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Introduction: Atopic dermatitis (AD) is a chronic, relapsing–remitting illness. In moderate-to-severe instances, recommendations urge patient-centered systemic therapy. Existing standards lack long-term treatment success requirements. A treat-to-target methodology was proposed for systemic therapy patients that requires global improvements to prompt decisions about treatment. Methods: We conducted an observational study between May 2021 and June 2022 in three Ecuadorian patients with severe AD who were treated with dupilumab to assess the clinical evolution and behavior of the subdomains evaluated by clinimetric tools. Results: Patients A and C satisfied disease-domain response criteria to dupilumab at 12 and 24 weeks, but B did not complete the algorithm objectives. Nonetheless, patient A improved AD severity, itching, bleeding, desquamation, sleep, daily activities, mood, emotions, sexual troubles, clothing, and sports subdomains. Patient B experienced reduced symptomatology, AD aggravation, daily activities impact, and work/study impairment. Patient C improved from severe to mild desquamation, itching, exudate, lichenification, and rough/dry skin. Sleep, shame, and study subdomains improved the most. Conclusion: We provide a new operational construct for analyzing current patient-reported outcome measures (PROMs) and clinician-reported outcome measures (CROMs) based on subdomains to widen our understanding of the state of disease activity and make clinical decisions when the treat-to-target strategy is not attained.

Introduction: Drug-free remission (DFR) and its maintenance have been defined as the most desirable outcome for rheumatoid arthritis (RA) patients. DFR is linked to resolution of arthritis-related symptoms and restoration of normal functioning. However, there is currently no consensus if an optimal strategy, upon the initiation of treatment to the proper drugs withdrawal, is enough to induce it, or whether it is a predetermined condition related to patients' intrinsic characteristics. Areas covered: This review focuses on two key concepts around DFR. First, we analyze patients' intrinsic factors that may increase the chance of DFR, regardless of therapeutic choices. Second, we discuss on the evidence that it can be induced thanks to adequate, extrinsic disease management. Finally, we provide a glimpse into consequences of drugs discontinuation .Expert opinion: The early initiation of DMARD and the subsequent strict monitoring and drug adjustments are of primary importance to allow patients to achieve DFR, irrespective of initial treatment strategy. Once remission is obtained and maintained, it is possible to gradually taper and discontinue drugs with no dramatic consequences on the disease course. Among those who stop medication, ACPA-negative patients more often maintain the remission. Thus, DFR might depend on a combination of intrinsic and extrinsic factors.

Systemic lupus erythematosus (SLE) is the most representative disorder within systemic autoimmune diseases. The treat-to-target strategy in SLE was established half a decade ago and, since then, remarkable advances have been made. An international consensus has defined and unified the term remission and also low disease activity has been proposed as an alternative and, perhaps, more realistic target. Both of them have proven to be meaningful in terms of improving several outcomes, and have opened the path for future research in clinical trials. RESUMEN El lupus eritematoso sistémico (LES) es el trastorno más representativo dentro de las enfermedades autoinmunes sistémicas. La estrategia de tratamiento por objetivos en el LES se estableció hace media década y desde entonces se han producido notables avances. Un consenso internacional ha definido y unificado el término remisión y también se ha propuesto la baja actividad de la enfermedad como un objetivo alternativo y quizás más realista. Ambos han demostrado ser significativos en cuanto a la mejora de varios resultados y han abierto el camino para futuras investigaciones en ensayos clínicos.

Objective: To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials. Methods: The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria. Results: The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0–3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics. Conclusions: A cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.

Objectives The STRATEGE (Therapeutic Strategy in Patients Treated With Methotrexate for Rheumatoid Arthritis) study aimed to describe treatment strategies in current practice in RA biologic DMARD (bDMARD)-naïve patients with an inadequate response to MTX therapy, and to compare clinical efficacy of the different therapeutic strategies on disease activity after 6 months. Methods The main inclusion criteria of this prospective, observational, multicentre study were confirmed RA diagnosis, treatment by MTX monotherapy and need for therapeutic management modification. Results The 722 patients included had a mean (s.d.) RA duration of 5.3 (6.7) years, a mean DAS28 of 4.0 (1.1); they were all receiving MTX monotherapy, 68% oral, at a mean dose of 15.0 (4.1) mg/week. Two major strategies were identified: (i) MTX monotherapy dose and/or route optimization (72%) and (ii) bDMARD initiation ± MTX (16%). MTX dosing was modified for 70% of patients, maintained (dose and route) for 28% of patients and interrupted for 2%. bDMARDs were started when the MTX mean dose was 17.4 mg/week, 56% parenterally; MTX was maintained concomitantly for 96% of patients. Six-month follow-up results adjusted by propensity score showed that both options were equally successful in improving disease activity and physical function, with 63 and 68% of good-to-moderate EULAR responses, respectively. Conclusion The STRATEGE study shows the importance of initial MTX treatment optimization before initiation of a biological treatment and emphasizes the importance of treat-to-target strategy. Trial registration ClinicalTrials.gov NCT02288520.

The treat-to-target strategy has been recently suggested in the management of Systemic Lupus Erythematosus (SLE). Lupus Low Disease Activity State (LLDAS) and Definitions Of Remission In SLE (DORIS) remission were outlined as two concentric targets. The achievement of LLDAS was shown to be associated with lower frequency of SLE flare, decreased damage progression, better quality of life, and reduced mortality. In addition, LLDAS has successfully been tested in post-hoc analyses of a number of randomized controlled trials. However, it has been recently underlined that LLDAS includes a high proportion of patients in remission, raising the question if these endpoints are sufficiently distinct to consider their separation clinically relevant. Some studies suggest that the protective effect of LLDAS on damage might be due to the inclusion of patients who are in remission. Notably, clinical low disease activity (LDA) seems to be uncommon in SLE due to the relapsing-remitting pattern of the disease, in which low level of activity only occurs transiently. Moreover, since the domains included in LLDAS have several limitations, such as the use of a binomial disease activity index, the exclusion of some mild manifestations and the consideration of items subjected to variability (physician global assessment and glucocorticoids dose), not all patients in LDA are adequately represented by LLDAS.

Introduction: Treat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project ‘Treat to Target Italia’ was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations. Methods: On the basis of the published literature, their clinical experience, and the results of a survey among Italian dermatologists, the SB identified four relevant topics: (1) clinical remission; (2) quality of life; (3) abrogation of systemic inflammation; (4) safety. They drafted 20 statements addressing these four topics and submitted them to a panel of 28 dermatologists, in a Delphi process, to achieve consensus (greater than 80% agreement). Results: Consensus was reached on all statements. Treatment goals defining clinical remission should include a 90% improvement from baseline in the Psoriasis Area and Severity Index (PASI90 response) or an absolute PASI score of less than or equal to 3. Patient’s quality of life and satisfaction are important targets. If PASI targets are achieved, there should be no or very low impact of psoriasis on quality of life [Dermatology Life Quality Index (DLQI) score less than or equal to 3]. If PASI or DLQI goals are not achieved within 3–4months, treatment should be changed. Abrogation of systemic inflammation may be crucial for preventing or delaying inflammatory comorbidities. Safety is an equally important target as efficacy. Conclusion: These 20 consensus statements define the parameters of a treat-to-target strategy for psoriasis in Italy. It is hoped that use of these in the management of patients with psoriasis will improve treatment outcomes and patient health-related quality of life.

A treat-to-target strategy, in which treatment is continuously adjusted according to the results of scheduled objective monitor ing, is optimal for patients with Crohn’s disease (CD) in the era of biologics. The small bowel is a common site of intractable CD, which may result from multiple strictures or expanding lesions. To improve the prognosis of patients with small bowel CD, le sions should be proactively monitored within the subclinical phase. Objective assessment of small bowel lesions is technically difficult, however, due to the relatively poor correlation between endoscopic activity and clinical symptoms or biomarker titers. The presence of proximal small bowel lesions and asymptomatic “Real Silent CD” must be considered. Endoscopy remains the gold standard to assess these lesions. In clinical practice, the advantages and disadvantages of each imaging modality and bio marker must be carefully weighed for appropriate application and reliable monitoring. The prevalence of small bowel lesions depends on the precision of the imaging modality used for detection. Clinical management should be based on the dominant location of the intestinal lesions rather than classical classification. Optimal strategies for detecting and treating small bowel le sions in patients with CD must be developed utilizing reliable, precise, and objective monitoring. (Intest Res 2020;18:347-354)

Objectives An efficient pharmacological response to MTX treatment in RA patients relies on the retention and accumulation of intracellular MTX-polyglutamates catalysed by the enzyme folylpolyglutamate synthetase (FPGS). We recently identified a partial retention of FPGS intron 8 (8PR) as a prominent splice variant conferring FPGS dysfunction and decreased MTX polyglutamylation in acute lymphoblastic leukaemia. Here, we explored the association between FPGS 8PR levels and lack of MTX responsiveness in RA patients. Methods Thirty-six patients undergoing MTX treatment were enrolled from the Combinatie behandeling Reumatoide Artritis (COBRA)-light trial. RNA was isolated from blood samples at baseline, 13 weeks and 26 weeks of therapy, from patients in either COBRA-light (n = 21) or COBRA (n = 15) treatment arms. RT-qPCR analysis was used to assess RNA levels of FPGS 8PR over wild-type FPGS (8WT). Results In the COBRA-light treatment arm, higher baseline ratios of 8PR/8WT were significantly associated with higher 44-joint disease activity score (DAS44) at 13 and 26 weeks. Higher baseline ratios of 8PR/8WT also trended towards not obtaining low disease activity (DAS Conclusion This study is the first to associate alterations in FPGS pre-mRNA splicing levels with reduced responsiveness to MTX treatment in RA patients. Trial registration ISRCTN55552928.

Spondyloarthritis (SpA) is a chronic systemic rheumatic disease, the hallmark manifestation of which is inflammatory back pain, and may also involve peripheral joints. There have been important developments in SpA, from its classification to the available imaging modalities, treatment options, and outcome measures. There has been a shift in the treatment paradigm to a more treat-to-target approach, where a level of a relevant outcome of the disease (e.g., disease activity) is defined as a goal to prevent consequent disability.1 The past typical example of a patient with SpA was a young person with irreversible deformation and functional disability that occurred over several years. Nowadays, the typical example of a patient with SpA is someone with a chronic but manageable disease who can remain active and participative. The reality is less ideal, since mandatory steps for a successful management (early recognition, referral, and treatment) are still undervalued. This review approaches the major ‘checkpoints’ that enable prompt and correct diagnosis and management of SpA.

Traditional management of patients with Crohn's disease includes symptoms and quality of life improvement. With the advent of biological agents, mucosal healing has become an achievable goal, documented through endoscopy. However, due to the transmural nature of inflammation, the prevention of bowel damage should be included in the aims of a targeted therapeutic strategy.Updated literature has been searched in PubMed from 2008 to 2020. This review focuses on the state of the art in the innovative therapeutic goals in Crohn's disease, also considering still controversial aspects and future research topics in the management of Crohn's disease.Although a widely agreed view supports the notion that mucosal healing and bowel damage control may promote beneficial outcomes (i.e. reduction in hospitalization and surgical rates, avoidance of steroids), long-term robust data are still missing. On the other hand, the development of -omics techniques has expanded our knowledge of the pathogenetic mechanism underlying inflammatory bowel disease and opened up new horizons in precision or personalized medicine.

Fecal calprotectin has been widely studied in inflammatory bowel disease (IBD) under clinical and therapeutic settings. It showed a good correlation with clinical, endoscopic, and histologic findings. For these reasons, fecal calprotectin is currently one of the most useful tools in IBD care, both in diagnosis and in clinical management. The development of biologic drugs allowed a deeper control of disease, which sometimes reaches histological healing; this is associated with a reduced risk of relapses and complications. The management of IBD treatment is currently carried out with a treat-to-target approach, and mucosal healing is considered at present to be the optimal therapeutic target, but the future is going through histologic remission. Fecal calprotectin is probably the best marker of mucosal healing, but it is correlated also with histologic remission: moreover, it has been recently studied as a possible therapeutic target in the CALM study. We carried out a comprehensive literature review in order to evaluate the role of fecal calprotectin at present and in the future in the management of IBD therapies.

Psoriatic arthritis (PsA) is a complex inflammatory musculoskeletal and skin disease. The treatment of PsA has changed substantially over the past 10 years. Clinical practice guidelines are developed to help busy clinicians rapidly integrate evolving knowledge of therapeutic management into practice. In this review, we compare PsA treatment recommendations or guidelines developed by one national organization [ACR and National Psoriasis Foundation (NPF) in 2018], one regional organization (EULAR in 2015), and one international organization (the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis in 2015). We examine the development of guidelines in PsA more broadly and examine similarities and differences in the three sets of recommendations.

Background and aimsDespite increasing interest in histologic remission as a treatment target in ulcerative colitis (UC), the accuracy of histologic findings in left colon in detecting pancolonic histologic remission is unknown.MethodsIn a retrospective cohort study of patients with endoscopically active pancolitis undergoing treat-to-target interventions, we evaluated the diagnostic accuracy of left-sided (distal to splenic flexure) histologic and endoscopic findings on colonoscopy for detecting histologic and endoscopic healing elsewhere in the colon.ResultsOf 86 patients with moderate to severely active pancolitis who underwent 2 consecutive colonoscopies during treat-to-target interventions, 38% and 51% achieved histologic and endoscopic remission, respectively. Substantial agreement (kappa, 0.67; 95% confidence interval (CI), 0.51-0.83) was observed in histologic findings between left and right colon on follow-up colonoscopy. Histologic, and endoscopic, findings in left colon showed excellent accuracy in detecting pancolonic histologic remission (area under the curve (AUC), 0.96 [95% CI, 0.93-1.0]; misclassification rate, 5.9%), histologic normalization (AUC, 1.0, 0%), endoscopic improvement (AUC, 0.95 [0.96-1.0], 3.5%) and endoscopic remission (AUC, 0.98 [0.96-1.00], 5.8%), respectively.ConclusionsIn patients with active pancolitis undergoing treat-to-target interventions, histologic and endoscopic findings in the left colon on colonoscopy have excellent accuracy for detecting pancolonic histologic remission, histologic normalization, endoscopic improvement, and endoscopic remission. Flexible sigmoidoscopy may suffice for monitoring histologic and endoscopic activity in patients with pancolitis.

Kidney involvement, termed lupus nephritis (LN), develops in 35–60% of patients with systemic lupus erythematosus, often early during the disease course. When not treated promptly and efficiently, LN may lead to rapid and severe loss of kidney function, being the reason why it is considered one of the most severe lupus manifestations. Despite improved pharmacotherapy, 5–20% of LN patients develop end-stage kidney disease within ten years from the LN diagnosis. While the principal ground of LN therapy is prevention of renal function worsening, resembling a race against nephron loss, consensual agreement upon outcome measures and clinically meaningful short- and long-term targets of LN therapy have yet to be determined. Literature points to the importance of inclusion of tissue-based approaches in the determination of those targets, and evidence accumulates regarding the importance of per-protocol repeat kidney biopsies in the evaluation of the initial phase of therapy and prediction of long-term renal prognosis. The latter leads to the hypothesis that the information gleaned from repeat biopsies may contribute to optimised therapeutic decision making, and, therefore, increased probability to attain complete renal response in the short term, and a more favourable renal prognosis within a longer prospect. The multinational project ReBioLup was recently designed to serve as a key contributor to form evidence about the role of per-protocol repeat biopsies in a randomised fashion and aspires to unify the global LN community towards improved kidney and patient survival.

ObjectivesTo provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.MethodsAn international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.ResultsThe task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.ConclusionsThese updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

In recent years, there has been a critical change in treatment paradigms in inflammatory bowel diseases (IBD) triggered by the arrival of new effective treatments aiming to prevent disease progression, bowel damage and disability. The insufficiency of symptomatic disease control and the well-known discordance between symptoms and objective measures of disease activity lead to the need of reviewing conventional treatment algorithms and developing new concepts of optimal therapeutic strategy. The treat-to-target strategies, defined by the selecting therapeutic targets in inflammatory bowel disease consensus recommendation, move away from only symptomatic disease control and support targeting composite therapeutic endpoints (clinical and endoscopical remission) and timely assessment. Emerging data suggest that early therapy using a treat-to-target approach and an algorithmic therapy escalation using regular disease monitoring by clinical and biochemical markers (fecal calprotectin and C-reactive protein) leads to improved outcomes. This review aims to present the emerging strategies and supporting evidence in the current therapeutic paradigm of IBD including the concepts of “early intervention”, “treat-to-target” and “tight control” strategies. We also discuss the real-word experience and applicability of these new strategies and give an overview on the future perspectives and areas in need of further research and potential improvement regarding treatment targets and (“tight”) disease monitoring strategies.

Background Crohn's disease (CD) can affect the entire gastrointestinal tract. Proximal small bowel (SB) lesions are associated with a significant risk of stricturing disease and multiple abdominal surgeries. The assessment of SB in patients with CD is therefore necessary because it may have a significant impact on prognosis with potential therapeutic implications. Because of the weak correlation that exists between symptoms and endoscopic disease activity, the "treat-to-target" paradigm has been developed, and the associated treatment goal is to achieve and maintain deep remission, encompassing both clinical and endoscopic remission. Small bowel capsule endoscopy (SBCE) allows to visualize the mucosal surface of the entire SB. At that time, there is no recommendation regarding the use of SBCE during follow-up. Aim To investigate the impact of SBCE in a treat-to-target strategy in patients with CD. Methods An electronic literature search was conducted in PubMed and Cochrane library using the following search terms: "capsule endoscopy", in combination with "Crohn's disease" and "treat-to-target" or synonyms. Two authors independently reviewed titles and abstracts identified by the search strategy after duplicates were removed. Following the initial screening of abstracts, all articles containing information about SBCE in the context of treat-to-target strategy in patients with CD were included. Full-text articles were retrieved, reference lists were screened manually to identify additional studies. Results Forty-seven articles were included in this review. Two indexes are currently used to quantify disease activity using SBCE, and there is good correlation between them. SBCE was shown to be useful for disease reclassification in patients who are suspected of having or who are diagnosed with CD, with a significant incremental diagnostic yield compared to other diagnostic modalities. Nine studies also demonstrated that the mucosal healing can be evaluated by SBCE to monitor the effect of medical treatment in patients with CD. This review also demonstrated that SBCE can detect post-operative recurrence to a similar extent as ileocolonoscopy, and proximal SB lesions that are beyond the reach of the colonoscope in over half of the patients. Conclusion SBCE could be incorporated in the treat-to-target algorithm for patients with CD. Randomized controlled trials are required to confirm its usefulness and reliability in this indication.

Background: In a context of therapeutic inertia, the French Society of Rheumatology (SFR) published its first recommendations on gout in 2020, which were deliberately simple and concise. The objectives of the study were to determine the profile of patients referred to French gout-expert centres, and to examine the results of their management and the factors leading to those results. Methods: Three hundred patients attending a first visit for gout management in three French referral centres were retrospectively and randomly included in this multicentre observational study. Visits were performed at baseline (M0) and scheduled for month 6 (M6), month 12 (M12), and month 24 (M24). Results: Patients were 81% male and had a mean age 62.2 ± 15.2 years. Management followed French recommendations after the baseline visit in 94.9% of cases. SU levels were below 6.0 mg/dL in 59.4% of patients at M6, 67.9% at M12, and 78.6% at M24, with increasing clinical improvement (i.e., flare decrease) over 2 years of follow-up. At M24, 50% of patients were treated with allopurinol (313 ± 105 mg/d), which exceeded renal restrictions of doses in 61.5% of them, and 48.2% received febuxostat (84 ± 36 mg/d). The need for a sufficient dosage of ULT was the only predictive factor found for successful achievement of SU levels < 6.0 mg/dL at a given visit. Conclusions: Simple application of gout-management guidelines is feasible in clinical practice and is efficient, with a majority of patients achieving SU targets and clinical improvement.

Objective To investigate the frequency and determinants of achieving the lupus low disease activity state (LLDAS), and the effect of LLDAS attainment on disease flare and damage accrual in a prospective, single-center cohort of Chinese lupus patients. Methods Baseline and follow-up data from consecutive patients at the Peking University First Hospital were collected from January 2017 to June 2020. Results A total of 185 patients were enrolled, with median (range) disease duration at enrolment of 2.3 (0.8–7.7) years, and median follow-up of 2.2 (1.0–2.9) years. By the end of the study, 139 (75.1%) patients had achieved LLDAS at least once; 82 (44.3%) patients achieved LLDAS for ≥ 50% of observations. Multivariable logistic regression analysis showed that 24-h urinary total protein (UTP; per g) (OR = 0.447, 95%CI [0.207–0.968], p = 0.041), serum creatinine (Scr; per 10 µmol/L) (OR = 0.72, 95%CI [0.52–0.99], p = 0.040), and C3 level (per 100 mg/L) (OR = 1.60, 95%CI [1.18–2.17], p = 0.003) at recruitment had independent negative associations with achieving LLDAS for ≥ 50% of observations. Kaplan–Meier analyses showed a significant reduction in flare rate with increased proportion of time in LLDAS. Attainment of LLDAS in at least 50% of observations was an independent protective factor for damage accrual (OR = 0.19, 95%CI [0.04–0.99], p = 0.049). Conclusions In this prospective Chinese cohort, LLDAS was an attainable goal in clinical practice. Nephritis-related markers (UTP and Scr) and C3 level at recruitment negatively influenced achievement of LLDAS. LLDAS achievement was significantly protective from flare and damage accrual. Key points • Low disease activity status (LLDAS) is an achievable target during SLE treatment in China. Urine protein, serum creatinine, and C3 level at recruitment independently affect LLDAS achievement in this group of Chinese lupus patients. • As a treatment target, LLDAS achievement has a highly protective effect for preventing flare and damage accrual, especially in case of achieving LLDAS for ≥ 50% of observations. • The present results further highlight the practical significance of treat-to-target principle in SLE management (T2T/SLE) and the needs for promoting the application of T2T/SLE in clinical practice as well as exploring the concrete implement strategy.

Atopic dermatitis (AD) is a chronically relapsing skin disease. Although a definitive cure is not available, appropriate treatment can control the disease. The advent of biologic drugs has led to the need for a clear definition of the disease severity and treatment response. A standardized list of outcomes that defines clinician-reported disease severity and patients' reported severity are therefore essential. Solid criteria to define the response to treatment and treatment failure are lacking to date.This systematic review defines treatment goals in terms of clinician-reported disease severity and patient-reported outcomes, referring to the published moderate-to-severe AD clinical trials. The application of these goals in daily clinical practice will ensure a better selection of available treatment options, thus increasing patient quality of care.A systematic literature search was performed to identify the treatments goals of randomized controlled clinical trials (RCTs) on moderate-to-severe adult AD published between January 2000 and October 2020.In total, 14 studies met the eligibility criteria. The most widely used tools in terms of clinician-reported disease severity were the Scoring of Atopic Dermatitis (SCORAD) followed by the Eczema Area Severity Score (EASI) and Investigator Global Assessment (IGA). For disease severity scales as efficacy outcome in RCTs, the greatest standardization and reproducibility was for improvement of at least 50% in EASI score and IGA score reduction of ≥2 grades from baseline. The most widely used tools from the patients' perspective were the Dermatology Life Quality Index (DLQI), Numeric Rate Scale (NRS)-itch and Patient Oriented Eczema Measure Score (POEM). In terms of patients' reported efficacy outcomes in RCTs, a numerical DLQI, NRS-itch and POEM score improvement of at least 4 points from baseline was reported.This systematic review highlights the need for collaboration between experts in order to define and optimize treatment outcomes. Despite considerable progress in harmonizing outcome measures, promoted by the foundation of the Harmonizing Outcome Measures for Eczema (HOME) initiative in 2008, our results demonstrate that this endpoint is still an unmet need. Based on the literature data we propose a minimum treatment goal algorithm for use in daily clinical practice aimed at stimulating a discussion on how the care of AD patients could be further improved.

Background The Tight Control of psoriatic arthritis (TICOPA) trial confirmed improved clinical outcomes with a treat to target (T2T) strategy in psoriatic arthritis (PsA). This consisted of 4-weekly review and escalation of ‘step up’ therapy (single disease modifying therapy (DMARD), combination DMARDs and then biologics) based on remission criteria. Based on this, a T2T approach is supported by European PsA treatment recommendations. However, it is not commonly implemented in routine care primarily due to feasibility and cost concerns. In the TICOPA trial, the same treatment regime was used for all participants regardless of their disease profile. Despite the recognition of PsA as a highly heterogeneous condition, no studies have tailored which drugs are used depending on disease severity. The cohort will establish real world outcomes for the T2T approach in PsA and also form the basis of a trials within cohorts (TWiCs) design to test alternative therapeutic approaches within embedded clinical trials providing an evidence base for treatment strategy in PsA. Methods The Multicentre Observational Initiative in Treat to target Outcomes in Psoriatic Arthritis (MONITOR-PsA) cohort will apply a T2T approach within routine care. It will recruit newly diagnosed adult patients with PsA starting systemic therapies. The cohort is observational allowing routine therapeutic care within NHS clinics but a T2T approach will be supported when monitoring treatment within the cohort. Eligible participants will be adults (≥18 years) with active PsA with ≥ 1 tender or swollen joints or enthesis who have not previously had treatment with DMARDs for articular disease. Discussion This study is the first TWiC designed to support a fully powered randomised drug trial. The results from the observational cohort will be compared with those observed in the TICOPA trial investigating the clinical effectiveness and health care costs of the pragmatic T2T approach. Nested trials will provide definitive RCT evidence establishing the optimal management of PsA within the T2T approach. The TWiCs design allows robust generalizability to routine healthcare, avoids disappointment bias, aids recruitment and in future will allow assessment of longer-term outcomes. Trial registration ClinicalTrials.gov NCT03531073. Retrospectively registered on 21 May 2018.

Background Subclinical synovitis by ultrasound is a frequent finding in rheumatoid arthritis (RA) patients in remission and has been shown to be related to erosive progression, risk of flare and unsuccessful drug tapering, but it has not been investigated how a DAS28 T2T-steered strategy in routine care affects the presence of subclinical synovitis in RA patients in remission. The aim of the current study was to investigate the presence of ultrasound-detected subclinical inflammation in RA patients in long-term remission receiving either biological or conventional disease-modifying anti-rheumatic drugs (bDMARD/csDMARD) and, finally, to investigate the presence of ultrasound remission using different ultrasound remission criteria. Methods Eighty-seven RA patients (42 patients receiving bDMARD and 45 csDMARD) received DAS28-CRP-steered treatment in routine care and had achieved DAS28-CRP-remission for > 1 year without radiographic progression. Twenty-four joints were scored 0–3 by ultrasound (elbows, wrists, knees, ankles, metacarpophalangeal and metatarsophalangeal joints 2–5) for grey-scale synovial hypertrophy (GS) and colour Doppler activity (CD) using the OMERACT scoring system. Ultrasound remission was defined as strict (GS score = 0 and CD score = 0), semi-strict (GS score < 1 and Doppler score = 0) and Doppler remission (Doppler score = 0). Results No differences between treatment groups were found for GS sum score and Doppler sum score (median (range) 6 (0–19) and 0 (0–12), respectively). A Doppler score > 0 in at least 1 joint was seen in 44%, a GS score > 1 in at least 1 joint in 93% and a GS score > 2 in at least 1 joint in 54% of patients. Strict ultrasound remission was only observed in bDMARD patients (7%; p = 0.01). Thirty-seven per cent were in semi-strict ultrasound remission and 56% in Doppler remission (no significant difference between groups) with similar results across the subgroups of patients who also fulfilled the ACR-EULAR Boolean-, CDAI- and SDAI-remission criteria. Conclusions Ultrasound frequently detected subclinical synovitis in RA patients in longstanding DAS28-remission obtained through a DAS28-CRP-steered strategy. This was independent of treatment and applied ultrasound remission criteria. Strict ultrasound remission was rare.

Currently no treat-to-target framework to guide systemic treatment in adults with moderate-to-severe atopic dermatitis exists. We sought to reach international consensus through an eDelphi process on a core set of recommendations for such an approach. Recommendations were developed by an international Steerng Committee, spanning 3 areas (Guiding Principles, Decision Making, and Outcome Thresholds) and 2 specific time-points; an initial acceptable target at 3 months and an optimal target at 6 months, each based on improvements in patient global assessment plus at least one specific outcome domain. These treat-to-target-orientated recommendations were evaluated by an extended international panel of physicians, nurses and patients. Proposed recommendations were rated using a 9-point Likert scale; for each recommendation, consensus agreement was reached if >= 75% of all respondents rated agreement as >= 7. Consensus on 16 core recommendations was reached over 2 eDelphi rounds. These provide a framework for shared decision-making on systemic treatment continuation, modification, or discontinuation.

Currently no treat-to-target framework to guide systemic treatment in adults with moderate-to-severe atopic dermatitis exists. We sought to reach international consensus through an eDelphi process on a core set of recommendations for such an approach. Recommendations were developed by an international Steering Committee, spanning 3 areas (Guiding Principles, Decision Making, and Outcome Thresholds) and 2 specific time-points; an initial acceptable target at 3 months and an optimal target at 6 months, each based on improvements in patient global assessment plus at least one specific outcome domain. These treat-to-target- orientated recommendations were evaluated by an extended international panel of physicians, nurses and patients. Proposed recommendations were rated using a 9-point Likert scale; for each recommendation, consensus agreement was reached if ≥ 75% of all respondents rated agreement as ≥ 7. Consensus on 16 core recommendations was reached over 2 eDelphi rounds. These provide a framework for shared decision-making on systemic treatment continuation, modification, or discontinuation.

Background & aimsClinical remission, defined by a composite of patient reported outcomes and Mayo endoscopy subscore (MES) 0 or 1 is a recommended treatment target in patients with ulcerative colitis (UC). We estimated whether incorporating more rigorous remission definitions, of endoscopic remission (MES 0) and histologic remission, affects risk of relapse.MethodsThrough a systematic review, we identified cohort studies in adults with UC in clinical remission that reported a minimum 12-month risk of clinical relapse, based on MES (0 vs 1) and/or histologic disease activity, in patients with endoscopic remission. Using random effects meta-analysis, we calculated relative and absolute risk of clinical relapse in patients with UC achieving different treatment targets.ResultsIn a meta-analysis of 17 studies that included 2608 patients with UC in clinical remission, compared to patients achieving MES 1, patients achieving MES 0 had a 52% lower risk of clinical relapse (relative risk, 0.48; 95% CI, 0.37-0.62). The median 12-month risk of clinical relapse in patients with MES 1 was 28.7%; the estimated annual risk of clinical relapse in patients with MES 0 was 13.7% (95% CI, 10.6-17.9). In a meta-analysis of 10 studies in patients in endoscopic remission (MES 0), patients who achieved histologic remission had a 63% lower risk of clinical relapse vs patients with persistent histologic activity (relative risk, 0.37; 95% CI, 0.24-0.56). Estimated annual risk of clinical relapse in who achieved achieving histologic remission was 5.0% (95% CI, 3.3-7.7).ConclusionsIn a systematic review and meta-analysis of patients with UC in clinical remission, we observed that patients achieving more rigorous treatment endpoints (endoscopic and histologic remission) have a substantially lower risk of clinical relapse compared with patients achieving clinical remission.

BackgroundTreat-to-target (T2T) is a widely accepted strategy for patients with rheumatoid arthritis (RA). It recommends attaining a goal of at least low disease activity (LDA) within 6 months; otherwise, the current therapy should be modified. We aimed to investigate whether switching a first-line targeted therapy (TT) in patients not reaching LDA within 6 months leads to a higher probability of meeting LDA at the 12-month visit in daily clinical practice using data from Czech registry ATTRA.MethodsWe included patients with RA starting the first-line TT from 1 January 2012 to 31 January 2017 with at least 1-year follow-up. We created four mutually exclusive cohorts based on (1) switching to another TT within the first year and (2) reaching a treatment target (DAS28-ESR ≤ 3.2) at the 6-month visit. The primary outcome was the comparison of odds for reaching remission (REM) or LDA at the 12-month visit between patients switching and not switching TT after not reaching treatment target at 6 months. Before using logistic regression to estimate the odds ratio, we employed the propensity score to match patients at the 6-month visit.ResultsA total of 1275 patients were eligible for the analysis. Sixty-two patients switched within the first 5 months of the treatment before evaluating treatment response at the 6-month visit (C1); 598 patients reached the treatment target within 6 months of therapy (C2); 124 patients did not reach treatment response at 6-month visit and switched to another therapy (C3), and 491 patients continued with the same treatment despite not reaching LDA at the 6-month visit (C4). We matched 75 patients from cohort C3 and 75 patients from C4 using the propensity score. Patients following the T2T principle (C3) showed 2.8 (95% CI 1.4–5.8;p = 0.005) times increased likelihood of achieving REM/LDA at the 12-month visit compared to patients not following the T2T strategy (C4).ConclusionsIn daily clinical practice, the application of the T2T strategy is underused. Switching TT after not reaching REM/LDA within the first 6 months leads to a higher probability of achieving REM/LDA in RA patients at the 12-month visit.

Background:The need for immune suppressive strategies in the control of chronic inflammatory bowel diseases originated in the 1960s following the perception of a relative inefficacy of salazopyrin and its derivatives. In some 50 years upon an anecdotal claim, the indication for thiopurines in the management of inflammatory bowel diseases has come of age.Objective:The aim of this minireview is to give an overview, after the historical premises, of the current use of thiopurines in the context of inflammatory bowel diseases.Method:Through MEDLINE searches, we reviewed the literature of the last two decades.Results:For Crohn’s disease, the 1980 trial of 6-mercaptopurine for steroid sparing and fistula closure proved pivotal. The analysis of withdrawal experiments and of numerous open trials has established the efficacy of thiopurines for ulcerative colitis. In this indication, cutting-edge data are now showing that because targeting dysplasia, thiopurines can induce mucosal/histological healing, thus abolishing or delaying the need for pre-emptive (tumor prophylactic) colectomy.Conclusion:In UC thiopurines may be recognized to effect a treat-to-target strategy, joining the modern algorithms of rheumatologic disorders.

Inflammatory bowel disease (IBD) is a lifelong, progressive disease that has disabling impacts on patient's lives. Given the complex nature of the diagnosis of IBD and its management there is consequently a large economic burden seen across all health care systems. Quality indicators (QI) have been created to assess the different façades of disease management including structure, process and outcome components. Their development serves to provide a means to target and measure quality of care (QoC). Multiple different QI sets have been published in IBD, but all serve the same purpose of trying to achieve a standard of care that can be attained on a national and international level, since there is still a major variation in clinical practice. There have been many recent innovative developments that aim to improve QoC in IBD including telemedicine, home biomarker assessment and rapid access clinics. These are some of the novel advancements that have been shown to have great potential at improving QoC, while offloading some of the burden that IBD can have vis-a-vis emergency room visits and hospital admissions. The aim of the current review is to summarize and discuss available QI sets and recent developments in IBD care including telemedicine, and to give insight into how the utilization of these tools could benefit the QoC of IBD patients. Additionally, a treating-to-target structure as well as evidence surrounding aggressive management directed at tighter disease control will be presented.

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a real-world setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo- controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p

Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory condition of the gastrointestinal tract causing bowel damage, hospitalizations, surgeries, and disability. Although there has been much progress in the manage ment of IBD with established and evolving therapies, most current approaches have failed to change the natural course. Therefore, the treatment approach and follow-up of patients with IBD have undergone a significant change. Usage of im munosuppressants and/or biologics early during the course of the disease, known as top-down or accelerated step-up approach, was shown to be superior to conven tional management in patients who had been recently diagnosed with IBD. This approach can be applied to selected groups based on prognostic factors to control disease activity and prevent progressive disease. Therapeutic targets have been shifted from clinical remission mainly based on symptoms to objective parame ters such as endoscopic healing due to the discrepancies observed between symp toms, objectively evaluated inflammatory activity, and intestinal damage. The concept of treat-to-target in IBD has been supported by population-based cohort studies, post hoc analysis of clinical trials, and meta-analysis, but more evidence is needed to support this concept to be applied to the clinical practice. In addition, individualized approach with tight monitoring of non-invasive biomarker such as C-reactive protein and fecal calprotectin and drug concentration has shown to improve clinical and endoscopic outcomes. An appropriate de-escalation strategy is considered based on patient demographics, disease features, current disease status, and patients’ preferences.

Biologic therapy is still limited in lupus, where chronic steroid exposure and wide-spectrum immunosuppression are major triggers of organ damage. In this viewpoint, the authors summarize their views for a "half-full or half-empty" glass on targeted therapy in SLE. The are several reasons for seeing the glass half-empty and in this section the authors propose a critical reflection on scarceness of novel targeted lupus therapies. They show how hard it is to identify suitable biological and clinical targets and to choose the patients that may best fit those targets, as well as to stratify patients according to disease subtype and response, all contributing to the final outcome. On the other hand, reasons are emerging to see the glass half-full, including the growing evidence that disease activity and damage can both be hindered by the proper use of novel drugs and that promising molecules are upcoming. In this section, the authors contextualize potentials and failures of new drugs, providing a critical reading of disappointing results and underlining the concrete benefits obtainable through a wise use of available treatments. Indeed, combining medications with new therapeutic strategies such as the treat-to-target seems the right approach to add some water to a filling glass.

The aim of this study was to assess changes in the estimated glomerular filtration rate (eGFR) in gouty patients with chronic kidney disease (CKD) using a "treat-to-target" (T2T) approach in gout. This multicenter observational retrospective study included patients diagnosed with gout and CKD stage 3 taking xanthine oxidase inhibitors (XOIs) (allopurinol or febuxostat) for at least 12 months. All patients were treated using a T2T strategy according to national gout guidelines to achieve the target levels of serum uric acid (sUA; < 5-6 mg/dl) within 6 months of the first visit. The primary outcome was to assess changes in eGFR. The effects of independent variables were analyzed over eGFR in a linear mixed-effects (LME) model. Fifty patients with gout and CKD stage 3 treated with XOIs with a T2T strategy for 12 months were included. Eighty-two percent of the patients achieved the sUA target during the study period. The improvement seen in eGFR was higher during the first 6 months, showing a median increase of 7.54 ml/min/m(2) (SE = 1.25) and trending towards stability over 12 months. For every 1 mg/dl of decrease in sUA, an improvement of 1.5 ml/min/m(2) in eGFR was observed (coefficient +/- SE: - 1.58 +/- 0.26) (p < 0.001) with no differences between type and dosage of XOIs treatment, colchicine administration, age, sex, and smoking status. A reduction in sUA levels using a T2T approach with XOIs at an optimal dose is possible and could help conserve and improve renal function in gouty patients with CKD stage 3.

Monogenic Interleukin 1 (IL-1) mediated autoinflammatory diseases (AID) are rare, often severe illnesses of the innate immune system associated with constitutively increased secretion of pro-inflammatory cytokines. Clinical characteristics include recurrent fevers, inflammation of joints, skin, and serous membranes. CNS and eye inflammation can be seen. Characteristically, clinical symptoms are coupled with elevated inflammatory markers, such as C-reactive protein (CRP) and serum amyloid A (SAA). Typically, AID affect infants and children, but late-onset and atypical phenotypes are described. An in-depth understanding of autoinflammatory pathways and progress in molecular genetics has expanded the spectrum of AID. Increasing numbers of genetic variants with undetermined pathogenicity, somatic mosaicisms and phenotype variability make the diagnosis of AID challenging. AID should be diagnosed as early as possible to prevent organ damage. The diagnostic approach includes patient/family history, ethnicity, physical examination, specific functional testing and inflammatory markers (SAA, CRP) during, and in between flares. Genetic testing should be performed, when an AID is suspected. The selection of genetic tests is guided by clinical findings. Targeted and rapid treatment is crucial to reduce morbidity, mortality and psychosocial burden after an AID diagnosis. Management includes effective treat-to-target therapy and standardized, partnered monitoring of disease activity (e.g., AIDAI), organ damage (e.g., ADDI), patient/physician global assessment and health related quality of life. Optimal AID care in childhood mandates an interdisciplinary team approach. This review will summarize the current evidence of diagnosing and managing children with common monogenic IL-1 mediated AID.

Background Rare autoinflammatory diseases (AIDs) including Cryopyrin-Associated Periodic Syndrome (CAPS), Tumor Necrosis Receptor-Associated Periodic Syndrome (TRAPS) and Mevalonate Kinase Deficiency Syndrome (MKD)/ Hyper-IgD Syndrome (HIDS) are genetically defined and characterized by recurrent fever episodes and inflammatory organ manifestations. Early diagnosis and early start of effective therapies control the inflammation and prevent organ damage. The PRO-KIND initiative of the German Society of Pediatric Rheumatology (GKJR) aims to harmonize the diagnosis and management of children with rheumatic diseases nationally. The task of the PRO-KIND CAPS/TRAPS/MKD/HIDS working group was to develop evidence-based, consensus diagnosis and management protocols including the first AID treat-to-target strategies. Methods The national CAPS/TRAPS/MKD/HIDS expert working group was established, defined its aims and conducted a comprehensive literature review synthesising the recent (2013 to 2018) published evidence including all available recommendations for diagnosis and management. General and disease-specific statements were anchored in the 2015 SHARE recommendations. An iterative expert review process discussed, adapted and refined these statements. Ultimately the GKJR membership vetted the proposed consensus statements, agreement of 80% was mandatory for inclusion. The approved statements were integrated into three disease specific consensus treatment plans (CTPs). These were developed to enable the implementation of evidence-based, standardized care into clinical practice. Results The CAPS/TRAPS/MKD/HIDS expert working group of 12 German and Austrian paediatric rheumatologists completed the evidence synthesis and modified a total of 38 statements based on the SHARE recommendation framework. In iterative reviews 36 reached the mandatory agreement threshold of 80% in the final GKJR member survey. These included 9 overarching principles and 27 disease-specific statements (7 for CAPS, 11 TRAPS, 9 MKD/HIDS). A diagnostic algorithm was established based on the synthesized evidence. Statements were integrated into diagnosis- and disease activity specific treat-to-target CTPs for CAPS, TRAPS and MKD/HIDS. Conclusions The PRO-KIND CAPS/TRAPS/MKD/HIDS working group established the first evidence-based, actionable treat-to-target consensus treatment plans for three rare hereditary autoinflammatory diseases. These provide a path to a rapid evaluation, effective control of disease activity and tailored adjustment of therapies. Their implementation will decrease variation in care and optimize health outcomes for children with AID.

Celine J Van De Laar,1 Martijn AH Oude Voshaar,1,2 Walid KH Fakhouri,3 Liliana Zaremba-Pechmann,3 Francesco De Leonardis,3 Inmaculada De La Torre,3 Mart AFJ Van De Laar1,2 1Transparency in Healthcare BV, Hengelo, the Netherlands; 2Department of Psychology and Communication of Health and Risk, Institute for Behavioural Research, University of Twente, Enschede, the Netherlands; 3Eli Lilly & Company, Indianapolis, IN, USACorrespondence: Celine J Van De Laar Tel +31 74-43032645Email c.vandelaar@tihealthcare.nlBackground: Baricitinib is a janus kinase (JAK1/JAK2) inhibitor developed for the treatment of patients suffering from rheumatoid arthritis (RA). Treating RA to the target of remission is current common practice. Cost-effectiveness of different treat-to-target (T2T) strategies, especially ones including new treatments is important for development and preference policy for treatment centers. European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) guidelines are currently unclear about preference between a JAK1/JAK2 versus a biological disease-modifying antirheumatic drug (bDMARD).Objective: The main goal of this paper was to evaluate the cost-effectiveness of baricitinib versus first biological for methotrexate inadequate responders in a T2T strategy using a Markov model that incorporates hospital costs as well as societal costs. Costs and utilities over five years were compared between the two strategies.Methods: A Monte Carlo simulation model was developed to conduct cost–utility analysis from the societal perspective over 5 years. Health states were based on the DAS28-erythrocyte sedimentation rate (ESR) categories. Effectiveness of baricitinib was retrieved from randomized controlled trials. Effectiveness of all other treatments, health state utilities, medical costs, and productivity loss were retrieved from the Dutch RhEumatoid Arthritis Monitoring (DREAM) cohorts. Annual discount rates of 1.5% for utility and 4% for costs were used. Probabilistic sensitivity analysis was employed to incorporate uncertainty and assess robustness of the results.Results: Probabilistic sensitivity analysis results showed the baricitinib strategy yielded lower costs and higher utility over a 5-year period. Scenario analyses showed the baricitinib strategy to be cost-effective in both the moderate and severe RA populations.Conclusion: Results suggest that the use of a JAK1/JAK2 inhibitor instead of a bDMARD in a T2T approach is cost-effective in csDMARD refractory RA patients.Keywords: Markov model, rheumatoid arthritis, baricitinib, cost-effectiveness, health economic model, treat-to-target

Background The aim of this retrospective study was to examine the longitudinal association between disease activity and radiographic damage in a cohort of patients with early RA (symptom onset Methods Baseline to 3-year follow-up data were used from patients included in the DREAM remission induction cohort. Patients received protocolized T2T treatment, aimed at 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR) remission. Disease activity (DAS28-ESR and C-reactive protein, CRP) were assessed at least every 3 months; X-rays of the hand and feet at inclusion, 6 months, and 1, 2, and 3 years were scored using modified Sharp/van der Heijde scoring (SHS). Between and within-person associations between time-integrated disease activity and radiographic progression over time were examined. Results A subset of 229 out of 534 included patients were available for analysis. At the between-patient level, time-integrated DAS28-ESR scores were not significantly correlated with progression at the 6 month and 2-year follow-up and only weakly at the 1-year (Pearson’s correlation coefficient r = 0.17, P r = 0.21, P r between 0.39 and 0.59; P values Conclusions In early RA patients treated according to T2T, radiographic progression appears to be an individually determined disease process, driven by factors other than consistent high disease activity. For individual patients, the intra-patient relation between disease activity and cumulative radiographic damage during the first 6 months is a good indicator for this relation in later years. Trial registration Netherlands Trial Register NTR578, 12 January 2006.

Treat-to-target (T2T) and dose tapering after obtaining the therapeutic objective (called “treat-to-budget”-T2B-in this Commentary) are the two most commonly used therapeutic strategies in rheumatoid arthritis. In theory, both strategies could add value to the healthcare system, although they are focused on different objectives: T2T strategy improves outcomes but increases short-term costs, while the cost savings obtained through T2B are associated with higher relapse rates. The systematic implementation of both strategies must be founded on solid evidence of their effectiveness and efficiency. However, the level of evidence between guidelines and individual studies is inconsistent for both strategies and the number and the quality of cost-effectiveness analyses is scarce. Raising the level of evidence requires a move from generalization to individualization by conducting randomized clinical trials that assess each of the many strategies that fall under the umbrella of the overall T2T and T2B concepts. In addition, such studies should consider the therapeutic goals and impact of the disease from the perspective of individual patients, which is only possible by promoting shared decision-making, Fee were funded by Lilly Spain

IntroductionRheumatoid arthritis (RA) is a chronic systemic disease and one of the most disabling diseases for patients. The American College of Rheumatology (ACR) issued a new guideline in 2015 for the treatment of RA based on the treat-to-target strategy to achieve better outcomes. This study will focus on the real-world rates of remission and low disease activity of patients with early RA in China, who will be treated according to the 2015 ACR guideline. Additionally, factors influencing treat-to-target outcomes will be analysed, and long-term prognosis and quality of life will be assessed.Method and analysisTwo-hundred patients with early RA will be enrolled, treated and followed up once every 3 months for 48 months. These patients should fulfil the 2010 RA classification criteria of the ACR/European League Against Rheumatism with a disease course of no more than 6 months and should also fulfil other eligibility criteria. The patients will be treated following the 2015 ACR guideline. Their disease activity will be assessed, and they will be instructed to complete several questionnaires once every 3 months. The primary outcomes are the Disease Activity Score on 28 joints and Health Assessment Questionnaire Disability Index. The secondary outcome variables are the Simplified Disease Activity Index, Clinical Disease Activity Index and Routine Assessment of Patient Index Data 3 results, imaging data and personal medical costs. The data will be analysed using appropriate statistical analyses.Ethics and disseminationThis research was approved by the Nanfang Hospital Ethics Committee (NFEC-2017–192). The results of the study will be published in international peer-reviewed journals.Trial registration numberNCT03508713; Pre-results.

Peter C Taylor,1 Rieke Alten,2 Juan J Gomez Reino,3 Roberto Caporali,4 Philippe Bertin,5 Emma Sullivan,6 Robert Wood,6 James Piercy,6 Radu Vasilescu,7 Dean Spurden,8 Jose Alvir,9 Miriam Tarallo10 1Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; 2Department of Internal Medicine II, Rheumatology, Clinical Immunology, and Osteology, Schlosspark Klinik, University Medicine Berlin, Berlin, Germany; 3Experimental and Observational Rheumatology and Rheumatology Unit, Fundacion Ramon Dominguez and Rheumatology, Hospital Clinico Universitario, Santiago de Compostela, Spain; 4Division of Rheumatology, IRCCS Foundation Policlinico S. Matteo, University of Pavia, Pavia, Italy; 5Service de Rhumatologie, CHU Dupuytren, Limoges, France; 6Real-World Evidence and Epidemiology, Adelphi Real World, Bollington, UK; 7Medical Affairs, International Developed Markets, Pfizer, Brussels, Belgium; 8Health Economics and Outcomes Research, Pfizer Ltd, Tadworth, UK; 9Statistical Research and Data Science Center, Global Product Development, Pfizer Inc, New York, NY, USA; 10Patient and Health Impact, Pfizer Italia Srl, Rome, Italy Objective: The aim of this study was to identify factors that influence treatment adjustments and adoption of a treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA) in European practices.Methods: Cross-sectional data were drawn from the Adelphi 2014 RA Disease Specific Programme. Treatment patterns and clinical characteristics were investigated in patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) vs non-bDMARDs. For the T2T analysis, patients were subdivided into two subsets (RA diagnosis

Objective To analyse changes over tune in the treatment with disease modifying anti-rheumatic drugs and biological therapies prescribed to patients from an early arthritis register and whether these changes had an impact on their outcome. Methods This was a longitudinal retrospective 2-year study based on data collected in the PEARL study. The population was clustered in three groups depending on year of symptoms onset (2000-2004, 2005-2009, 2010-2014). Intensity of disease- modifying anti-rheumatic drug treatment was calculated and the percentage of patients receiving biological therapy during the first 2-year follow-up was collected. Disease activity and remission at the end of follow-up, as well as radiological progression were the outcomes analysed. Multivariable analyses were fitted to determine which variables including the three period times were associated with the outcomes. Results A significant increase in treatment intensity was observed in patients with undifferentiated arthritis, getting closer to that prescribed to patients fulfilling the 1987 RA criteria at the last period studied (2010-2014). This finding was associated with a significantly higher percentage of patients in remission and lower progression of the erosion component of the Sharp van der Heijde score. Conclusion During the last 15 years, the treatment of patients with early arthritis in our hospital has been progressively increased and it has been associated with significantly better outcomes.

Treat-to-target recommendations provide physicians a useful strategy to reduce the probability of disease progression and in general to manage PsA patients. However, it could be difficult to apply in real life, since PsA is a very heterogeneous disease with different manifestations to be treated. In fact, depending on the patient's expectation, some aspects of the disease could be prominent or not, beyond the mere achievement of the target of remission or low-disease activity. In this context, the concept of a "target to treat" strategy should be taken in to account.

ObjectivesIn a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial (RCT) (MUSE [NCT01438489]) and then utilize LLDAS to discriminate between anifrolumab and placebo.MethodsPatients received intravenous placebo (n=102) or anifrolumab (300 mg, n=99; 1,000 mg, n=104) Q4W plus standard of care for 48 weeks. LLDAS attainment (SLE Disease Activity Index 2000 ≤4 without major organ activity, no new disease activity, Physician’s Global Assessment ≤1, prednisolone ≤7.5 mg/d and standard immunosuppressant dosage tolerance) was assessed. Associations with endpoints and LLDAS attainment differences between treatments were explored.ResultsLLDAS attainment at Week 52 was associated with SLE Responder Index 4 (SRI[4]) and British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) (74/85[87%] and 62/84[74%] were also SRI[4] and BICLA responders, respectively; both nominal pAnifrolumab-treated patients achieved earlier LLDAS, and more spent at least half their observed time in LLDAS (OR vs. placebo; 300 mg: 3.04, 95% CI 1.34 to 6.92, nominal p=0.008; 1,000 mg: 2.17, 95% CI 0.93 to 5.03, nominal p=0.072) vs placebo-treated patients. At Week 52, 17/102 (17%), 39/99 (39%) and 29/104 (28%) of patients on placebo, anifrolumab 300 and 1,000 mg, respectively, attained LLDAS (OR vs. placebo; 300 mg: 3.41, 95% CI 1.73 to 6.76, pConclusionsLLDAS attainment represents a clinically meaningful SLE outcome measure, and anifrolumab is associated with more patients who met LLDAS criteria versus placebo. These data support LLDAS as an SLE RCT endpoint.Trial registration numberNCT1438489; Post-results.

The National Psoriasis Foundation (NPF) is developing an agenda for patient-centered research to help patients and their caregivers make more informed health care decisions by engaging psoriasis patients in prioritizing comparative effectiveness research (CER) topics. The NPF has created a novel patient-centered research platform known as Citizen Pscientist (CP), allowing patients with psoriasis and psoriatic arthritis to register and contribute their health data. The CP Governance Council administered an online 23-question CER survey to the CP community and held a structured meeting on December 3, 2016, with patients and researchers to review CER survey results and discuss patient-centered research priorities. Of the 2,945 patients surveyed, 792 patients responded. Three CER topics were deemed to be of high priority for the research agenda: 1) Treat-to-target therapy for psoriasis, 2) Psoriatic arthritis screening questionnaires for early detection and treatment of psoriatic arthritis, and 3) Comparative effectiveness of home-based phototherapy for psoriasis.

The start of the new millennium is marked by a substantial progress in the development of rheumatology: pathogenesis of many rheumatic diseases (RDs) was more deeply studied; their diagnostic criteria validated; disease activity indices worked out; the concepts of remission and exacerbation introduced; much attention has been given to the investigations of quality of life in patients. The possibility of pharmacotherapy for immunoinflammatory RDs was extended by the advent of biological agents (BA). The treatment strategy for RDs was also changed. The treat-to-target concept was put forth for rheumatoid arthritis in 2010 and for ankylosing spondylitis later. The project of treat-to-target concept in systemic lupus erythematous (SLE) was launched on the initiative of the world’s leading rheumatologists in January 2013. The result of their work is the treat-to-target-in-SLE recommendations published in 2014 and formulated as 4 basic principles and 11 general recommendations. The purpose of this publication is to provide general characteristics of the basic provisions of the principles and recommendations with commentaries of leading experts discussing characteristics of SLE in the Russian Federation and some debatable and unsolved problems.

OBJECTIVES: To investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target. METHODS: RA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44

Objective In PsA, the treatment objective is remission or low disease activity (LDA), but patients’ perception of remission is poorly studied. This analysis aimed to identify factors associated with patient-defined remission. Methods This analysis uses ReFlaP data, an international PsA study, with remission defined as ‘At this time, is your psoriatic arthritis in remission, if this means: you feel your disease is as good as gone?’. Variables associated with, first, patient-defined remission and, second, LDA were identified using multivariable logistic regression and principal component analysis (PCA) to explore correlated variables. Results Of 424 patients (50.2% male, mean age 52 years) with established disease, 94 (22.2%) reported themselves as being in remission and 191 (45.0%) as LDA alone. In multivariable analysis pain, psoriasis, impact of disease, physician opinion of symptoms from joint damage and Groll comorbidity index were independent predictors of remission. For LDA, results were similar. Using PCA, variance explained was 74% by five components for men and 80% by six components for women. The key component from PCA for remission was, for both sex, disease impact (Psoriatic Arthritis Impact of Disease, pain and HAQ) explaining 22.2–27.5% of variance. Other factors included musculoskeletal disease activity, chronicity/joint damage, psoriasis, enthesitis and CRP. For LDA, similar factors were identified but the variance explained was lower (64–68%). Conclusion Many factors impact on patients’ opinion of remission, dominated by disease impact. Disease activity in multiple domains, chronicity/age, comorbidities and symptoms due to other conditions contribute to a robust model highlighting that patient-defined remission is multifaceted. Trials registration Clinicaltrials.gov, http://clinicaltrials.gov, NCT 03119805.