Selective JAK inhibitors in development for rheumatoid arthritis

Norman, Peter

doi:10.1517/13543784.2014.918604

Cited by 137 publications

(121 citation statements)

References 45 publications

Supporting

Mentioning

117

Contrasting

Unclassified

Order By: Relevance

“…Baricitinib is a potent, selective, orally administered, reversible inhibitor of JAK signaling 6 . In contrast to other JAK inhibitors 7,8 , baricitinib has similar inhibitory activity for both JAK1 [50% Inhibitory Concentration (IC50) 5.9 nM] and JAK2 (IC50 5.7 nM), but much less activity against JAK3 (IC50 > 400 nM) and tyrosine kinase 2 (IC50 53 nM) 6 in isolated enzyme assays.…”

mentioning

confidence: 88%

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study

Tanaka

Emoto²,

Chen³

et al. 2016

J Rheumatol

115

View full text Add to dashboard Cite

Objective.To evaluate efficacy and safety, baricitinib [Janus kinase (JAK) 1/JAK2 inhibitor] was compared with placebo in Japanese patients with active rheumatoid arthritis (RA) despite background treatment with methotrexate (MTX).Methods.This was a phase IIB, double-blind, randomized, placebo-controlled study (clinicaltrials.gov: NCT01469013). Patients had moderate to severe active adult-onset RA despite stable treatment with MTX. Patients (n = 145) were randomized in a 2:1:1:1:1 ratio to placebo or 1 mg, 2 mg, 4 mg, or 8 mg oral baricitinib daily for 12 weeks. The primary analysis compared the combined 4/8-mg dose groups with placebo for the American College of Rheumatology (ACR) 20 response rate at 12 weeks. Other outcomes included additional measures of disease activity, physical function, laboratory abnormalities, and adverse events.Results.A significantly higher proportion of patients in the combined 4/8-mg baricitinib group (37/48, 77%) compared with the placebo group (15/49, 31%) had at least an ACR20 response after 12 weeks of treatment (p < 0.001). Significant improvements in disease activity, remission, and physical function were observed as early as Week 2 of treatment with baricitinib, particularly with daily doses of ≥ 4 mg. Only 1 patient receiving baricitinib discontinued because of an adverse event. Adverse event rates with baricitinib doses ≤ 4 mg daily were similar to placebo, but there was a higher incidence of adverse events and laboratory abnormalities in the 8-mg group.Conclusion.In this phase II study, baricitinib was well tolerated and rapidly improved the signs, symptoms, and physical function of Japanese patients with active RA, supporting continued development of baricitinib (clinicaltrials.govNCT01469013).

show abstract

mentioning

confidence: 88%

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study

Tanaka

Emoto²,

Chen³

et al. 2016

J Rheumatol

115

View full text Add to dashboard Cite

show abstract

“…JAK inhibitors are low-molecular-weight products that can be administered orally. The pan-JAK inhibitor tofacitinib has been approved by the US Food and Drug Administration for use in patients with moderately to severely active RA as a second-line agent after methotrexate (MTX), and other JAK inhibitors are in development 8 9. Filgotinib (GLPG0634/GS-6034) is a potent and selective inhibitor of JAK1,10–12 currently under investigation for the treatment of RA and inflammatory bowel disease.…”

Section: Introductionmentioning

confidence: 99%

Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1)

Westhovens¹,

et al. 2016

View full text Add to dashboard Cite

ObjectivesTo evaluate the efficacy and safety of different doses and regimens of filgotinib, an oral Janus kinase 1 inhibitor, as add-on treatment to methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and inadequate response to MTX.MethodsIn this 24-week phase IIb study, patients with moderate-to-severe active RA receiving a stable dose of MTX were randomised (1:1:1:1:1:1:1) to receive placebo or 50, 100 or 200 mg filgotinib, administered once daily or twice daily. Primary end point was the percentage of patients achieving a week 12 American College of Rheumatology (ACR)20 response.ResultsOverall, 594 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib 100 mg once daily or 200 mg daily (both regimens) achieved an ACR20 response versus placebo. For other key end points at week 12 (ACR50, ACR-N, Disease Activity Score based on 28 joints and C reactive protein value, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index), differences in favour of 100 or 200 mg filgotinib daily were seen versus placebo; responses were maintained or improved through to week 24. Rapid onset of action and dose-dependent responses were observed for most efficacy end points and were associated with an increased haemoglobin concentration. No significant differences between once-daily and twice-daily regimens were seen. Treatment-emergent adverse event rates were similar in placebo and filgotinib groups. Serious infections occurred in one and five patients in the placebo and filgotinib groups, respectively. No tuberculosis or opportunistic infections were reported.ConclusionsFilgotinib as add-on to MTX improved the signs and symptoms of active RA over 24 weeks and was associated with a rapid onset of action. Filgotinib was generally well tolerated.Trial registration number:NCT01888874.

show abstract

“…One tsDMARD that has been approved for patients with RA who have an inadequate response to csDMARDs is the JAK inhibitor tofacitinib -a small molecule that is a more potent inhibitor of JAK1 and JAK3 than JAK2, and can be taken orally [11,12]. Baricitinib is a JAK inhibitor that can also be taken orally, but it differs from tofacitinib in that it is selective for JAK1 and JAK2 [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of baricitinib in Japanese patients with rheumatoid arthritis: Subgroup analyses of four multinational phase 3 randomized trials

Tanaka

Atsumi

Amano

et al. 2017

Modern Rheumatology

View full text Add to dashboard Cite

show abstract

Selective JAK inhibitors in development for rheumatoid arthritis

Cited by 137 publications

References 45 publications

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study

Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1)

Efficacy and safety of baricitinib in Japanese patients with rheumatoid arthritis: Subgroup analyses of four multinational phase 3 randomized trials

Contact Info

Product

Resources

About