Publications

Professor Iain McInnes Reviews the Most Notable Papers from 2018

Please click the links below to go to the CSF review of each paper

McInnes. I

2018 brought a wealth of new data in cytokine signalling and IL-6 that helps inform current clinical practice and brings the promise of new options in the future. There was good data on the use of sub cutaneous tocilizumab as well as strategies in early RA and for methotrexate tapering. For the currently marketed JAK inhibitors, tofacitinib and baricitinib, continuous long-term efficacy and safety data further support its current use and applications. On the development side, the outcomes of the...

Keywords:

• Review

Evaluation of the Short-, Mid-, and Long-term Effects of Tofacitinib on Lymphocytes in Patients with Rheumatoid Arthritis

Arthritis Rheumatol 2018 DOI: 10. 1002/art.40780

van Vollenhoven R,

Lee EB,

Strengholt S,

Mojcik C,

Valdez H,

Krishnaswami S,

Biswas P,

Lazariciu I,

Hazra A,

Clark JD,

Hodge J,

Wang L,

Choy E

Tofacitinib (TOF) treatment is associated with short-term transient increases in absolute lymphocyte counts (ALC), followed by a gradual decline to reach steady state by ~48 months. Changes in both ALC and lymphocyte subset counts (LSC) were reversible upon TOF discontinuation. Low ALC but not LSC were associated with an increased risk of serious infective episodes (SIEs) and herpes zoster (HZ). This data supported the treatment recommendations on ALC counts for starting and continuing therapy w...

Keywords:

• JAK,
• Tofacitinib,
• MOA

Safety and Efficacy of Baricitinib in Patients Receiving Conventional Synthetic Disease-Modifying Antirheumatic Drugs or Corticosteroids

Rheumatol Ther 2018 Dec;5(2):525-536. DOI 10.1007/s40744-018-0128-0

van Vollenhoven R,

Helt C,

Arora V,

Zhong J,

Correia AP,

de la Torre I,

Muram D

Baricitinib (BARI) in combination with MTX and concomitant csDMARDs was shown to be efficacious, regardless of corticosteroid use in RA patients. MTX is prescribed to most RA patients but concomitant csDMARDs and/or corticosteroids can be added. This study assessed the efficacy and safety of BARI in two arms; with/without corticosteroids and; with MTX only/MTX plus csDMARD/csDMARDs only. Baseline characteristics and adverse reactions were also compared. Data were pooled from two phase 3 studies ...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Efficacy

Dose Reduction of Baricitinib in Patients with Rheumatoid Arthritis Achieving Sustained Disease Control: Results of a Prospective Study

Ann Rheum Dis. 2019 Feb;78(2):171-178. DOI 10.1136/annrheumdis-2018-213271

Takeuchi T,

Genovese MC,

Haraoui B,

Li Z,

Xie L,

Klar R,

Pinto Correia A,

Otawa S,

Lopez-Romero P,

de la Torre I,

Rooney TP,

Smolen JS

In active RA patients, with an inadequate response (IR) to DMARDs who achieve low disease activity (LDA) following baricitinib (BARI) 4 mg treatment, disease control is better maintained with continued BARI 4 mg compared to tapering to 2 mg.The objective of this study was to investigate the effect of BARI tapering in patients achieving sustained disease control with BARI 4 mg.In the long-term extension study RA-BEYOND, patients receiving BARI 4 mg who achieved sustained LDA or remission at two c...

Keywords:

• JAK,
• Baricitinib

Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis with over 2 Years Median Time in Treatment

J Rheumatol. 2019 Jan;46(1):7-18. DOI: 10.3899/jrheum.171361

Smolen J,

Genovese M,

Takeuchi T,

Hyslop D,

Macias W,

Rooney T,

Chen L,

Dickson C,

Riddle Camp J,

Cardillo T,

Ishii T and Winthrop K

Baricitinib (BARI) showed an acceptable 5.5-year safety profile in this integrated analysis of patients with moderate-to-severe, active RA.This study evaluated the safety profile of the oral, once daily Janus kinase inhibitor, BARI, in adults with moderately to severely active RA. Data from eight randomised clinical trials and one long-term extension study were pooled and analysed for placebo comparison and dose response.There were 3492 patients who received BARI for a total of 6637 patient-yea...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Review

Sustained Response Following Discontinuation of Methotrexate in Patients with Rheumatoid Arthritis Treated with Subcutaneous Tocilizumab

Arthritis Rheumatol 2018;70:1200–08 DOI 10.1002/art.40493

Kremer JM,

Rigby W,

Singer NG,

Birchwood C,

Gill D,

Reiss W,

Pei J,

Michalska M

The COMP-ACT study showed patients achieving low disease activity (LDA) with tocilizumab (TCZ) plus methotrexate (MTX) can discontinue MTX, while maintaining disease control for up to 16 weeks.Previous studies have shown TCZ to be efficacious as a monotherapy or in combination with MTX in patients with RA1,2. Patients frequently discontinue taking DMARDs, such as MTX, due to intolerance or adverse events.COMP-ACT is a randomised, double-blind, 52-week study evaluating the sustained efficacy of s...

Tocilizumab Discontinuation After Attaining Remission in Patients with Rheumatoid Arthritis who were Treated with Tocilizumab Alone or in Combination with Methotrexate: Results from a Prospective Randomised Controlled Study (the second year of the SURPRISE study)

Ann Rheum Dis 2018; 77:1268–1275 DOI: 10.1093/rheumatology/key121

Kaneko Y,

Kato M,

Tanaka Y,

Inoo M,

Kobayashi-Haraoka H,

Amano K,

Miyata M,

Murakawa Y,

Yasuoka H,

Hirata S,

Tanaka E,

Miyasaka N,

Yamanaka H,

Yamamoto K,

Takeuchi T,

the SURPRISE study group

The second-year results from the SURPRISE study show that low disease activity (LDA) can be maintained after discontinuation of tocilizumab with continued methotrexate after remission is achieved. Discontinuation of biologic agents in patients who have achieved remission or low disease activity (LDA) is desirable from a risk–benefit point of view. Compared with TNF inhibitors, little is known regarding TCZ-free remission or LDA, but studies indicate that only a small proportion of patients remai...

Keywords:

• IL-12,
• Tocilizumab,
• Phase 3,
• Persistence

Two Years of Sarilumab in Patients with Rheumatoid Arthritis and an Inadequate Response to MTX: Safety, Efficacy and Radiographic Outcomes

Rheumatology 2018;57:1423–1431 DOI: 10.1093/rheumatology/key121

Genovese MC,

van Adelsberg J,

Fan C,

Graham NMH,

van Hoogstraten H,

Parrino J,

Mangan EK,

Spindler A,

Huizinga TWJ,

van der Heijde D,

for the EXTEND study investigators

Two-year treatment of active, moderate-to-severe RA with sarilumab, along with dose reduction in the event of laboratory abnormalities, resulted in durable efficacy outcomes and a safety profile consistent with previous reports involving IL-6R inhibition. Durable long-term safety and efficacy, reduced joint damage progression, and conserving health-related quality of life and work productivity are important goals of therapy in RA.1 Sarilumab significantly reduced disease activity, improved physi...

Keywords:

• IL-6,
• Sarilumab,
• Phase 3,
• Safety,
• Radiographic

Safety and Efficacy of Upadacitinib in Patients with Rheumatoid Arthritis and Inadequate Response to Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (SELECT-NEXT): a Randomised, Double-Blind, Placebo-Controlled Phase 3 Trial

Lancet 2018;391:2503–12

Burmester GR,

Kremer JM,

Van den Bosch F,

Kivitz A,

Bessette L,

Li Y,

Zhou Y,

Othman AA,

Pangan AL,

Camp HS

Patients with moderate-to-severe active RA had significant improvements in clinical signs and symptoms with upadacitinib (UPA) compared with placebo.In Phase 2 studies, UPA showed favourable efficacy when administered twice daily as an immediate-release formulation at doses of 6–12 mg in patients with active RA who had TNFi-IR.1,2 An extended-release formulation allowing once-daily (QD) administration was developed for Phase 3 studies. SELECT-NEXT was a double-blind, multicentre, Phase 3 study t...

Keywords:

• JAK,
• Updacitinib,
• Phase 3

Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis

Rheumatol Ther 2018 Jun; 5(1):203–14. DOI: 10.1007/s40744-018-0093-7

Fleischmann R,

Wollenhaupt J,

Cohen S,

Wang L,

Fan H,

Bandi V,

Andrews J,

Takiya L,

Bananis E,

Weinblatt ME

Methotrexate (MTX) or Glucocorticoid (GC) discontinuation has little effect on CDAI response in patients given tofacitinib (TOF) for up to 3 years. Patients receiving TOF who showed initial improvements benefitted from initiation of MTX or GCs. Concomitant treatments such as MTX or GC are commonly used in combination with RA therapies to improve or accelerate clinical responses. However, their use is associated with many adverse events so clinicians aim to use them for a minimal duration.This po...

Keywords:

• JAK,
• Tofacitinib