Publications

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

A Pooled analysis of the Safety of Tofacitinib as Monotherapy or in Combination with Background Conventional Synthetic Disease-Modifying Antirheumatic Drugs in a Phase 3 Rheumatoid Arthritis Population

Semin Arthritis Rheum. 2018 Dec;48(3):406-415. doi: 10.1016/j.semarthrit.2018.07.006.

Kivitz AJ,

Cohen S,

Keystone E,

van Vollenhoven RF,

Haraoui B,

Kaine J,

Fan H,

Connell CA,

Bananis E,

Takiya L,

Fleischmann R

In this pooled analysis of Phase 3 Tofacitinib (TOF) trials, safety profiles were generally similar between patients receiving monotherapy and combination therapy. Although selected adverse events of interest showed lower incidence rates (IRs) for TOF monotherapy patients.TOF has been studied as monotherapy and in combination with csDMARDs. In this post-hoc analysis, data were pooled from six Phase 3 TOF studies in RA patients to further examine the safety profile when used as monotherapy or in ...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• Meta analysis

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

Lipid Profile and Effect of Statin Treatment in Pooled Phase II and Phase III Baricitinib Studies

Ann Rheum Dis. 2018 Jul;77(7):988-995. DOI 10.1136/annrheumdis-2017-212461

Taylor PC,

Kremer JM,

Emery P,

Zuckerman SH,

Ruotolo G,

Zhong J,

Chen L,

Witt S,

Saifan C,

Kurzawa M,

Otvos JD,

Connelly MA,

Macias WL,

Schlichting DE,

Rooney TP,

de Bono S,

McInnes IB

Baricitinib (BARI) was associated with increased lipid levels; baseline statins did not alter these profiles. The introduction of statins during treatment reduced total cholesterol and LDL-C.The use of anti-inflammatory drugs in RA patients has been shown to alter lipid levels and is associated with reduced atherogenic risk. Increases in lipid levels, specifically HDL-C and LDL-C, have been observed in Phase 2 BARI studies1.This study analysed data from seven randomised RA Phase 2/3 studies of ...

Keywords:

• JAK,
• Baricitinib,
• Phase 3,
• Safety,
• Cardiovascular

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

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,
• Upadacitinib,
• Phase 3

Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity Predicts a Low Probability of Achieving Low Disease Activity at Month 6

Arthritis Care Res (Hoboken) 2019 Jan;71(1):71-79. DOI: 10.1002/acr.23585

Van Vollenhoven RF,

Lee EB,

Fallon L,

Zwillich SH,

Wilkinson B,

Chapman D,

Demasi R,

Keystone E

This post-hoc analysis of two, Phase 3 studies, ORAL Start and ORAL Standard shows that early treatment response can predict long-term disease activity outcomes. EULAR recommendations suggest that treat-to-target strategies require regular target assessments with treatment approaches changed if targets are not reached at 6 months. To optimize this strategy, therapy outcomes should be known, and the relationship between short and long-term outcomes defined. The current analysis focused on the dis...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3