Sustained Drug-free Remission Research Articles

Outcomes and Predictors of Sustained Remission After Drug Withdrawal in Pediatric Crohn Disease.

The primary aim of this study was to determine the proportion of pediatric Crohn disease (CD) subjects in sustained drug-free remission 52 weeks after stopping pharmacological therapy. We also aimed to explore the effects of the Crohn Disease Exclusion Diet (CDED) and microbiome composition on remission. We performed a prospective study following 18 CD patients ages 13-21 years in deep clinical remission withdrawing from immunomodulator (n = 7) or anti-TNFα (n = 11) monotherapy at two tertiary care centers. Stool for calprotectin and microbiome analyses was collected over 52 weeks. Participants followed either the CDED or free diet after drug withdrawal. The primary endpoint was sustained relapse-free drug-free remission (calprotectin <250 µg/g) at 52 weeks. Seventeen participants were followed through 52 weeks with 11 (64.7%) in sustained remission. There was no improvement in remission among participants following the CDED (5/9; 55.6%), P = 0.63. By 104 weeks, only 8 (47.1 %) participants remained off immunosuppressive therapies. Analysis of shotgun metagenomic sequence data revealed that taxonomic and gene function abundance in the gut microbiome was relatively stable for participants in remission and relapse. However, a predictive model incorporating gut microbial gene pathway abundance for amino sugar/nucleotide sugar metabolism and galactose metabolism from baseline samples predicted relapse at 52 weeks with 80% accuracy. After withdrawal of immunomodulator or anti-TNFα monotherapy among a small cohort of pediatric CD subjects in deep remission, nearly 65% sustained remission at 52 weeks. Baseline microbiome alterations predicted relapse. Large prospective studies are needed to better understand outcomes after treatment de-escalation.

Towards preventive treatment of rheumatoid arthritis

Prevention of rheumatoid arthritis is an ambitious therapeutic goal. Once it has developed, rheumatoid arthritis is characterised by high chronicity and often requires lifelong treatment.1,2 Sustained drug-free remission is rare, especially in seropositive disease, which is defined by the presence of rheumatoid factor and anti-citrullinated protein antibodies (ACPA).3 Onset of rheumatoid arthritis, characterised by joint swelling, is preceded by a pre-arthritis phase, in which patients show discrete symptoms (eg, pain), presence of autoantibodies (rheumatoid factor and ACPA), and subclinical signs of inflammation (eg, tenosynovitis) on an ultrasound or MRI scan.

OP0279 CAR-T CELL TREATMENT OF REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS- SAFETY AND PRELIMINARY EFFICACY DATA FROM THE FIRST FOUR PATIENTS

BackgroundWhile treatment of Systemic lupus erythematosus (SLE) has substantially improved, a subset of patients experiences severe progressive disease despite T- and B cell targeted therapy. Furthermore, drug-free remission and seroconversion is difficult to achieve in SLE to dateObjectivesTo study the safety, tolerability, and preliminary efficacy of deep B cell depletion using autologous CD19 chimeric antigen receptor (CAR) T cells in patients with severe and treatment-refractory SLEMethodsThe CAR product was manufactured by CliniMACS Prodigy system (Miltenyi Biotec, Bergisch Gladbach, Germany). T-cells were enriched from the patients’ peripheral blood apheresis product and 1x108 cells were used as starting cell population. The cells were transfected with a lentiviral vector encoding an anti-CD19 CAR is composed of the FMC63 scFv, a CD8- derived hinge region, TNFRSF19-derived transmembrane domain, CD3ζ intracellular domain, and 4-1BB co-stimulatory domain (Miltenyi Biotec) and expanded for 12 days. After conditioning with cyclophosphamide/ fludarabine patients received 1x106 CD19-CAR-T cells/kg body weight as a single infusion. All SLE treatments with the exception of low dose prednisolone were stopped before CAR-T cell administration. After CAR-T cell treatment, also prednisolone was stopped. Tolerability was assessed by monitoring for Cytokine-release syndrome (CRS), immune-related effector cell neurotoxicity syndrome (ICANS) and infections. Preliminary efficacy was assessed by reaching a Lupus Low Disease Activity State (LLDAS), seroconversion in dsDNA antibodies and ANA and cessation of all SLE-specific treatmentsResultsAs of January 22, 2022, our 4 SLE patients had been treated with CD19 CAR-T cells with a follow up of 10 months (patient 1, female aged 20, SLEDAI-2K: 16), 7 months (patient 2, male aged 22; SLEDAI-2K:8), 2 months (patient 3, female aged 22; SLEDAI 2K: 6), and 1 month (patient 4; female aged 24; SLEDAI-2K: 6), respectively. All patients had active severe SLE with failure of standard treatment including pulsed steroids, hydroxychloroquine, mycophenolate, cyclophosphamide, intravenous immunoglobulins, rituximab and belimumab before CD19 CAR-T cell administration. All patients had active kidney disease. No infections occurred. All four patients experienced fever without proof of infectious disease (CRS °I); only one patient was treated with a single dose of tocilizumab. No ICANS and no CRS of other organs occurred. In vivo, CAR-T cells rapidly expanded to a maximum of 27,6% (day 9, patient 1), 41,2% (day 9, patient 2), 11,5% (day 9, patient 3) and 59,1% (day 9, patient 4) of total circulating T cells followed by a typical decline, with circulating CAR-T cells being continuously detectable during the next months. Expansion of CAR T cells preceded the complete and sustained depletion of circulating B cells. Patient 1 experienced sustained drug-free remission (SLEDAI-2K=0) with complete loss of ANA and dsDNA antibodies despite reappearance of B cells at 6 months. Patient 2 also experienced complete loss of ANA and dsDNA antibodies with B cells not yet returned. Low-level proteinuria remained most likely due to previously accrued damage in glomerular filter function (SLEDAI-2K: 2). Patient 3 and patient 4 had a shorter observation period to date but also achieved clinical remission (both SLEDAI-2K 0). All patients met LLDAS and could successfully stop all SLE-specific medication, including glucocorticoids. No SLE flare occurred so far.ConclusionTaken together, these data show that CD19 CAR T-cell therapy is well tolerated and may induce rapid remission of severe refractory SLE.

Treatment Outcomes in Birdshot Chorioretinitis: Corticosteroid Sparing, Corticosteroid Discontinuation, Remission, and Relapse

To describe treatment-related outcomes among patients with birdshot chorioretinitis (BSCR). Retrospective cohort study. Patients diagnosed with BSCR at 2 tertiary care academic medical centers. Clinical and treatment-related data were collected for all patients with BSCR diagnosed between 2003 and 2017 at the 2 centers and for each eye at each clinical visit. Four outcomes were considered: (1) corticosteroid-sparing success, defined as inactive disease and prednisone dose of ≤7.5 mg/day; (2) corticosteroid-discontinuation success, defined as inactive disease and discontinuation of prednisone; (3) sustained drug-free remission, defined as inactive disease off all medications for ≥3 months; and (4) relapse of BSCR after remission. A total of 107 patients with BSCR were identified, of whom 94 had follow-up data. Corticosteroid-sparing success was achieved in 95.4% of the oral corticosteroid-treated patients at a rate of 0.60 successes per person-year (PY) (95% CI: 0.50/PY, 0.70/PY). The median time to corticosteroid-sparing success was 12 months. Corticosteroids were discontinued successfully in 76.5% of oral corticosteroid-treated patients (rate= 0.28/PY; 95% CI: 0.21/PY, 0.35/PY). The median time to successful corticosteroid discontinuation was 2.0 years. A sustained drug-free remission was achieved in 24 patients (rate= 0.06/PY; 95% CI: 0.04/PY, 0.09/PY), with approximately 25% of patients achieving remission by 4 years of follow-up. Relapse of inflammation in patients after achieving a sustained, drug-free remission occurred at a rate of 0.24/PY (95% CI: 0.14/PY, 0.37/PY). Successful corticosteroid sparing and discontinuation was achieved in the majority of patients with BSCR. Remission occurred less often, but data were limited by the time needed to induce a remission (4 years) and the amount of follow-up (median, 4.6 years). The relapse rate after a remission was 0.24/PY.

Biomarkers of tolerance in immune-mediated inflammatory diseases: a new era in clinical management?

Modern therapeutic agents and treatment regimens have made sustained remission an attainable target for many patients across a spectrum of immune-mediated inflammatory diseases, albeit at the risk of adverse events and the expense of drug prescription and safety monitoring. Clinicians and patients are thus increasingly faced with a novel treatment dilemma: whether and how best to stop immunomodulatory treatment in patients who achieve remission. In this final paper in a Series on therapeutic tolerance induction, we summarise our current knowledge of biomarkers of immune homeostasis in immune-mediated inflammatory diseases and their application to the prediction and attainment of sustained drug-free remission. We summarise evidence from prospective studies of immunomodulatory drug cessation across a range of immune-mediated inflammatory diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, and inflammatory bowel disease. We also consider current evidence for clinical, serological, proteomic, metabolomic, cellular, and microbiomic biomarkers of immune homeostasis. Finally, we discuss the steps necessary for clinical translation of these biomarkers, as well as the potential transformative effect of these biomarkers on management of patients with immune-mediated inflammatory diseases if clinical translation is successfully achieved.

Update on the treatment of nonsystemic juvenile idiopathic arthritis including treatment-to-target: is (drug-free) inactive disease already possible?

This review concerns the outcome for nonsystemic juvenile idiopathic arthritis (JIA) with emphasis on treatment-to-target (T2T) and treatment strategies aiming at inactive disease by giving an overview of recent articles. More efficacious therapies and treatment strategies/T2T with inactive disease as target, have improved the outcome for JIA significantly. Recent studies regarding treatment strategies have shown 47-68% inactive disease after 1 year. Moreover, probability of attaining inactive disease at least once in the first year seems even higher in recent cohort-studies, reaching 80%, although these studies included relatively high numbers of oligoarticular JIA patients. However, 26-76% of patients flare upon therapy withdrawal and prediction of flares is still difficult. Remission can be achieved and sustained in (some) JIA patients, regardless of initial treatment. Cornerstone principles in the management of nonsystemic JIA treatment are early start of DMARD therapy, striving for inactive disease and T2T by close and repeated monitoring of disease activity. T2T and tight control appear to be more important than a specific drug in JIA. Next to inactive disease, it is important that patients/parents are involved in personal targets, like reduction of pain and fatigue. Future studies should focus on predictors (based on imaging-methods or biomarkers) for sustained drug-free remission and flare.

Earlier is better when treating rheumatoid arthritis: but can we detect a window of opportunity?

ObjectivesThe window of opportunity (WOO) hypothesis suggests a limited time frame to stop rheumatoid arthritis (RA). We hypothesised that a WOO could either be represented by a hyperbolic (‘curved’) decline in the chance to achieve the outcome sustained drug-free remission (sDFR) over time, after which achieving sDFR is not possible anymore, or by a more gradual linear decline approaching zero chance to achieve sDFR.MethodsPatients with RA (symptom duration <2 years) were included from two randomised trials: BehandelStrategieën (BeSt), n=508 and Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease (IMPROVED), n=479. Cox-regression was performed to assess the shape of the association between symptom duration and sDFR (Disease Activity Score<1.6, no disease-modifying anti-rheumatic drugs for ≥1 year) for patients starting slow-acting monotherapy (IMPROVED, BeSt) or fast-acting combination therapy (BeSt). Likelihood ratio tests were used to compare the fit of linear and non-linear models in both databases separately. Predictions from the best fitting models were used to assess whether the absolute risk to achieve sDFR approaches zero with increasing symptom duration.ResultsIn BeSt and IMPROVED, 54/226 and 110/421 patients achieved sDFR with fast-acting treatment, and 53/243 (BeSt) with slow-acting treatment. Non-linear models did not fit better than linear models (fast-acting treatment BeSt p=0.743, IMPROVED p=0.337; slow-acting treatment BeSt p=0.609). After slow-acting monotherapy, linear models declined steeper. None of the models approached zero chance to achieve sDFR over time.ConclusionsThe chance to achieve sDFR decreased gradually over time, and decreased fastest in patients starting slow-acting monotherapy. In both treatment groups, we found no evidence for a WOO within 2 years symptom duration.

Sustained Drug Free Remission of Lupus Panniculitis with Methotrexate: A Report From Nepal

Cutaneous manifestations are second most common presenting feature of lupus. Discoid lupus erythematosus is the most common variant amongst all; lupus panniculitis being described in only 2-5% of cases. Most cases of cutaneous lupus are associated with autoantibodies and either precede or follow the systemic manifestations of lupus. There is no proven treatment for cutaneous manifestations of lupus including lupus panniculitis. Available non-randomized studies show efficacy of hydroxychoroquine in most cases, whereas methotrexate and other immunosuppressant are used in relapsing cases. We describe a case of lupus panniculitis presenting as isolated manifestation of lupus with negative autoantibody titers which responded well to methotrexate. We observed that lesions went into drug free remission in 1 year and did not recur on 1 year follow-up. There was no residual skin atrophy or scarring. Drug free remission in isolated cases of lupus panniculitis variant could be possible with timely intervention in the absence of autoantibodies. Keywords: lupus; Methotrexate; Nepal; panniculitis.

High Rate of Drug-Free Remission After Induction Therapy With Golimumab in Early Peripheral Spondyloarthritis.

New treatment algorithms using tumor necrosis factor (TNF) blockers in early stages of spondyloarthritis (SpA) induce high rates of clinical remission or low disease activity. It could be anticipated that such early intervention strategies in peripheral SpA may induce drug-free remission. We undertook this study to evaluate drug-free clinical remission after induction therapy with golimumab inpatients with very early active peripheral SpA, and to identify patient characteristics that predict sustained drug-free remission. Eligible patients were age ≥18 years and fulfilled the Assessment of SpondyloArthritis international Society criteria for peripheral SpA. All patients had symptom durationof <12 weeks. Sustained clinical remission wasdefined as the absence of arthritis, enthesitis, and dactylitis at 2 consecutive major visits, after which treatment was withdrawn. Patients were prospectively followed up to assess the rate of sustained drug-free clinical remission and clinical relapse. Eighty-two percent of patients (49 of 60) fulfilled sustained clinical remission criteria after a regimen of induction therapy with golimumab. The majority of patients already reached this status at week 24 (n = 30), with an additional 11 and 8 patients at weeks 36 and 48, respectively. All patients had a follow-up period of at least 18 months after drug withdrawal. Fifty-three percent of patients (26 of 49) still have drug-free remission of their disease.Inability to sustain drug-free remission was associated with the presence of psoriasis and polyarticular disease (swollen joint count >5). Anti-TNF treatment in very early peripheral SpA results in a remarkably high rate of sustained clinical remission. More than 50% of patients continue to have remission of their disease after withdrawal of therapy, which highlights a defined window of opportunity permitting induction of drug-free remission.

Baseline metabolic profiles of early rheumatoid arthritis patients achieving sustained drug-free remission after initiating treat-to-target tocilizumab, methotrexate, or the combination: insights from systems biology

BackgroundWe previously identified, in newly diagnosed rheumatoid arthritis (RA) patients, networks of co-expressed genes and proteomic biomarkers associated with achieving sustained drug-free remission (sDFR) after treatment with tocilizumab- or methotrexate-based strategies. The aim of this study was to identify, within the same patients, metabolic pathways important for achieving sDFR and to subsequently study the complex interactions between different components of the biological system and how these interactions might affect the therapeutic response in early RA.MethodsSerum samples were analyzed of 60 patients who participated in the U-Act-Early trial (ClinicalTrials.gov number NCT01034137) and initiated treatment with methotrexate, tocilizumab, or the combination and who were thereafter able to achieve sDFR (n = 37); as controls, patients were selected who never achieved a drug-free status (n = 23). Metabolomic measurements were performed using mass spectrometry on oxidative stress, amine, and oxylipin platforms covering various compounds. Partial least square discriminant analyses (PLSDA) were performed to identify, per strategy arm, relevant metabolites of which the biological pathways were studied. In addition, integrative analyses were performed correlating the previously identified transcripts and proteins with the relevant metabolites.ResultsIn the tocilizumab plus methotrexate, tocilizumab, and methotrexate strategy, respectively, 19, 13, and 12 relevant metabolites were found, which were subsequently used for pathway analyses. The most significant pathway in the tocilizumab plus methotrexate strategy was “histidine metabolism” (p < 0.001); in the tocilizumab strategy it was “arachidonic acid metabolism” (p = 0.018); and in the methotrexate strategy it was “arginine and proline metabolism” (p = 0.022). These pathways have treatment-specific drug interactions with metabolites affecting either the signaling of interleukin-6, which is inhibited by tocilizumab, or affecting protein synthesis from amino acids, which is inhibited by methotrexate.ConclusionIn early RA patients treated-to-target with a tocilizumab- or methotrexate-based strategy, several metabolites were found to be associated with achieving sDFR. In line with our previous observations, by analyzing relevant transcripts and proteins within the same patients, the metabolic profiles were found to be different between the strategy arms. Our metabolic analysis further supports the hypothesis that achieving sDFR is not only dependent on predisposing biomarkers, but also on the specific treatment that has been initiated.Trial registrationClinicalTrials.gov, NCT01034137. Registered on January 2010

Reversing Autoimmunity Combination of Rituximab and Intravenous Immunoglobulin.

In this concept paper, the authors present a unique and novel protocol to treat autoimmune diseases that may have the potential to reverse autoimmunity. It uses a combination of B cell depletion therapy (BDT), specifically rituximab (RTX) and intravenous immunoglobulin (IVIg), based on a specifically designed protocol (Ahmed Protocol). Twelve infusions of RTX are given in 6–14 months. Once the CD20+ B cells are depleted from the peripheral blood, IVIg is given monthly until B cells repopulation occurs. Six additional cycles are given to end the protocol. During the stages of B cell depletion, repopulation and after clinical recovery, IVIg is continued. Along with clinical recovery, significant reduction and eventual disappearance of pathogenic autoantibody occurs. Administration of IVIg in the post-clinical period is a crucial part of this protocol. This combination reduces and may eventually significantly eliminates inflammation in the microenvironment and facilitates restoring immune balance. Consequently, the process of autoimmunity and the phenomenon that lead to autoimmune disease are arrested, and a sustained and prolonged disease and drug-free remission is achieved. Data from seven published studies, in which this combination protocol was used, are presented. It is known that BDT does not affect check points. IVIg has functions that mimic checkpoints. Hence, when inflammation is reduced and the microenvironment is favorable, IVIg may restore tolerance. The authors provide relevant information, molecular mechanism of action of BDT, IVIg, autoimmunity, and autoimmune diseases. The focus of the manuscript is providing an explanation, using the current literature, to demonstrate possible pathways, used by the combination of BDT and IVIg in providing sustained, long-term, drug-free remissions of autoimmune diseases, and thus reversing autoimmunity, albeit for the duration of the observation.

Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation, which affects approximately 1% of the population. The benefit of early recognition and treatment has led to an increased interest in the early phases of disease. With the aim of classifying patients earlier in their disease course, new RA classification criteria have been developed. Much attention has been devoted to the identification in the prearthritis phase of arthralgia. The discovery of new risk factors and autoantibodies has led to new theories about the putative mechanisms involved in disease development. Finally, the outcome measures have also evolved, with more emphasis on sustained drug-free remission and patient-reported outcomes. This article reviews the new developments in RA research and discusses the latest insights into epidemiology, risk factors, predisease states, and outcomes.

Long-term disease and patient-reported outcomes of a continuous treat-to-target approach in patients with early rheumatoid arthritis in daily clinical practice

Patients in real life may differ from those in clinical trials. The aim of this study is to report 5-year outcomes of a continuous treat-to-target (T2T) approach in patients with rheumatoid arthritis (RA) in daily clinical practice. In the Dutch RhEumatoid Arthritis Monitoring cohort, all patients with a clinical diagnosis of RA were treated according to a protocolled T2T strategy, aimed at 28-joint Disease Activity Score (DAS28) < 2.6. Outcomes were percentages of patients in distinct levels of disease activity, mean course of DAS28 and prevalence of sustained (drug-free) remission. Also, data on functional disability (Health Assessment Questionnaire) and health-related quality of life (Short-Form 36) were examined. Mean DAS28 improved from 4.93 (95% CI 4.81–5.05) at baseline to 2.49 (95% CI 2.35–2.63) after 12 months and remained stable thereafter. Percentages of patients at 12 months with DAS28 < 2.6 (remission), DAS28 ≥ 2.6 and ≤ 3.2 (low disease activity), DAS28 > 3.2 and ≤ 5.1 (moderate disease activity) and DAS28 > 5.1 (high disease activity) were 63, 16, 18 and 3%, respectively. Sustained remission (DAS28 < 2.6 during ≥ 6 months) was observed at least once in 84% of the patients and drug-free remission (DAS28 < 2.6 during ≥ 6 months after withdrawal of all disease-modifying anti-rheumatic drugs) in 36% of the patients. Functional disability and health-related quality of life significantly improved during the first 24 weeks. Continuous application of T2T in real-life RA patients leads to favourable disease- and patient-related outcomes.

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

To 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. In 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. After 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. Five 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.

Identification of differential co-expressed gene networks in early rheumatoid arthritis achieving sustained drug-free remission after treatment with a tocilizumab-based or methotrexate-based strategy

BackgroundMethotrexate is endorsed to be used as first-line treatment in rheumatoid arthritis (RA). However, a large proportion of patients need additional treatment with a biological disease-modifying anti-rheumatic drug (DMARD) to adequately suppress their disease activity. A better understanding of genotypes could help to distinguish between patients with different pathogenic mechanisms. The aim of this study was therefore to identify networks of genes within DMARD-naive early RA patients associated with achieving sustained drug-free remission (sDFR) after initiating tocilizumab plus methotrexate, tocilizumab, or methotrexate therapy.MethodsSamples were used from 60 patients from the U-Act-Early study who received tocilizumab plus methotrexate, tocilizumab, or methotrexate therapy, and who achieved sDFR (≥3 months in drug-free remission until the end of the study, n = 37) after therapy was tapered and subsequently stopped, or who were not able to discontinue the therapy as controls (n = 23). Whole blood samples were collected and ribonucleic acid (RNA) was isolated from positive cluster of differentiation 4 (CD4+) and CD14+ cells and analysed using high-throughput sequencing. Weighted gene co-expression network analyses were performed to identify clusters (i.e. modules) of differently expressed genes associated with achieving sDFR and which were subsequently used for pathway analyses.ResultsNetwork analyses within CD4+ cells identified two significant modules in the tocilizumab plus methotrexate arm and four modules in the tocilizumab and methotrexate arms, respectively (p ≤ 0.039). Important pathways in the module best correlating with achieving sDFR were in the tocilizumab plus methotrexate arm related to processes involved with transcription and translation; in the tocilizumab arm, pathways were related to migration of white blood cells and G-protein coupled receptors, and in the methotrexate arm pathways were involved with the response to a bacterial or biotic (i.e. biological material)-related stimulus. No relevant networks could be identified in the sequenced CD14+ cells.ConclusionsWithin networks of co-expressed genes, several pathways were found related to achieving sDFR after initiating therapy with tocilizumab, methotrexate, or the combination. Between the three strategy arms, we identified different networks of predisposing genes which indicates that specific gene expression profiles, depending on the treatment strategy chosen, are associated with a higher chance of achieving sDFR.Trial registrationClinicaltrials.gov, NCT01034137. Registered on 16 December 2009.

Predictors of sustained drug-free diabetes remission over 48 weeks following short-term intensive insulin therapy in early type 2 diabetes

ObjectiveIn early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) for 2–4 weeks can decrease insulin resistance, reduce glucagonemia, improve β-cell function, and even induce a remission of diabetes...

Sustained biologic-free and drug-free remission in rheumatoid arthritis, where are we now?

The advent of new medications and new treatment strategies for rheumatoid arthritis has made it possible to achieve remission in more patients than before. Furthermore, recent clinical trials and register studies suggest that some patients who initially required aggressive therapy may achieve biologic-free remission or even the ultimate goal of therapy, drug-free remission, resembling recovery. Here, we present a discursive review of the most important studies addressing these issues. Based on the overall results, it remains unclear if achieving biologic-free and drug-free remissions are primarily due to the natural course of the disease or to the early therapeutic intervention according to the ‘window of opportunity’ hypothesis. Although medication-free remission is only achievable in a small subset of patients, characterizing this patient cohort may provide important information about beneficial prognostic factors and the underlying mechanisms. In summary, in a subset of patients biologic-free and even drug-free remission can be achieved; pursuing these possibilities in practice may decrease the risk for long-term side effects and attenuate the economic burden of the disease.

Patients with early arthritis consume less alcohol than controls, regardless of the type of arthritis

There are conflicting reports concerning the association between alcohol consumption and RA. We performed a case-control study to investigate the association of alcohol consumption with RA as well as with other forms of arthritis. To assess whether alcohol consumption affects long-term disease outcome, we also investigated its association with radiographic progression and sustained drug-free remission in RA. Patients with arthritis and various diagnoses including RA, OA, ReA, SpA and PsA were compared with 5868 controls from the general population. The association of disease with alcohol consumption was analysed by logistic regression analysis. Alcohol consumption was inversely associated with not only RA [odds ratio (OR) 0.28, 95% CI 0.23, 0.35] but also OA (OR 0.31, 95% CI 0.16, 0.62) and other forms of arthritis (OR 0.34, 95% CI 0.24, 0.48). A higher degree of systemic inflammation, reflected by the ESR and CRP level, was associated with a smaller proportion of patients consuming alcohol. There was no dose-response relationship between the amount of alcohol consumed and the presence of arthritis. The extent of joint destruction and the rate of sustained drug-free remission were not affected by alcohol consumption. Arthritis patients report less alcohol consumption than controls, regardless of the type of arthritis. This suggests that alcohol may either protect against different kinds of arthritis or that the inverse association between alcohol and arthritis may be secondary to disease development, with arthritis patients being less inclined to consume alcohol due to their decreased general well-being.

OP0154 Clinical and radiological outcomes of four disease activity driven treatment strategies: 8-year results of the best study

ObjectivesTo compare clinical and radiological outcomes of 8 years targeted treatment with four treatment strategies in recent onset rheumatoid arthritis (RA) patients.MethodsPatients (n=508) with recent onset RA were randomized to...

Sustained drug-free remission in rheumatoid arthritis after DAS-driven or non-DAS-driven therapy: a comparison of two cohort studies

To compare the prevalence of and predictors for sustained drug-free remission in two cohorts of patients with recent-onset RA treated with DAS-driven therapy or non-DAS-driven therapy. Sustained drug-free remission was assessed after 5 years of follow-up in 508 patients treated with DAS-driven therapy (DAS ≤ 2.4) in a randomized treatment cohort, and in 424 patients who received non-DAS-driven therapy in a prospective inception cohort. The design of the DAS-driven cohort required systematic joint assessments with DAS-driven restart of therapy. Predictors for remission were identified by univariable and multivariable logistic regression in each cohort separately and in a combined multivariate logistic regression analysis corrected for propensity scores, including a sensitivity analysis on patients receiving initial monotherapy. Patients in the DAS-driven cohort had more active disease at baseline, but the prevalence of sustained drug-free remission was similar after DAS-driven (9.8%) and non-DAS-driven therapy (10.6%). Among patients with ACPA, drug-free remission was more frequently achieved after DAS-driven than after non-DAS-driven therapy (5.4 vs. 2.1%, OR = 2.68, 95% CI 0.97, 7.43). Absence of ACPA and short symptom duration were independent predictors for sustained drug-free remission in both cohorts. Initial treatment choice and inclusion period were not predictive. The sensitivity analysis yielded comparable results. Retrospectively comparing a DAS-driven to a non-DAS-driven therapy cohort, the occurrence and predictors of sustained drug-free remission were similar. The DAS-driven cohort had a more unfavourable prognosis. DAS-driven therapy may improve the chance of sustained drug-free remission in ACPA-positive patients with recent-onset RA.