Characteristics of patients initiating treatment with baricitinib and outcomes at follow-up: analysis of BSRBR-RA Registry data.

OBJECTIVES: To describe selected baseline characteristics, continuation with baricitinib and disease activity over time in patients initiating treatment with baricitinib in a UK real-world rheumatology setting. METHODS: Baseline and follow-up data were analysed from baricitinib-treated patients newly recruited to the British Society for Rheumatology Biologics Registry-RA (BSRBR-RA) baricitinib cohort between 1 January 2018 and 31 March 2020. The primary objective was to evaluate continuation of baricitinib treatment in patients with at least one follow-up. Analyses were performed using the full baricitinib cohort, overall and by patient subgroup: biologic DMARD (bDMARD)/targeted synthetic (ts)DMARD-naive vs -experienced, baricitinib 4 vs 2 mg, age ≥65 vs <65 years, monotherapy vs combination therapy and male vs female. RESULTS: At baseline, the study cohort (n = 561) was 76.5% female, mean age 60.0 years, had longstanding (mean 13.1 years) and severe RA, and 54.0% had previously received a bDMARD/tsDMARD. Of 265 and 110 patients completing the 6- and 12-month follow-ups with available data, 77.7 and 69.1% remained on baricitinib at each time, respectively. In all Kaplan-Meier analyses, >60% of patients remained on baricitinib at 540 days. Continuation of baricitinib therapy differed between some subgroup pairs (bDMARD/tsDMARD naive/experienced, baricitinib 2 mg/4 mg). Disease activity was lower at both follow-ups than at baseline, overall and in all subgroups. CONCLUSION: In the early years of real-world baricitinib use in the UK, a high proportion of patients continued with treatment at both 6 and 12 months, at which times disease activity was lower than at baseline.

Baricitinib inhibits structural joint damage progression in patients with rheumatoid arthritis-a comprehensive review.

Baricitinib is an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 that has proved effective and well tolerated in the treatment of rheumatoid arthritis (RA) in an extensive programme of clinical studies of patients with moderate-to-severe disease. In a phase 2b dose-ranging study of baricitinib in combination with traditional disease-modifying antirheumatic drugs (DMARDs) in RA patients, magnetic resonance imaging showed that baricitinib 2 mg or 4 mg once daily provided dose-dependent suppression of synovitis, osteitis, erosion and cartilage loss at weeks 12 and 24 versus placebo. These findings correlated with clinical outcomes and were confirmed in three phase 3 studies (RA-BEGIN, RA-BEAM and RA-BUILD) using X-rays to assess structural joint damage. In patients naïve to DMARDs (RA-BEGIN study), baricitinib 4 mg once daily as monotherapy or combined with methotrexate produced smaller mean changes in structural joint damage than methotrexate monotherapy at week 24. Differences versus methotrexate were statistically significant for combined therapy. In patients responding inadequately to methotrexate (RA-BEAM study), baricitinib 4 mg plus background methotrexate significantly inhibited structural joint damage at week 24 versus placebo, and the results were comparable to those observed with adalimumab plus background methotrexate. In patients responding inadequately to conventional synthetic DMARDs (csDMARDs; RA-BUILD study), baricitinib 4 mg again significantly inhibited radiographic progression compared with placebo at week 24. Benefits were also observed with baricitinib 2 mg once daily, but the effects of baricitinib 4 mg were more robust. The positive effects of baricitinib 4 mg on radiographic progression continued over 1 and 2 years in the long-term extension study RA-BEYOND, with similar effects to adalimumab and significantly greater effects than placebo. Findings from the phase 3 studies of patients with RA were supported by preclinical studies, which showed that baricitinib has an osteoprotective effect, increasing mineralisation in bone-forming cells. In conclusion, baricitinib 4 mg once daily inhibits radiographic joint damage progression in patients with moderate-to-severe RA who are naïve to DMARDs or respond inadequately to csDMARDs, including methotrexate, and the beneficial effects are similar to those observed with adalimumab.

Full dose, reduced dose or discontinuation of etanercept in rheumatoid arthritis.

BACKGROUND: The aim of the Dose Reduction or Discontinuation of Etanercept in Methotrexate-Treated Rheumatoid Arthritis Patients Who Have Achieved a Stable Low Disease Activity-State study was to investigate the effect of etanercept (ETN) dose maintenance, reduction or withdrawal on patients with rheumatoid arthritis (RA) who had already achieved stable low disease activity (LDA) on ETN 50 mg+methotrexate (MTX). METHODS: Patients with RA (n=91) and stable LDA with ETN 50 mg once weekly (QW)+MTX were included. After 8 weeks with unchanged treatment, 73 patients were randomised in a double-blind design to ETN 50 mg QW+MTX (ETN50), ETN 25 mg QW+MTX (ETN25) or placebo QW+MTX (PBO) for 48 weeks. Patients who flared were declared failures and treated with open-label ETN50 until week 48. The primary outcome was the proportion of patients on ETN50 versus PBO who were non-failures after 48 weeks. RESULTS: The proportion of non-failure patients was significantly lower with ETN50 (52%; p=0.007) and ETN25 (44%; p=0.044) versus PBO (13%). Median time to failure was significantly shorter with PBO (6 weeks) compared with ETN50 (48 weeks; p=0.001) and ETN25 (36 weeks; p<0.001). The majority of patients who flared regained LDA with open-label ETN50 quickly. Adverse events were consistent with the known side effect profiles of these medications. CONCLUSIONS: In patients with established RA who have achieved stable LDA on ETN50+MTX, continuing both is superior to PBO+MTX. Reduced dose ETN was also more effective than PBO in maintaining a favourable response, suggesting that a maintenance strategy with reduced dose ETN may be possible in a number of patients with established RA. TRIAL REGISTRATION NUMBER: NCT00858780.

Corticosteroids--from an idea to clinical use.

Corticosteroids form the basis of treatment in many inflammatory rheumatic diseases, both as systemic treatment and as treatment with local injections to reduce inflammation. In 1948 the first systemic treatment of a patient with a rheumatic disease was given to a woman with severe rheumatoid arthritis (RA); the impressive effect in this patient, and in another 15 patients, was reported by Dr Hench and co-workers in 1949. Systemic corticosteroid treatment was rapidly adopted and used not only for patients with RA but also for those with other rheumatic diseases such as systemic lupus erythematosus-as well as other disorders such as asthma-with a similar positive effect. In the following year, 1950, the Nobel Prize was awarded for the discovery of the structure and biological effects of the adrenal cortex hormones. This open trial was followed by several controlled trials conducted in the UK in which the effects of cortisone were compared with the effects of aspirin in patients with RA-interestingly, without any significant clinical benefit for the cortisone-treated patients. It was not until 1959, in yet another multi-centre trial in Britain, that a significant effect on functional capacity and general well-being was reported after 2 years of treatment with prednisolone, compared to aspirin, in patients with early RA. Despite the dramatic effects that were observed in the severely ill RA patients reported by Hench and co-workers it took 10 years to demonstrate that this effect was superior to the effect of aspirin when the two compounds were compared in controlled trials. Why was this so? One explanation could be in the study designs and the different outcome measures used in the various studies. Perhaps the results in the first comparative studies would have been different if individual response criteria had been used. This is discussed in this chapter.