AB1309 Radiographic progression of weight-bearing large joint damage in patients with rheumatoid arthritis during tnf-blocking therapies – maximum 12-year follow up –

AbstractBaricitinib 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.

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MRI in early rheumatoid arthritis: synovitis and bone marrow oedema are independent predictors of subsequent radiographic progression

Annals of the Rheumatic Diseases ◽

10.1136/ard.2009.123950 ◽

2010 ◽

Vol 70 (3) ◽

pp. 428-433 ◽

Cited By ~ 88

Author(s):

Pernille Bøyesen ◽

Espen A Haavardsholm ◽

Mikkel Østergaard ◽

Désirée van der Heijde ◽

Sølve Sesseng ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Bone Marrow ◽

Early Rheumatoid Arthritis ◽

Radiographic Progression ◽

Bone Marrow Oedema ◽

Tender Joint Count ◽

X Rays ◽

Tender Joint ◽

Reactive Protein

ObjectivesTo determine whether MRI and conventional (clinical and laboratory) measures of inflammation can predict 3-year radiographic changes measured by the van der Heijde Sharp score in patients with early rheumatoid arthritis (RA).Methods55 patients with RA with disease duration <1 year participated in this 3-year follow-up study. Patients were evaluated at baseline, 3, 6, 12 and 36 months by swollen and tender joint count, disease activity score based on 28-joint count, erythrocyte sedimentation rate (ESR), C reactive protein, MRI measures of synovitis, bone marrow oedema and tenosynovitis of the dominant wrist, as well as conventional x-rays of the hands and wrists.ResultsAll measures of inflammation decreased during the follow-up period. ESR, MRI synovitis and MRI bone marrow oedema were independent predictors of 3-year radiographic progression adjusted for age, sex and anti-citrullinated protein antibodies. The 1-year cumulative measures of MRI synovitis and bone marrow oedema provided an improved explanation of variation (adjusted R2) in radiographic change compared with the baseline MRI values (adjusted R2=0.32 and 0.20 vs 0.11 and 0.04, respectively).ConclusionsBoth baseline and 1-year cumulative measures of MRI synovitis and bone marrow oedema independently predicted 3-year radiographic progression. These results confirm that MRI synovitis and MRI bone marrow oedema precede radiographic progression in patients with early RA.

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Understanding the Mechanisms of Pain in Rheumatoid Arthritis

Rheumatoid Arthritis - Other Perspectives towards a Better Practice ◽

10.5772/intechopen.93829 ◽

2020 ◽

Author(s):

Kathryn Biddle ◽

Nidhi Sofat

Keyword(s):

Rheumatoid Arthritis ◽

Joint Damage ◽

Joint Inflammation ◽

Long Term Follow Up ◽

Important Symptom ◽

Ongoing Pain ◽

Disease Modifying Agents

Pain is a debilitating feature of rheumatoid arthritis (RA) and is often described by patients as their most important symptom. Rheumatoid arthritis pain has traditionally been attributed solely to joint inflammation, however despite the advent of increasingly effective disease modifying agents, patients continue to report pain at long term follow up. The cause for ongoing pain is multifactorial and includes joint damage and pain sensitisation. In this book chapter, we will describe the mechanisms underlying the distinct components of pain which are manifest in rheumatoid arthritis and discuss why a thorough assessment of pain is vital to target treatments appropriately.

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Low rates of radiographic progression of structural joint damage over 2 years of baricitinib treatment in patients with rheumatoid arthritis

RMD Open ◽

10.1136/rmdopen-2019-000898 ◽

2019 ◽

Vol 5 (1) ◽

pp. e000898 ◽

Cited By ~ 5

Author(s):

Desirée van der Heijde ◽

Michael Schiff ◽

Yoshiya Tanaka ◽

Li Xie ◽

Gabriella Meszaros ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Combination Therapy ◽

Radiographic Progression ◽

Joint Damage ◽

Phase Iii ◽

Inadequate Response ◽

Smallest Detectable Change ◽

Structural Joint ◽

Synthetic Dmards ◽

Modified Total Sharp Score

ObjectivesTo evaluate radiographic progression of structural joint damage over 2 years in patients with rheumatoid arthritis from baricitinib clinical trials who were disease-modifying antirheumatic drug (DMARD)–naïve or had an inadequate response to conventional synthetic DMARDs (csDMARD-IR).MethodsPatients had completed one of three phase III studies and entered a long-term extension (LTE) study, continuing on the same baricitinib dose as at originating study completion. At 52 weeks, DMARD-naïve patients receiving methotrexate (MTX) or combination therapy (baricitinib 4 mg+MTX) were switched to baricitinib 4 mg monotherapy (±MTX per investigator opinion); MTX-IR patients receiving adalimumab were switched to baricitinib 4 mg on background MTX. At 24 weeks, csDMARD-IR patients receiving placebo were switched to baricitinib 4 mg on background csDMARD. Radiographs at baseline, year 1 and year 2 were scored using the van der Heijde modified Total Sharp Score. Linear extrapolation was used for missing data.ResultsOf 2573 randomised patients, 2125 (82.6%) entered the LTE, of whom 1893 (89.1%) entered this analysis. At year 2, progression was significantly lower with initial baricitinib (monotherapy or combination therapy) versus initial MTX in DMARD-naïve patients (proportion with non-progression defined by ≤smallest detectable change (SDC): 87.3% baricitinib 4 mg+MTX; 70.6% MTX; p≤ 0.001). In MTX-IR patients, progression with initial baricitinib was significantly lower than with initial placebo and similar to initial adalimumab (≤SDC: 82.7% baricitinib 4 mg; 83.5% adalimumab; 70.6% placebo; p≤0.001). In csDMARD-IR patients, significant benefit was seen with baricitinib 4 mg (≤SDC: 87.2% vs 73.2% placebo; p≤0.01).ConclusionsTreatment with once-daily baricitinib resulted in low rates of radiographic progression for up to 2 years.

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Effect on efficacy and safety trial outcomes of also enrolling patients on ongoing glucocorticoid therapy in rheumatoid arthritis clinical trials of tocilizumab or adalimumab or methotrexate monotherapy

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2019-216537 ◽

2020 ◽

Vol 79 (4) ◽

pp. 460-463 ◽

Cited By ~ 3

Author(s):

Mary Safy-Khan ◽

Johannes W G Jacobs ◽

Maria J H de Hair ◽

Paco M J Welsing ◽

Michael D Edwardes ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Trials ◽

Radiographic Progression ◽

Joint Damage ◽

Incidence Rates ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind ◽

Safety Outcomes ◽

Trial Outcomes

BackgroundIn rheumatoid arthritis (RA) trials, inclusion of patients on background treatment with glucocorticoids (GCs) might impact efficacy and safety outcomes.ObjectivesTo determine if inclusion of patients on background GC use influenced efficacy and safety outcomes of RA randomised clinical trials on initiation of tocilizumab (TCZ) or adalimumab (ADA) or methotrexate (MTX) monotherapy.MethodsData of four double-blind RA randomised controlled trials (AMBITION, ACT-RAY, ADACTA and FUNCTION) with in total four TCZ, one ADA and two MTX monotherapy arms were analysed. Analyses of covariance of changes from baseline to week 24 in efficacy endpoints and radiographic progression up to week 104 were performed, correcting for relevant covariates. Incidence rates of serious adverse events (SAEs) were assessed.ResultsNo statistically significant differences were found in efficacy parameters between background GC users and non-GC users, except for less radiographic progression associated with GC usage in one MTX arm. SAE rates were not statistically significantly different between GC users and non-GC users in the treatment arms.ConclusionNo effect of including patients on background GC treatment on efficacy and safety trial outcomes was found, with the exception of reduced radiological joint damage in one MTX arm.

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