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

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...

Efficacy of Monotherapy with Biologics and JAK inhibitors for the Treatment of Rheumatoid Arthritis: A Systematic Review

ADV Ther 2018; 35(10):1525–63 DOI: 10.1007/s12325-018-0757-2

Emery P,

Pope JE,

Kruger K,

Lippe R,

DeMasi R,

Lula S,

Kola B

The b/tsDMARDs evaluated in this systematic literature review (SLR) were shown to be efficacious as monotherapies, although combination therapies usually achieved better treatment outcomes.Current treatment guidelines recommend combining b/tsDMARDs with MTX in the treatment of RA; however, up to a third of patients are treated with monotherapy. While previous SLRs1–3 have compared the efficacy of b/tsDMARD mono- versus MTX combination therapy they covered a limited number of randomised controlle...

Keywords:

• JAK,
• Review

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

Evaluation of Disease Activity in Patients with Rheumatoid Arthritis Treated with Tofacitinib by RAPID3: Post Hoc Analyses from Two Phase 3 Trials

Clin Rheumatol 2018 Aug; 37(8):2043–53

Strand V,

Lee EB,

Yazici Y,

Dikranian A,

Wilkinson B,

Takiya L,

Zang C,

Bananis E,

Bergman MJ

Patients given tofacitinib (TOF) who achieved Routine Assessment of Patient Index Data 3 (RAPID3) remission or low disease activity (LDA) at 6 months, had improved long-term outcomes at 2 years, compared to patients with moderate or high disease activity (MDA/HDA) at 6 months.RAPID3¹ is a patient-reported evaluation of disease activity, based on pooled PROs; patient global assessment, patient assessment of arthritic pain and HAQ-DI scores. Previous studies with tocilizumab have suggested that RA...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3

Effectiveness and Safety of Tofacitinib in Rheumatoid Arthritis: a Cohort Study

Arthritis Res Ther 2018; 20(1):60 doi: 10.1186/s13075-018-1539-6

Machado MAÁ,

Moura CS,

Guerra SF,

Curtis JR,

Abrahamowicz M,

Bernatsky S

A retrospective cohort study of tofacitinib (TOF) revealed that patients previously treated with methotrexate who initiated TOF, presented no differences in hospitalised infections or effectiveness, compared with non-TNF biologics. Currently, TOF is recommended in ACR and EULAR guidelines as an alternative to biologics after first-line cDMARD therapy. Previous indirect comparisons have shown that patients with RA who experience cDMARD failure show similar efficacy when given TNFis, abatacept, to...

Keywords:

• JAK,
• Tofacitinib,
• Real-World

Radiographic Joint Damage in Early Rheumatoid Arthritis Patients: Comparing Tocilizumab- and Methotrexate-based Treat-to-target Strategies

Rheumatology (Oxford) 2018; 57(2):309–17

Teitsma X,

Jacobs JWG,

Welsing PMJ,

Pethӧ-Schramm A,

Borm MEA,

van Laar JM,

Lafeber FPJG,

Bijlsma JWJ

Tocilizumab (TCZ) therapy in DMARD-naïve patients with RA, is more effective at reducing erosion progression, particularly in the feet, compared with treat-to-target methotrexate (MTX) therapy. This analysis looked at radiographic joint damage, including separate examination of erosion progression and joint space narrowing (JSN) in the hands and feet of patients enrolled in the U-Act-Early trial. Radiographic damage is a common symptom of RA, with treat-to-target strategies aimed at preventing ...

Keywords:

• IL-6,
• Tocilizumab,
• Radiographic

Tapering versus Steady-state Methotrexate in Combination with Tocilizumab for Rheumatoid Arthritis: a Randomised, Double-blind Trial

Rheumatology (Oxford) 2018;57(1):84–91

Edwards CJ,

Ӧstӧr AJK,

Naisbett-Groet B,

Kiely P

Methotrexate (MTX) tapering in patients with active, severe RA receiving intravenous tocilizumab (TCZ) was non-inferior to continuing stable MTX doses in maintaining a good/moderate EULAR response. Although MTX and bDMARD combination therapy may produce better response rates than bDMARD monotherapy, one third of patients discontinue or are non-compliant with MTX due to preference or toxicity. This randomised, non-inferiority study investigated the efficacy and tolerability of MTX tapering and ma...

Professor Iain McInnes Reviews the Most Important Papers from 2017

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

McInnes I

2017 was a successful year for rheumatoid arthritis research, with some key advances in JAK inhibitors and IL-6 inhibitors, as outlined below. - Tofacitinib was suggested as a potential treatment for psoriatic arthritis, and NICE recommended tofacitinib as a treatment for moderate to severe rheumatoid arthritis - Baricitinib studies supported the potential use of baricitinib as a treatment for rheumatoid arthritis - Filgotinib Phase 2 studies suggested that filgotinib could be effective a...

Keywords:

• Review

Subcutaneous Tocilizumab in Rheumatoid Arthritis: Findings from the Common-framework Phase 4 Study Programme TOZURA Conducted in 22 Countries

Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. DOI: 10.1093/rheumatology/kex443

Choy E,

Caporali R,

Xavier R,

Fautrel B,

Sanmarti R,

Bao M,

Bernasconi C,

Pethö-Schramm A

This multi-national TOZURA study programme confirmed the efficacy and safety profile of subcutaneous tocilizumab (TC-SC) when administered as either monotherapy or in combination with csDMARDs. TOZURA was a Phase 4 study programme that evaluated open-label, TCZ-SC in patients with moderate-to-severe RA. A total of 1804 patients with active RA were enrolled in the study programme. Patients had inadequate responses to csDMARDs, anti-TNF therapies, or they were MTX-naïve. TCZ-SC was administered we...