Head-to-head comparison of aggressive conventional therapy and three biological treatments and comparison of two de-escalation strategies in patients who respond to treatment: study protocol for a multicenter, randomized, open-label, blinded-assessor, phase 4 study Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial) Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial) Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Does the use of tumour necrosis factor antagonist therapy in poor prognosis, undifferentiated arthritis prevent progression to rheumatoid arthritis? Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial
Background New targeted therapies and improved treatment strategies have dramatically improved the outcomes of patients with rheumatoid arthritis ( RA ) . However , it is unknown whether different early aggressive interventions can induce stable remission or a low-active disease state that can be maintained with conventional synthetic disease-modifying antirheumatic drug ( csDMARD ) therapy , and whether they differ in efficacy and safety . The Nordic Rheumatic Diseases Strategy Trials And Registries ( NORD-STAR ) study will assess and compare ( 1 ) the proportion of patients who achieve remission in a head-to-head comparison between csDMARD plus glucocorticoid therapy and three different biological DMARD ( bDMARD ) therapies with different modes of action and ( 2 ) two de-escalation strategies in patients who respond to first-line therapy . Methods / design In a pragmatic , 80–160-week , multicenter , r and omized , open-label , assessor-blinded , phase 4 study , 800 patients with early RA ( symptom duration less than 24 months ) are r and omized 1:1:1:1 to one of four different treatment arms : ( 1 ) aggressive csDMARD therapy with methotrexate + sulphasalazine + hydroxychloroquine + i.a . glucocorticoids ( arm 1A ) or methotrexate + prednisolone p.o . ( arm 1B ) , ( 2 ) methotrexate + certolizumab-pegol , ( 3 ) methotrexate + abatacept , or ( 4 ) methotrexate + tocilizumab . The primary clinical endpoint is the proportion of patients reaching Clinical Disease Activity Index ( CDAI ) remission at week 24 . Patients in stable remission over 24 consecutive weeks enter part 2 of the study earliest after 48 weeks . Patients not achieving sustained CDAI remission over 24 consecutive weeks , exit the study after 80 weeks . In part 2 , patients are re-r and omized to two different de-escalation strategies , either immediate or delayed ( after 24 weeks ) tapering , followed by cessation of study medication . All patients remain on stable doses of methotrexate  . The primary clinical endpoint in part 2 is the proportion of patients in remission ( CDAI ≤2.8 ) 24 weeks after initiating treatment de-escalation . Radiographic assessment will be performed regularly throughout the trial , and blood and urine sample s will be stored in a biobank for later biomarker analyses . Discussion NORD-STAR is the first investigator-initiated , r and omized , early RA trial to compare ( 1 ) csDMARD and three different bDMARD therapies head to head and ( 2 ) two different de-escalation strategies . The trial has the potential to identify which treatment strategy to apply in early RA to achieve the best possible outcomes for both patients and society . Trial registration NCT01491815 and NCT02466581 . Registered on 8 December 2011 and May 2015 , respectively . EudraCT : 2011 - 004720 - Background : To investigate whether intensive treatment with methotrexate ( MTX ) according to a strict protocol and a computerised decision program is more beneficial compared to conventional treatment with MTX in early rheumatoid arthritis . Methods : In a two-year multicentre open label strategy trial , 299 patients with early rheumatoid arthritis were r and omly assigned to the intensive strategy group or the conventional strategy group . Patients in both groups received MTX , the aim of treatment being remission . Patients in the intensive treatment group came to the outpatient clinic once every month ; adjustment of the MTX dosage was tailored to the individual patient on the basis of predefined response criteria , using a computerised decision program . Patients of the conventional strategy group came to the outpatient clinic once every three months ; they were treated according to common practice . Cyclosporine was added if patients had an inadequate response to maximal tolerated MTX doses . Results : Seventy six ( 50 % ) patients in the intensive strategy group achieved at least one period of remission during the two year trial , versus 55 patients ( 37 % ) in the conventional strategy group ( p = 0.03 ) . Areas under the curve for nearly all clinical variables were significantly lower — that is , there was a better clinical effect for the intensive treatment group compared with the conventional treatment group . Conclusion : The results of this study show that it is possible to substantially enhance the clinical efficacy early in the course of the disease by intensifying treatment with MTX , aim ing for remission , tailored to the individual patient . Furthermore , participating rheumatologists indicated that the computerised decision program could be a helpful tool in their daily clinical practice Background Several agents provide treatment for established rheumatoid arthritis ( RA ) , but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis ( UA ) or very early RA . Objective To determine the impact of T-cell costimulation modulation in patients with UA or very early RA . Methods In this double-blind , phase II , placebocontrolled , 2-year study , anti-cyclic citrullinated peptide (CCP)2-positive patients with UA ( not fulfilling the ACR criteria for RA ) and clinical synovitis of two or more joints were r and omised to  abatacept  ( ∼10 mg/kg ) or placebo for 6 months ; the study drug was then terminated . The primary end point was development of RA ( by ACR criteria ) at year 1 . Patients were monitored by radiography , MRI , CCP2 , rheumatoid factor and 28 joint count Disease Activity Score ( DAS28 ) over 2 years . Results At year 1 , 12/26 ( 46 % ) abatacept-treated versus 16/24 ( 67 % ) placebo-treated patients developed RA ( difference ( 95 % CI ) −20.5 % ( −47.4 % to 7.8 % ) ) . Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients , respectively , were 0 versus 1.1 for total score , and 0 versus 0.9 for erosion score . Mean changes from baseline to year 1 in MRI erosion , osteitis and synovitis scores were 0 , 0.2 and 0.2 , respectively , versus 5.0 , 6.7 and 2.3 in the abatacept versus placebo groups . Safety was comparable between groups ; serious adverse events occurred in one patient ( 3.6 % ) in each group . Conclusion Abatacept delayed progression of UA/very early RA in some patients . An impact on radiographic and MRI inhibition was seen , which was maintained for 6 months after treatment stopped . This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease . Trial registration number NCT00124449 OBJECTIVE Several treatment strategies have proven value in the amelioration of rheumatoid arthritis ( RA ) , but the optimal strategy for preventing long-term joint damage and functional decline is unclear . We undertook this study to compare clinical and radiographic outcomes of 4 different treatment strategies , with intense monitoring in all patients . METHODS In a multicenter , r and omized clinical trial , 508 patients were allocated to 1 of 4 treatment strategies : sequential disease-modifying antirheumatic drug monotherapy ( group 1 ) , step-up combination therapy ( group 2 ) , initial combination therapy with tapered high-dose prednisone ( group 3 ) , and initial combination therapy with the tumor necrosis factor antagonist infliximab ( group 4 ) . Treatment adjustments were made every 3 months in an effort to obtain low disease activity ( a Disease Activity Score in 44 joints of < or = 2.4 ) . RESULTS Initial combination therapy including either prednisone ( group 3 ) or infliximab ( group 4 ) result ed in earlier functional improvement than did sequential monotherapy ( group 1 ) and step-up combination therapy ( group 2 ) , with mean scores at 3 months on the Dutch version of the Health Assessment Question naire ( D-HAQ ) of 1.0 in groups 1 and 2 and 0.6 in groups 3 and 4 ( P < 0.001 ) . After 1 year , mean D-HAQ scores were 0.7 in groups 1 and 2 and 0.5 in groups 3 and 4 ( P = 0.009 ) . The median increases in total Sharp/Van der Heijde radiographic joint score were 2.0 , 2.5 , 1.0 , and 0.5 in groups 1 - 4 , respectively ( P < 0.001 ) . There were no significant differences in the number of adverse events and withdrawals between the groups . CONCLUSION In patients with early RA , initial combination therapy including either prednisone or infliximab result ed in earlier functional improvement and less radiographic damage after 1 year than did sequential monotherapy or step-up combination therapy Objectives : To evaluate the ability of tumour necrosis factor ( TNF ) antagonist therapy to produce remission and prevent progression to rheumatoid arthritis ( RA ) in patients with poor prognosis undifferentiated inflammatory arthritis ( UA ) . Methods : Patients with UA of < 12 months ’ duration and having relapsed after a single parenteral corticosteroid injection were recruited into a double-blind , placebo-controlled trial of infliximab or placebo monotherapy administered at weeks 0 , 2 , 6 and 14 . Methotrexate was added at week 14 if no clinical response ( raised C-reactive protein ( CRP ) and clinical synovitis ) was achieved . St and ard outcomes were collected at baseline , infusion visits and weeks 26 and 52 . The primary outcome was clinical remission at week 26 . Results : 17 patients were r and omised ( 10 infliximab , 7 placebo ) all with poor prognostic features . At week 14 , the infliximab group had greater improvements in CRP and Health Assessment Question naire ( HAQ ) but by week 26 there was just a trend favouring infliximab for early morning stiffness , tender joint score , swollen joint score and HAQ ; there was no significant difference in 28 joint count Disease Activity Score between the two groups . Furthermore , only three patients were in clinical remission ( two infliximab , one placebo ) . By week 52 , 100 % patients in the infliximab group and 71 % ( 5/7 ) patients in the placebo group had developed RA . Conclusions : In poor prognosis UA , a short course of TNF antagonist therapy provided modest short-term relief but did not prevent the development of RA .  Patients with UA with a poor prognosis relapsing after corticosteroid have a high risk of evolving to RA and are suitable c and i date s for interventional treatment BACKGROUND Present treatment strategies for rheumatoid arthritis include use of disease-modifying antirheumatic drugs , but a minority of patients achieve a good response . We aim ed to test the hypothesis that an improved outcome can be achieved by employing a strategy of intensive outpatient management of patients with rheumatoid arthritis -- for sustained , tight control of disease activity -- compared with routine outpatient care . METHODS We design ed a single-blind , r and omised controlled trial in two teaching hospitals . We screened 183 patients for inclusion . 111 were r and omly allocated either intensive management or routine care . Primary outcome measures were mean fall in disease activity score and proportion of patients with a good response ( defined as a disease activity score < 2.4 and a fall in this score from baseline by > 1.2 ) . Analysis was by intention-to-treat . FINDINGS One patient withdrew after r and omisation and seven dropped out during the study . Mean fall in disease activity score was greater in the intensive group than in the routine group ( -3.5 vs -1.9 , difference 1.6 [ 95 % CI 1.1 - 2.1 ] , p<0.0001 ) . Compared with routine care , patients treated intensively were more likely to have a good response ( definition , 45/55 [ 82 % ] vs 24/55 [ 44 % ] , odds ratio 5.8 [ 95 % CI 2.4 - 13.9 ] , p<0.0001 ) or be in remission ( disease activity score < 1.6 ; 36/55 [ 65 % ] vs 9/55 [ 16 % ] , 9.7 [ 3.9 - 23.9 ] , p<0.0001 ) . Three patients assigned routine care and one allocated intensive management died during the study ; none was judged attributable to treatment . INTERPRETATION A strategy of intensive outpatient management of rheumatoid arthritis substantially improves disease activity , radiographic disease progression , physical function , and quality of life at no additional cost
OBJECTIVE To identify tools design ed to evaluate the severity of patients with rheumatoid arthritis ( RA ) in order to use them in the investigation of prognostic markers in early arthritis .