Onofrei A, Kanik KS, Graham D, Wang C, Connell C, Valdez H, Hauben M, Hung E, Madsen A, Jones TV, Curtis JR.
Annals of the Rheumatic Diseases 05 August 2020 2020 Nov;79(11):1400-1413. doi: 10.1136/annrheumdis-2019-216761. Epub 2020 Aug 5.

Concerns surrounding increased rates of PE and cardiovascular associated deaths has led to black box warnings when prescribing JAK inhibitors. As such, ongoing investigations regarding cardiovascular and VTE event risks in JAK inhibitor therapies, both clinical and real-world, are vital. Mease and colleagues consider data from clinical tofacitinib development programmes, and the ongoing real-data study A3921133. Conclusions from data analysis state that those with pre-existing cardiovascular and...

Safety and Efficacy of Tofacitinib in Patients with Active Psoriatic Arthritis: Interim Analysis of OPAL Balance, an Open-Label, Long-Term Extension Study

Nash P, Coates LC, Kivitz AJ, Mease PJ, Gladman DD, Covarrubias-Cobos JA, FitzGerald O, Fleishaker D, Wang C, Wu J, Hsu M, Menon S, Fallon L, Romero AB, Kanik KS.
Rheumatol Ther 2020 doi.org/10.1007/s40744-020-00209-4

This 3-year, open-label, LTE study follows PsA patients previously treated in pivotal studies OPAL Broaden and OPAL Beyond. It demonstrates maintained safety and efficacy of tofacitinib up to 36 and 30 months, respectively. No new safety concerns are highlighted. Previous P3 studies, OPAL Broaden and OPAL Beyond, demonstrated safety and efficacy of 5mg and 10mg tofacitinib BID in PsA. These patients rolled over to OPAL Balance for a period of 36 months. 686 participants were used in this inter...

Efficacy and Safety of Filgotinib, a Selective Janus Kinase 1 Inhibitor, in Patients with Active Psoriatic Arthritis (EQUATOR): Results from a Randomised, Placebo-controlled, Phase 2 Trial

Mease P, Coates LC, Helliwell PS, Stanislavchuk M, Rychlewska-Hanczewska A, Dudek A, Abi-Saab W, Tasset C, Meuleners L, Harrison P, Besuyen R, Van der Aa A, Mozafarian N, Greer JM, Kunder R, Van den Bosch F, Gladman DD.
Lancet. 2018 Dec 1;392(10162):2367-2377. DOI 10.1016/ S0140-6736(18)32483-8

In this first clinical trial of filgotinib in patients with PsA, filgotinib was effective in treating the signs and symptoms of active PsA across various disease manifestations. The EQUATOR trial was a randomized, double-blind, placebo-controlled, Phase 2 trial, that enrolled 191 adult patients from 25 sites in seven countries. Patients with active moderate-to-severe PsA and an insufficient response or intolerance to at least one csDMARD were assigned 1:1 to receive filgotinib 200 mg or placebo...

Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis

Mease P, Hall S, FitzGerald O, van der Heijde D, Merola J F, Avila-Zapata F, Cieslak D, Graham D, Wang C, Menon S, Hendrikx T, Kanik K S.
N Engl J Med 2017; 377:1537-50. DOI: 10.1056/NEJMoa1615975

In the Phase 3 OPAL Broaden trial of patients with active psoriatic arthritis (PsA) with inadequate response to ≥1 csDMARD, superior efficacy was observed in patients treated with tofacitinib (TOF) compared with those given placebo. Patients were randomised to: 5 mg TOF BID, 10 mg TOF BID, 40 mg adalimumab administered subcutaneously q2W, or placebo with a switch to 5 mg TOF at Month 3. Adalimumab was used as an active control in the study. A variety of primary and secondary endpoints wer...

Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors

Gladman D, Rigby W, Azevedo VF, Behrens F, Blanco R, Kaszuba A, Kudlacz E, Wang C, Menon S, Hendrikx T, Kanik KS.
N Engl J Med 2017;377:1525–36.

The study data presented that tofacitinib (TOF) improves efficacy response rates in patients with severe psoriatic arthritis (PsA) who have an inadequate response to TNF inhibitors. The Phase 3 Oral Psoriatic Arthritis Trial (OPAL) Beyond study evaluated patients with active PsA who had inadequate responses to more than one TNFi. Patients were randomised 2:2:1:1 to 5 mg TOF BID or 10 mg TOF BID for 6 months; or PBO, with a switch to 5 mg TOF BID or to 10 mg BID at 3 months. Primary endpoints w...

Metotreksata yetersiz cevap veren, orta-ağır romatoid artritli hastalarda subkutan clazakizumabın etkinliği ve güvenliği: Faz IIb, randomize, çift kör, plasebo/aktif kontrollü, doz aralıklı, çok uluslu bir çalışmanın sonuçları

Weinblatt ME, Mease P, Mysler E, Takeuchi T, Drescher E, Berman A, Xing J, Zilberstein M, Banerjee S, Emery P.
Arthritis & Rheumatology. 2015 Jul 2. doi: 10.1002/art.39249. [Epub ahead of print]

The humanised monoclonal antibody, Clazakizumab (CLZ), binds to circulating interleukin-6 (IL-6) cytokine rather than the IL-6 receptor, blocking both classical and trans-signalling. The purpose of this phase 2B study was to evaluate the efficacy and safety of clazakizumab in patients with inadequate response to methotrexate (MTX). Data on selected response rates – ACR20/50/70, DAS28-CRP, SDAI ≤3.3, CDAI ≤2.8 and the ACR/EULAR Boolean definition – and adverse events were collec...

Keywords: IL-6, Clazakizumab, Clinical, Phase 2

Translated by: Şafak Mirioğlu

JAK inhibitörü tofacitinib romatoid artritte sinovyal JAK1-STAT sinyalizasyonunu baskılar

Boyle DL, Soma K, Hodge J, Kavanaugh A, Mandel D, Mease P, Shurmur R, Singhal AK, Wei N, Rosengren S, Kaplan I, Krishnaswami S, Luo Z, Bradley J, Firestein GS.
Ann Rheum Dis. 2014 Nov 14. pii: annrheumdis-2014-206028. doi: 10.1136/annrheumdis-2014-206028. [Epub ahead of print]

Targeting intracellular pathways such as JAK/STAT represents a novel approach to the treatment of RA. Tofacitinib is an oral JAK inhibitor, proven to be effective in the treatment of RA, yet the pathways affected by tofacitinib and the effects on gene expression in situ are unknown. In this study, Boyle et al. tested the hypothesis that tofacitinib targets cytokine signalling critical to the pathogenesis of rheumatoid synovitis by investigating tofacitinib effects on synovial pathobiology. A...

Keywords: JAK, Tofacitinib, Preclinical, MOA

Translated by: Ege Sinan TORUN