March 2018

Response to Baricitinib based on Prior Biologic Use in Patients with Refractory Arthritis

Rheumatology (Oxford) 2018 May; 57(5):900-908

Baricitinib (BARI) 2 or 4 mg had a beneficial treatment effect on patients with moderate to severe RA compared with placebo (PBO), irrespective of the number or nature of prior patient bDMARD use. The current therapeutic target for patients with established RA is low disease activity, but many patients fail to achieve this due to inadequate responses to DMARD therapies. With this patient population growing, therapies for these patients are considered one of the greatest unmet needs in RA. This s...

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February 2018

Tofacitinib with Conventional Synthetic Disease-modifying Antirheumatic Drugs in Chinese Patients with Rheumatoid Arthritis: Patient-reported Outcomes from a Phase 3 Randomised Controlled Trial

Int J Rheum Dis 2018; 21(2):402–14

This Chinese sub-population of patients with RA from ORAL Sync reported significant improvements in patient-reported outcomes (PROs), which were maintained up to 12 months from tofacitinib (TOF) treatment initiation. ORAL Sync was a randomised, Phase 3 study investigating TOF therapy in combination with csDMARDs in patients with active RA who had previously had an inadequate response to csDMARDs. To date, this is the only Phase 3 study of TOF in patients from China with RA. This analysis include...

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Professor Iain McInnes Reviews the Most Important Papers from 2017

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

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...

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December 2017

Effect of Glucocorticoids on the Clinical and Radiographic Efficacy of Tofacitinib in Patients with Rheumatoid Arthritis: A Posthoc Analysis of Data from 6 Phase III studies

J Rheumatol 2018 Feb; 45(2):177-87

In this post hoc analysis, six Phase 3 studies were used to analyse the effect of glucocorticoids (GC) on the efficacy of tofacitinib (TOF) in patients with RA. Concomitant use of GC did not affect the clinical or radiographic outcomes of patients treated with TOF. Data from all six clinical trials were evaluated, with four studies (ORAL Scan, ORAL Standard, ORAL Sync and ORAL Step) being pooled for analysis. In these studies, MTX was used as a comparison and patients were required to maintain a...

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JAK Inhibition as a Therapeutic Strategy for Immune and Inflammatory Diseases

Nat Rev Drug Discov 2017;16:843–62 DOI: 10.1038/nrd.2017.201

Janus kinases (JAKs) are essential mediators of downstream signaling pathways in many inflammatory and autoimmune diseases. This review summarizes current clinical data on first- and second-generation JAK inhibitors (jakinibs) and discusses their use for the treatment of immune and inflammatory conditions.First generation jakinibs such as tofacitinib, baricitinib, and ruxolitinib, non-selectively inhibit JAK-dependent pro-inflammatory cytokines, which are major contributors to immunopathology. T...

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Tofacitinib Therapy for Rheumatoid Arthritis: A Direct Comparison Study between Biologic-naive and Experienced Patients

Intern Med. 2018 Mar 1;57(5):663-670. doi: 10.2169/internalmedicine.9341-17

This 6-month prospective direct comparison study analysed the effectiveness of tofacitinib (TOF) therapy on bDMARD-naïve and bDMARD-experienced patients. bDMARD-naïve patients were more responsive to TOF therapy than bDMARD-experienced patients.The study analysed the data of 113 patients diagnosed with high or moderate disease activity, defined using CDAI scores. All patients had failed to achieve CDAI low disease activity or remission with MTX therapy for ≥3 months. Patients were given 5 mg TOF...

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November 2017

Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy

Arthritis Rheumatol 2017;69(10):1960–68

The results of this analysis of patients with herpes zoster (HZ) within the global tofacitinib (TOF) RA programme suggest that there is likely to be a greater HZ risk in patients receiving TOF and glucocorticoids compared with patients receiving TOF monotherapy.The global TOF RA development programme comprised 2 Phase 1, 9 Phase 2, 6 Phase 3 and 2 long-term extension studies. These studies included 6192 patients; data were reviewed to identify cases of HZ. Crude incidence rates of number of pati...

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Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis

N Engl J Med 2017; 377:1537-50. DOI: 10.1056/NEJMoa1615975

In the Phase 3 OPAL Broaden trial of patients with active psoriatic arthritis (PsA) with inadequate response to ≥1 csDMARD, superior efficacy was observed in patients treated with tofacitinib (TOF) compared with those given placebo. Patients were randomised to: 5 mg TOF BID, 10 mg TOF BID, 40 mg adalimumab administered subcutaneously q2W, or placebo with a switch to 5 mg TOF at Month 3. Adalimumab was used as an active control in the study. A variety of primary and secondary endpoints were used ...

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Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors

N Engl J Med 2017;377:1525–36.

The study data presented that tofacitinib (TOF) improves efficacy response rates in patients with severe psoriatic arthritis (PsA) who have an inadequate response to TNF inhibitors.The Phase 3 Oral Psoriatic Arthritis Trial (OPAL) Beyond study evaluated patients with active PsA who had inadequate responses to more than one TNFi. Patients were randomised 2:2:1:1 to 5 mg TOF BID or 10 mg TOF BID for 6 months; or PBO, with a switch to 5 mg TOF BID or to 10 mg BID at 3 months.Primary endpoints were ...

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Safety and Efficacy of Baricitinib in Elderly Patients with Rheumatoid Arthritis

RMD Open. 2017; 3(2): e000546. doi: 10.1136/rmdopen-2017-000546

In this post hoc analysis of pooled data from two randomised controlled trials, RA-BUILD and RA-BEAM, age was shown not to be a contraindication for use of baricitinib. Patients in RA-BUILD were csDMARD-inadequate responder(IR) patients who received an oral placebo or 2 mg or 4 mg baricitinib once daily. Patients in RA-BEAM were MTX-IR patients and received an oral placebo, 4 mg baricitinib once daily or subcutaneous adalimumab every 2 weeks. Efficacy and safety of baricitinib in elderly patient...

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