Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study

2017 ◽  
Vol 77 (1) ◽  
pp. 111-118 ◽  
Author(s):  
Gülşah Akdemir ◽  
Lotte Heimans ◽  
Sytske Anne Bergstra ◽  
Robbert J Goekoop ◽  
Maikel van Oosterhout ◽  
...  
Keyword(s):  
Functional Ability ◽  
Health Assessment ◽  
Joint Damage ◽  
Early Arthritis ◽  
Remission Induction ◽  
Treatment Groups ◽  
Damage Progression ◽  
Normal Functional ◽  
Radiological Damage ◽  
Drug Free

ObjectivesTo determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis.MethodsIn 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years.ResultsAfter 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR.Overall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0–2.7) Sharp/van der Heijde points, with only five patients showing progression >25 points in 5 years.ConclusionsFive years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal.

The impact of four dynamic, goal-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study

2011 ◽  
Vol 70 (6) ◽  
pp. 1039-1046 ◽  
Author(s):  
Naomi B Klarenbeek ◽  
Melek Güler-Yüksel ◽  
Sjoerd M van der Kooij ◽  
K Huub Han ◽  
H Karel Ronday ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Functional Ability ◽  
Joint Damage ◽  
Treatment Strategies ◽  
Recent Onset ◽  
Initial Combination Therapy ◽  
Dynamic Treatment ◽  
Drug Free ◽  
Initial Combination

ObjectiveTo compare clinical and radiological outcomes of four dynamic treatment strategies in recent-onset rheumatoid arthritis (RA) after 5 years follow-up.Methods508 patients with recent-onset RA were randomly assigned into four treatment strategies: sequential monotherapy; step-up combination therapy; initial combination with prednisone; initial combination with infliximab. Treatment adjustments were made based on 3-monthly disease activity score (DAS) measurements (if DAS >2.4 next treatment step; if DAS ≤2.4 during ≥6 months taper to maintenance dose; if DAS <1.6 during ≥6 months stop antirheumatic treatment). Primary and secondary outcomes were functional ability, joint damage progression, health-related quality of life and (drug-free) remission percentages.ResultsAfter 5 years, 48% of patients were in clinical remission (DAS <1.6) and 14% in drug-free remission, irrespective of initial treatment. After an earlier improvement in functional ability and quality of life with initial combination therapy, from 1 year onwards clinical outcomes were comparable across the groups and stable during 5 years. The initial combination groups showed less joint damage in year 1. In years 2–5 annual progression was comparable across the groups. After 5 years, initial combination therapy resulted in significantly less joint damage progression, reflecting the earlier clinical response.ConclusionIrrespective of initial treatment, an impressive improvement in clinical and radiological outcomes of RA patients can be achieved with dynamic treatment aimed at reducing disease activity, leading to 48% remission, 14% drug-free remission and sustained functional improvement. Starting with combination therapy resulted in earlier clinical improvement and less joint damage without more toxicity.

scholarly journals Baricitinib inhibits structural joint damage progression in patients with rheumatoid arthritis—a comprehensive review

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Paul Emery ◽  
Patrick Durez ◽  
Axel J. Hueber ◽  
Inmaculada de la Torre ◽  
Esbjörn Larsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Janus Kinase ◽  
X Rays ◽  
Phase 3 ◽  
Once Daily ◽  
Positive Effects ◽  
Damage Progression ◽  
Structural Joint

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.

scholarly journals MRI and Dose Selection in a Phase II Trial of Baricitinib with Conventional Synthetic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis

2019 ◽  
Vol 46 (8) ◽  
pp. 887-895 ◽  
Author(s):  
Charles Peterfy ◽  
Julie DiCarlo ◽  
Paul Emery ◽  
Mark C. Genovese ◽  
Edward C. Keystone ◽  
...  
Keyword(s):  
Bone Erosion ◽  
Joint Damage ◽  
Phase Iii ◽  
Cartilage Loss ◽  
Dose Selection ◽  
Mri Findings ◽  
Clinical Trial Registration ◽  
Treatment Groups ◽  
Link Type ◽  
Registration Number

Objective.Magnetic resonance imaging (MRI) was used in a phase IIb study of baricitinib in patients with RA to support dose selection for the phase III program.Methods.Three hundred one patients with active RA who were taking stable methotrexate were randomized 2:1:1:1:1 to placebo or once-daily baricitinib (1, 2, 4, or 8 mg) for up to 24 weeks. One hundred fifty-four patients with definitive radiographic erosion had MRI of the hand/wrist at baseline and at weeks 12 and 24. Two expert radiologists, blinded to treatment and visit order, scored images for synovitis, osteitis, bone erosion, and cartilage loss. Combined inflammation (osteitis + 3× synovitis score) and total joint damage (erosion + 2.5× cartilage loss score) scores were calculated. Treatment groups were compared using ANCOVA adjusting for baseline scores.Results.Mean changes from baseline to Week 12 for synovitis were −0.10, −1.50, and −1.60 for patients treated with placebo, baricitinib 4 mg, and baricitinib 8 mg, respectively (p = 0.003 vs placebo for baricitinib 4 and 8 mg). Mean changes for osteitis were 0.00, −3.20, and −2.10 (p = 0.001 vs placebo for baricitinib 4 mg and p = 0.037 for 8 mg), respectively. Mean changes for bone erosion were 0.90, 0.10, and 0.40 (p = 0.089 for 4 mg and p = 0.275 for 8 mg), respectively, in these treatment groups.Conclusion.MRI findings in this subgroup of patients suggest suppression of synovitis, osteitis, and combined inflammation by baricitinib 4 and 8 mg. This corroborates previously demonstrated clinical efficacy of baricitinib and increases confidence that baricitinib 4 mg could reduce the radiographic progression in phase III studies. [Clinical trial registration number (www.ClinicalTrials.gov): NCT01185353]

scholarly journals Health-related quality of life and functional ability in patients with early arthritis during remission steered treatment: results of the IMPROVED study

2013 ◽  
Vol 15 (5) ◽  
pp. R173 ◽  
Author(s):  
Lotte Heimans ◽  
Kirsten VC Boer ◽  
KK Koudijs ◽  
Karen Visser ◽  
Yvonne P Goekoop-Ruiterman ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Functional Ability ◽  
Early Arthritis ◽  
Health Related Quality ◽  
Treatment Results ◽  
Related Quality ◽  
Health Related

Role of joint damage, malalignment and inflammation in articular tenderness in rheumatoid arthritis, psoriatic arthritis and osteoarthritis

2021 ◽  
pp. annrheumdis-2020-218744
Author(s):  
Irina Gessl ◽  
Mihaela Popescu ◽  
Victoria Schimpl ◽  
Gabriela Supp ◽  
Thomas Deimel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Power Doppler ◽  
Joint Damage ◽  
Joint Space ◽  
Early Arthritis ◽  
Damage Score ◽  
Established Disease ◽  
Active Inflammation

ObjectivesTo determine whether clinical tenderness can be considered a sign of inflammatory joint activity in patients with rheumatoid arthritis (RA), osteoarthritis (OA) or psoriatic arthritis (PsA) and to assess other possible factors associated with tenderness.MethodsPatients diagnosed with RA, PsA and OA underwent clinical and ultrasound examination of wrists and finger joints. Radiographs of the hands were scored for erosions, joint space narrowing (JSN), osteophytes and malalignment. A binary damage score (positive if ≥1 erosion, JSN and/or presence of malalignment) was calculated. Differences in grey scale signs of synovitis and power Doppler (PD) between tender non-swollen (TNS) versus non-tender non-swollen (NTNS) joints were calculated. Disease duration was assessed,<2 years was regarded as early and >5 years as long-standing arthritis.ResultsIn total, 34 patients (9 early and 14 long-standing) from patients with RA, 31 patients (7 early and 15 long-standing) with PsA and 30 with OA were included. We found equal frequencies of PD signal between TNS and NTNS joints in RA (p=0.18), PsA (p=0.59) or OA (p=0.96). However, PD had a significant association with tenderness in early arthritis both in RA (p=0.02) and in PsA (p=0.02). The radiographic damage score showed significant association with tenderness in RA (p<0.01), PsA (p<0.01) and OA (p=0.04).ConclusionTenderness might not always be a sign of active inflammation in RA, PsA and OA. While tenderness in early arthritis may be more related to inflammation, established disease is better explained by joint damage and malalignment.

Clinical analysis of blood markers and imaging for diagnosis and prognosis of rheumatoid arthritis

2020 ◽  
Author(s):  
Desheng Yang ◽  
Haini Li ◽  
Shengxia Zhang ◽  
Guifeng Yang ◽  
Song Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Characteristic Curve ◽  
Joint Damage ◽  
Diagnostic Value ◽  
Clinical Analysis ◽  
Radiological Outcome ◽  
Diagnostic Efficacy ◽  
Diagnosis And Prognosis ◽  
Imaging Result ◽  
Radiological Damage

Abstract Background The purpose of this study is to explore the combined diagnostic value of anti-cyclic citrullinated peptide antibody (A-CCP), rheumatoid factor (RF) and imaging result in early rheumatoid arthritis, and the role of A-CCP and RF in prediction for radiological outcomes. Methods 101 patients with rheumatoid arthritis and 97 control individuals were detect their A-CCP, RF and radiological joint changes, the diagnostic efficacy of the respective indicators and the combined indicators was analyzed by logistic regression model. Results Our results showed that values of A-CCP and RF were significantly higher in the RA group than in the normal group. Receiver operating characteristic curve results show that the sensitivity of RF is higher than A-CCP and radiological outcome, and specificity of CCP is higher than RA and radiological outcome, and the diagnostic ability of combination of RF, A-CCP and radiological outcome is the strongest. Furthermore, RF and A-CCP had high significant OR for radiological joint damage and progression. Conclusions Our study indicated that the combined diagnosis of RF and A-CCP with radiological outcome can improve the diagnostic efficacy of RA, and RF and A-CCP are independent predictors of radiological damage and progression.

scholarly journals Synovitis in rheumatoid arthritis detected by grey scale ultrasound predicts the development of erosions over the next three years

Rheumatology ◽  
2019 ◽  
Vol 59 (7) ◽  
pp. 1556-1565 ◽  
Author(s):  
Burkhard Möller ◽  
Daniel Aletaha ◽  
Michael Andor ◽  
Andrew Atkinson ◽  
Bérengère Aubry-Rozier ◽  
...  
Keyword(s):  
Disease Activity ◽  
Joint Damage ◽  
Clinical Disease ◽  
Biological Dmards ◽  
Clinical Disease Activity ◽  
Upper Limit ◽  
Grey Scale ◽  
Damage Progression ◽  
Activity Measures ◽  
Disease Activity Measures

Abstract Objectives To evaluate grey scale US (GSUS) and power Doppler US synovitis (PDUS), separately or in combination (CombUS), to predict joint damage progression in RA. Methods In this cohort study nested in the Swiss RA register, all patients with sequential hand radiographs at their first US assessment were included. We analysed the summations of semi-quantitative GSUS, PDUS and CombUS assessments of both wrists and 16 finger joints (maximum 54 points) at their upper limit of normal, their 50th, 75th or 87.5th percentiles for the progression of joint damage (ΔXray). We adjusted for clinical disease activity measures at baseline, the use of biological DMARDs and other confounders. Results After a median of 35 months, 69 of 250 patients with CombUS (28%), 73 of 259 patients with PDUS (28%) and 75 of 287 patients with available GSUS data (26%) demonstrated joint damage progression. PDUS beyond upper limit of normal (1/54), GSUS and CombUS each at their 50th (9/54 and 10/54) and their 75th percentiles (14/54 and 15/54) were significantly associated with ΔXray in crude and adjusted models. In subgroup analyses, GSUS beyond 14/54 and CombUS higher than 15/54 remained significantly associated with ΔXray in patients on biological DMARDs, while clinical disease activity measures had no significant prognostic power in this subgroup. Conclusion Higher levels of GSUS and CombUS are associated with the development of erosions. GSUS appears to be an essential component of synovitis assessment and an independent predictor of joint damage progression in patients on biological DMARDs.

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