Publications

EULAR Recommendations for the Management of Rheumatoid Arthritis – 2019 Update and Consensus Statement on JAKinibs

Ann Rheum Dis. 2020 Jan 22. pii: annrheumdis-2019-216655.

Smolen JS,

Landewé RBM,

Bijlsma JWJ,

Burmester GR,

Dougados M,

Kerschbaumer A,

McInnes IB,

Sepriano A,

et al.

The EULAR recommendations for the management of RA have become increasingly useful in providing rheumatologists, patients, payers and other stakeholders with the evidence-based guidance and views of experts on the optimal use and sequence of pharmaceutical therapies in patients with RA. Over the course of the last decade, the evolution of the treatment landscape has already required two updates. The release of the new addition updates the 2016 recommendations.An international task force consider...

Keywords:

• EULAR

A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis

Rheumatology (Oxford) 2019;58(10):1755–66

Bechman K,

Subesinghe S,

Norton S,

Atzeni F,

Galli M,

Cope AP,

Winthrop KL,

Galloway JB

Absolute serious infection rates were low. However, across the JAKinibs, the incidence of HZ is higher than expected for the population. While the risk was numerically greatest with BARI, indirect comparisons between the drugs did not demonstrate any significant difference in risk. How JAKinibs increase the risk of HZ reactivation is unclear, but how different JAKs interact in the immune response suggest that there may be differences in safety profiles between JAKinib drugs, underpinned by their...

Keywords:

• Safety,
• Review

Upadacitinib versus Placebo or Adalimumab in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase 3, Double-Blind, Randomized Controlled Trial

Arthritis Rheumatol 2019 DOI: 10.1002/art.41032

Fleischmann R,

Pangan AL,

Song IH,

Mysler E,

Bessette L,

Peterfy C,

Durez P,

Ostor AJ,

Li Y,

Zhou Y,

Othman AA,

Genovese MC

UPA demonstrated superiority to ADA in terms of clinical, functional and patient-reported outcomes with comparable radiographic inhibition. As many RA patients fail to achieve LDA and remission with TNF inhibitors and MTX there is a requirement for additional treatment options. In this SELECT-COMPARE study the clinical and functional outcomes of UPA were compared to ADA in MTX-IR patients. 1629 MTX-IR were randomly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W or PBO, with background MTX. Key end...

Keywords:

• JAK,
• Updacitinib,
• Phase 3

Safety and Effectiveness of Upadacitinib or Adalimumab Plus Methotrexate in Patients with Rheumatoid Arthritis Over 48 Weeks with Switch to Alternate Therapy in Patients with Insufficient Response

Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215764

Fleischmann RM,

Genovese MC,

 Enejosa JV,

 Mysler E,

Bessette L,

Peterfy C,

 Ostor P,

 Li Y,

 Song I

Consistent with Wk26 data, significantly more UPA patients achieved LDA and remission versus ADA and PBO over 48 weeks. RA patients often change therapy due to inadequate response and intolerance. The SELECT COMPARE study was designed to explore switching to JAK inhibitors from TNF inhibitors without a wash-out period (and vice versa). The long-term safety and efficacy of UPA was compared to ADA and PBO in MTX-IR.1629 patients were blindly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W and PBO, wi...

Keywords:

• JAK,
• Updacitinib,
• Phase 3

Safety and Efficacy of Tofacitinib For Up to 9.5 Years in The Treatment of Rheumatoid Arthritis: Final Results of a Global, Open-Label, Long-Term Extension Study

Arthritis Res Ther. 2019 Apr 5;21(1):89.

Wollenhaupt J,

Lee EB,

Curtis JR,

Silverfield J,

Terry K,

Soma K,

Mojcik C,

DeMasi R,

Strengholt S,

Kwok K,

Lazariciu I,

Wang L,

Cohen S

TOF 5 mg and 10mg BID demonstrated a consistent safety profile and sustained efficacy for up to 9.5 years in this open-label LTE ORAL Sequel study.TOF 5 mg and 10 mg BID demonstrated consistent safety (as monotherapy and combination therapy) and efficacy within this open-label LTE study of RA patients. As RA requires long-term treatment, it’s important to assess the long-term efficacy and safety of RA therapies to understand the potential lifelong impact on patient health and quality of life. Th...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Efficacy,
• LTE

Risk of Serious Infection in Patients with Rheumatoid Arthritis in Routine Care with Abatacept, Rituximab and Tocilizumab in Denmark and Sweden

Ann Rheum Dis. 2019 Mar;78(3):320-327. DOI: 10.1136/annrheumdis-2018-214326

Grøn KL,

Arkema EV,

Glintborg B,

Mehnert F,

Østergaard M,

Dreyer L,

Nørgaard M,

Krogh NS,

Askling J,

Hetland ML; ARTIS Study Group

Differences in baseline characteristics and numerical differences in IR of SI between ABA, RRTX and TOZ were observed. The relative risk (RR) of SIs seemed to vary modestly with drug.TNFi treated RA patients in large observational studies have suggested an initial twofold increased risk of SIs compared with biologic-naïve patients. Long-term observational studies on the risk of SIs in patients treated with non-TNFi bDMARDs are sparse.This study aimed to estimate crude as well as age and gender-a...

Keywords:

• Abatacept,
• Tocilizumab,
• Infections

Comparisons of Hepatitis C Viral Replication in Patients with Rheumatoid Arthritis Receiving Tocilizumab, Abatacept and Tofacitinib Therapy

Ann Rheum Dis. 2019 Jun;78(6):849-850.

Chen YM,

Huang WN,

Liao TL,

Chen JP,

Yang SS,

Chen HH,

Hsieh TY,

Hung WT,

Chen YH,

Chen DY

Tocilizumab (TCZ), abatacept (ABA) and tofacitinib (TOF) appear to have no major safety concerns for treatment of RA patients with hepatitis C virus (HCV) infections.HCV is an infectious disease which continues to present a major therapeutic challenge for clinicians in treating patients with RA. Previous reports demonstrate that the use of TNF targeted therapies in RA patients with HCV infections appear to have no major safety concerns. During short-term therapy with TCZ and ABA, data has shown ...

Keywords:

• Tofacitinib,
• Tocilizumab,
• Abatacept,
• Infections

Comparative Risk of Venous Thromboembolism with Tofacitinib versus Tumour Necrosis Factor Inhibitor: A Cohort study of Rheumatoid Arthritis Patients

Desai RJ, et al. Arthritis Rheumatol. 2019 June;71(6):892-900.

Desai RJ,

Pawar A,

Weinblatt ME,

Kim SC

Occurrences of venous thromboembolism (VTE) in 50, 865 RA patients initiating Tofacitinib (TOF) or a TNF inhibitor (TNFi) was infrequent. No significant risk of VTE for TOF versus TNFi was observed.Safety concerns of JAK inhibitor BARI include potentially increased risk of VTE at the higher 4 mg dose. It’s unclear if this is attributable to JAK-inhibition and extends to TOF. This study compared the risk of VTE with TOF, versus TNFi in real-world settings with RA patients.RA patients initiating T...

Keywords:

• JAK,
• Tofacitinib,
• Safety

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

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