Baricitinib at the ACR 2015 Meeting in San Francisco

There have been seven publications on Baricitinib at the ACR 2015 Annual Meeting in San Francisco. Baricitinib is an oral inhibitor of Janus kinases selective for JAK 1 and 2.

The first study is a three arm study: baricitinib versus placebo or adalimumab. The study was published as a late breaking abstract. Peter C. Taylor and colleagues presented the results of a phase 3 study. In methods we read: "Pts with active RA (TJC≥6 & SJC≥6 & hsCRP≥6 mg/L) despite stable background MTX were randomized 3:3:2 to PBO, bari 4 mg once daily (QD), or adalimumab (ADA) 40 mg biweekly (Q2W), stratified by region and baseline joint erosion status. [...]" Conclusion: "In pts with active RA despite background MTX, once-daily oral bari was associated with significant clinical improvements compared to PBO and to ADA, with an acceptable safety and tolerability profile." There seems to be a slight advantage of baricitinib compared to adaliimumab.

Xin Zhang and colleagues worked on: "Evaluate the Dose Efficacy Response Relationship of Baricitinib in Patients with Rheumatoid Arthritis". The authors identified 4 mg QD identified as the preferred phase 3 dose, "splitting the dose into a BID regimen does not provide any advantage over QD dosing for any of the efficacy endpoints."

Roy Fleischmann and colleagues looked at: "Baricitinib, Methotrexate, or Baricitinib Plus Methotrexate in Patients with Early Rheumatoid Arthritis Who Had Received Limited or No Treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARDs): Phase 3 Trial Results". Study over 24 weeks. Conclusion: "In pts with early RA, all treatment groups experienced improvements in disease activity with bari 4 mg monotherapy producing significantly larger and more rapid improvements and higher rates of clinical remission compared to MTX monotherapy, with a satisfactory safety profile. MTX addition to bari 4 mg did not increase the benefit observed with bari monotherapy, while it appeared to increase the frequency of laboratory abnormalities." As methotrexate isn't tolerated by all patients, this could make baricitinib interesting.

Mark C. Genovese and colleagues presented: "Previous Biologic Disease-Modifying Antirheumatic Drug (bDMARD) Exposure and Efficacy and Safety Analysis from a Phase 3 Study of Baricitinib in Patients with Rheumatoid Arthritis and an Inadequate Response to Tumor Necrosis Factor Inhibitors". This post hoc analysis didn't reveal any "evidence of a qualitative interaction".

There were three more studies: Paul Emery and colleagues (Characterization of Changes in Lymphocyte Subsets in Baricitinib-Treated Patients), Joel Kremer et al. (Response to Baricitinib at 4 Weeks Predicts Response at 12 and 24 Weeks), and Paul Emery and colleagues (Patient-Reported Outcomes from a Phase 3 Study of Baricitinib). Please see below for access to these studies.

Lots of interesting data! A new drug against rheumatoid arthritis has appeared on the horizon. But ... the evaluated and published data ends after 24 weeks. And there's no data yet on how successful baricitinb is concerning minimizing radiographic progression. Still some time needed before approval as a drug may be discussed. Anyway: good luck, baricitinib!

References:

Taylor PC, Keystone EC, van der Heijde D, Tanaka Y, Ishii T, Emoto K, Yang L, Arora V, Gaich CL, Rooney T, Schlichting DE, Macias W, de Bono S, Weinblatt ME. Baricitinib Versus Placebo or Adalimumab in Patients with Active Rheumatoid Arthritis (RA) and an Inadequate Response to Background Methotrexate Therapy: Results of a Phase 3 Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/baricitinib-versus-placebo-or-adalimumab-in-patients-with-active-rheumatoid-arthritis-ra-and-an-inadequate-response-to-background-methotrexate-therapy-results-of-a-phase-3-study/. Accessed November 20, 2015.

Zhang X, Chua L, Ernest CS II, Macias W, Rooney T, Tham LS. Evaluate the Dose Efficacy Response Relationship of Baricitinib in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/evaluate-the-dose-efficacy-response-relationship-of-baricitinib-in-patients-with-rheumatoid-arthritis/. Accessed November 20, 2015.

Fleischmann R, Takeuchi T, Schlichting DE, Macias WL, Rooney T, Gurbuz S, Stoykov I, Beattie SD, Kuo WL, Schiff M. Baricitinib, Methotrexate, or Baricitinib Plus Methotrexate in Patients with Early Rheumatoid Arthritis Who Had Received Limited or No Treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARDs): Phase 3 Trial Results [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/baricitinib-methotrexate-or-baricitinib-plus-methotrexate-in-patients-with-early-rheumatoid-arthritis-who-had-received-limited-or-no-treatment-with-disease-modifying-anti-rheumatic-drugs-dmards-p/. Accessed November 20, 2015.

Genovese MC, Kremer JM, Kartman C, Schlichting DE, Xie L, Carmack T, Macias WL, Smolen JS. Previous Biologic Disease-Modifying Antirheumatic Drug (bDMARD) Exposure and Efficacy and Safety Analysis from a Phase 3 Study of Baricitinib in Patients with Rheumatoid Arthritis and an Inadequate Response to Tumor Necrosis Factor Inhibitors [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/previous-biologic-disease-modifying-antirheumatic-drug-bdmard-exposure-and-efficacy-and-safety-analysis-from-a-phase-3-study-of-baricitinib-in-patients-with-rheumatoid-arthritis-and-an-inadequate-re/. Accessed November 20, 2015.

Emery P, McInnes I, Genovese MC, Smolen JS, Kremer J, Dougados M, Schlichting DE, Rooney T, Issa M, de Bono S, Macias WL, Rogai V, Zuckerman SH, Taylor PC. Characterization of Changes in Lymphocyte Subsets in Baricitinib-Treated Patients with Rheumatoid Arthritis in Two Phase 3 Studies [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/characterization-of-changes-in-lymphocyte-subsets-in-baricitinib-treated-patients-with-rheumatoid-arthritis-in-two-phase-3-studies/. Accessed November 20, 2015.

Emery P, McInnes I, Genovese MC, Smolen JS, Kremer J, Dougados M, Schlichting DE, Rooney T, Issa M, de Bono S, Macias WL, Rogai V, Zuckerman SH, Taylor PC. Characterization of Changes in Lymphocyte Subsets in Baricitinib-Treated Patients with Rheumatoid Arthritis in Two Phase 3 Studies [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/characterization-of-changes-in-lymphocyte-subsets-in-baricitinib-treated-patients-with-rheumatoid-arthritis-in-two-phase-3-studies/. Accessed November 20, 2015.

Kremer J, Dougados M, Genovese MC, Emery P, Yang L, de Bono S, Holzkaemper T, Iikuni N, Schlichting DE, Smolen JS. Response to Baricitinib at 4 Weeks Predicts Response at 12 and 24 Weeks in Patients with Rheumatoid Arthritis: Results from Two Phase 3 Studies [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/response-to-baricitinib-at-4-weeks-predicts-response-at-12-and-24-weeks-in-patients-with-rheumatoid-arthritis-results-from-two-phase-3-studies/. Accessed November 20, 2015.

Emery P, Gaich CL, DeLozier AM, de Bono S, Liu J, Chang C, Dougados M. Patient-Reported Outcomes from a Phase 3 Study of Baricitinib in Patients with Rheumatoid Arthritis with Inadequate Response to Conventional Synthetic Disease-Modifying Antirheumatic Drugs [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/patient-reported-outcomes-from-a-phase-3-study-of-baricitinib-in-patients-with-rheumatoid-arthritis-with-inadequate-response-to-conventional-synthetic-disease-modifying-antirheumatic-drugs/. Accessed November 20, 2015.

.