JAK inhibitors in the treatment of adult patients with juvenile idiopathic arthritis: a retrospective monocentric experience.

OBJECTIVES: This study aims to evaluate the efficacy and safety of JAK inhibitors (JAKi) in a monocentric cohort of adult patients with juvenile idiopathic arthritis (JIA). METHODS: Patients attending a rheumatology transition clinic were retrospectively included in case of: i) JIA diagnosis according to current classification criteria (1); ii) age ≥18 years and iii) treatment with JAKi for at least 3 months. RESULTS: Seventeen adult patients with JIA were treated with JAKi (as first JAKi, 9 patients (52.9%) received tofacitinib and 8 (47.1%) baricitinib). At 3 months after JAKi initiation, 8 patients (47%) achieved a response and 4 patients (23.5%) achieved disease remission (3 patients with baricitinib and 1 with tofacitinib, 37.5% vs. 16.7%, p=0.294). None of those with systemic JIA and enthesitis-related arthritis obtained remission; the remission rate at 3 months was higher, although not significantly, in the oligoarticular subset compared to the polyarticular subset (37.5% vs. 20%). Patients with ≤1 active joint involvement at JAKi start had a higher remission rate (50% vs. 22.2%). Subjects who achieved remission on JAKi had a significantly lower pre-treatment DAS28-CRP compared to those with still active disease (p=0.010, Mann-Whitney U=4). A pre-treatment DAS28-CRP <3.76 predicted response to JAKi with 100% sensitivity and 84.6% specificity (p=0.023). The remission rate was lower among patients who had been treated with ≥2 biological drugs before JAKi start (9% vs. 66.7%; p=0.05). One patient in concomitant treatment with leflunomide developed severe arterial hypertension. CONCLUSIONS: JAKi may represent an effective and safe treatment option for adult JIA patients with low/moderate disease activity, particularly in case of oligoarticular involvement.

Insights into the clinical presentation of juvenile systemic lupus erythematosus: the PRAGMA monocentric cohort of 177 patients.

OBJECTIVES: The aim of this work is to describe the clinical manifestations at onset and during follow-up in a monocentric cohort of patients with juvenile systemic lupus erythematosus (jSLE) from the Paediatric Rheumatology group of the Milan area (PRAGMA). METHODS: Patients were retrospectively included in case of i) SLE diagnosis according to the 1997 American College of Rheumatology or the 2012 SLICC classification criteria and ii) disease onset before 18 years. RESULTS: Among the 177 recruited patients (155 females), haematologic involvement was the most common disease manifestation (75%), followed by joint and cutaneous involvements (70% and 57%, respectively). Renal disease was observed in 58 patients (32.8%), neurological complications in 26 cases (14.7%). Patients presented most commonly 3 clinical manifestations (32.8%), while 2 organ involvements were identified in 54 patients (30.5%) and 4 in 25 subjects (14.1%). The 49 patients with disease onset <10 years had less commonly articular involvement (p=0.02), while patients aged >14.8 years displayed less neurological manifestations (p=0.02). At a median follow-up of 118 month, the disease progressed in 93 patients, with a median of 2 new manifestations per patient. Low complement at diagnosis predicted new clinical manifestations (p=0.013 for C3 and p=0.0004 for C4). The median SLEDAI at diagnosis was 13; SLEDAI was substantially similar at 6 months, decreased at 12 months to remain stable at 18 months and further reduce at 24 months (p<0.0001). CONCLUSIONS: These data from a large jSLE monocentric cohort allow gaining further insights into a rare disease with a still high morbidity burden.

Anti-SARS-CoV-2 vaccination in adolescent and adult patients with juvenile-onset systemic lupus erythematosus: tolerability and impact on disease activity.

OBJECTIVES: JSLE has a severe presentation and a remitting course. Patients with JSLE carry an increased vulnerability to infections, which also act as triggers of disease flare. Thus, vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important tool in JSLE. The objective of this study is to evaluate the tolerability and the safety of anti-SARS-CoV-2 vaccination, including the booster, in a monocentric cohort of JSLE patients. METHODS: Clinical records of JSLE patients who received at least one dose of any anti-SARS-CoV-2 vaccine were retrospectively reviewed. Data about disease activity, treatment, anti-SARS-CoV-2 vaccination and COVID-19 infection were collected. RESULTS: Sixty-five JSLE patients received at least one dose of anti-SARS-CoV-2 vaccination, while 46 patients completed the schedule with the booster. The rate of mild-moderate adverse events was 66%, mainly comprising fever, fatigue, arthromyalgias and pain at injection site. The rate of adverse events after the booster was similar to that registered after the first two doses. No significant changes after SARS-CoV-2 vaccination in BILAG and SLEDAI were observed. Disease flare rate (mainly LN) after immunization was 10.8%. Flares occurred predominantly in patients with moderate disease activity before immunization; accordingly, SLEDAI ≥4 identified patients at risk of flare while Lupus Low Disease Activity State (LLDAS) plays a protective role against post-vaccination flare. CONCLUSIONS: This study confirms that anti-SARS-CoV-2 vaccination in JSLE is well tolerated; a strict clinical monitoring and a thoughtful choice of vaccination timing should be devoted to patients not in LLDAS due to the risk of post-vaccine flare.

Juvenile Idiopathic Arthritis, Uveitis and Multiple Sclerosis: Description of Two Patients and Literature Review.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood, while multiple sclerosis (MS) is a demyelinating disease of the central nervous system, characterized by remission and exacerbation phases. An association between MS and rheumatologic diseases, in particular rheumatoid arthritis, has been described and numerous studies acknowledge anti-TNF-α drugs as MS triggers. Conversely, the association between MS and JIA has been reported merely in five cases in the literature. We describe two cases of adult patients with longstanding JIA and JIA-associated uveitis, who developed MS. The first patient was on methotrexate and adalimumab when she developed dizziness and nausea. Characteristic MRI lesions and oligoclonal bands in cerebrospinal fluid led to MS diagnosis. Adalimumab was discontinued, and she was treated with three pulses of intravenous methylprednisolone. After a few months, rituximab was started. The second patient had been treated with anti-TNF-α and then switched to abatacept. She complained of unilateral arm and facial paraesthesias; brain MRI showed characteristic lesions, and MS was diagnosed. Three pulses of intravenous methylprednisolone were administered; neurological disease remained stable, and abatacept was reintroduced. Further studies are warranted to define if there is an association between JIA and MS, if MS represents JIA comorbidity or if anti-TNF-α underpins MS development.

Pregnancy in juvenile idiopathic arthritis: maternal and foetal outcome, and impact on disease activity.

Objective: This retrospective cohort study describes the modulation of disease activity during gestation and in the year following delivery as well as maternal and neonatal outcomes in a monocentric cohort of women with juvenile idiopathic arthritis (JIA). Methods: Disease activity was assessed using DAS28-CRP before conception and every 3 months during pregnancy and in the first year postpartum. The risk of complicated pregnancies was measured applying a generalized estimating equation model. Changes in disease activity during gestation and in the first year postpartum were assessed in a linear mixed model for repeated measures. Results: Thirty-one women (49 pregnancies) with persisting JIA and at least one conception were enrolled. Adjusted DAS28-CRP levels remained stable from preconception through the first trimester, but increased significantly in the second and decreased not significantly in the third. In the postpartum, adjusted disease activity peaked at 3 months after delivery, stabilized at 6 months to decrease at 1 year, although not significantly. Preconceptional DAS28-CRP and number of biological drugs predicted disease activity fluctuation during gestation. The number of biological drugs and the length of gestational exposure to biologics significantly predicted pregnancy morbidity. In particular, JIA women had a higher probability of preterm delivery compared with healthy and disease controls. Adjusted for breastfeeding and DAS28-CRP score in the third trimester, postconceptional exposure to biologics was inversely related with disease activity in the postpartum: the longer the patient continued treatment, the lower the probability of experiencing an adverse pregnancy outcome. Conclusion: These data offer novel insights on how treatment affects disease activity during pregnancy and postpartum as well as obstetric outcomes in women with JIA.

Hyaluronic Acid Therapy in Hip OA Does Not Perform Equally in Osteoarthritis Secondary to Juvenile Idiopathic Arthritis When Compared to Primary Osteoarthritis: A 2-Year Preliminary Evaluation.

OBJECTIVE: Hip involvement in juvenile idiopathic arthritis (JIA) is one of most important causes of pain and disability. Total hip arthroplasty (THA) is considered the standard when medical approaches fail to relieve pain. However, THA is problematic for many reasons. As current literature lacks studies valuating medical management of osteoarthritis (OA) secondary to JIA, we assessed the long-term pain relief effect of US-guided intra-articular viscosupplementation in hip osteoarthritis secondary to JIA versus primary OA under different etiological conditions. METHODS: Patients in both groups received intra-articular Hylan G-F 20 2 ml once a month for 3 consecutive months and every 6 months for 2 years as maintenance. Effectiveness (VAS and WOMAC), NSAID/analgesic consumption, tolerability, withdrawals and reason for discontinuation were collected at each time point. An inverse probability weighting was used to balance the two groups. RESULTS: We retrospectively retrieved data of 14 JIA patients and 26 primary OA. Weighting successfully accounted for differences between the disease groups supporting the results. Viscosupplementation led to an early and significant improvement of pain and function and concomitant decrease in NSAIDs consumption, while the response diverged over 1 year with loss of benefits in JIA. The worst outcome was observed in active JIA. CONCLUSIONS: Duration of symptom relief after intra-articular injection of hyaluronic acid depends on the nature of arthritis. Multiple courses of viscosupplementation are required to maintain low-dose NSAIDs consumption in patients responsive to treatment while shortening the time between consecutive injections might provide persistent positive results in patients suffering from JIA.

Long Term Experience in Patients With JIA-Associated Uveitis in a Large Referral Center.

Objectives: To describe demographic, clinical and therapeutic findings of a large cohort of patients with JIA-associated uveitis in a nationwide referral pediatric rheumatology and uveitis center in Northern Italy. Methods: Retrospective study of 125 patients with JIA-associated uveitis followed from 2009 to 2019. Demographic and rheumatologic features including JIA ILAR classification, age at onset, and laboratory data were recorded. Ocular findings collected were: anatomic location of uveitis, laterality, type, recurrence rate, visual acuity, ocular complications, and local therapy. Systemic therapy with conventional and biologic immunosuppressants, occurrence of adverse events, and duration of treatments were recorded. Results: One hundred and twenty-five patients with JIA-associated uveitis were followed for a meantime of 9.2 (±1.7) years. Oligoarticular JIA was present in 92.8% of patients and anterior uveitis in 96%. The most common ocular complications recorded in our sample were posterior synechiae (37.6%), cataract (20.8%), band keratopathy (19.2%), glaucoma (7.2%), and macular edema (5.6%). Conventional immunosuppressants were used in 75.2% of patients with a mean duration of 9.1 years (±5.4), while biologics were administered in 47.2% of them for a period of 5.4 years. Adverse events (AE) were seen in 23% of patients being treated with Methotrexate, in 10.4% of patients treated with Adalimumab, in 38.5% of patients in therapy with Infliximab, and in 14.3% of patients being treated with Tocilizumab. No AE were reported in patients treated with Golimumab, Certolizumab, Abatacept and Rituximab. Conclusions: An aggressive treatment approach for patients with JIA-associated uveitis ensured a low number of ocular complications with a good safety profile.

Early Joint Replacement in Juvenile Idiopathic Arthritis: Trend Over Time and Factors Influencing Implant Survival.

OBJECTIVE: To describe early prosthesis implantations in a cohort of patients with juvenile idiopathic arthritis (JIA) followed in a tertiary referral hospital and to analyze possible factors influencing implant survival. METHODS: This was a retrospective cohort study. Charts of all patients with JIA who underwent total joint replacement at Gaetano Pini Hospital, Milan, Italy from January 1992 to June 2019 were retrieved, and relevant data were analyzed. RESULTS: Eighty-five patients met the inclusion criteria for this study, with a median follow-up period of 17.2 years. The median age at first prosthesis was 22.7 years. The total number of replaced joints was 198 over a period of 27 years. The hip was the most frequently replaced joint, accounting for almost two-thirds of the total number of implants; the other one-third refers mostly to knee implants. Polyarticular JIA and systemic JIA were the most represented JIA categories in the study cohort. A significant upward trend of the age at arthroplasty and of disease duration before arthroplasty over decades was found. The rates of implant survival at 5, 10, and 15 years were comparable (from 84% to 89%); 50% of implants lasted ≥20 years. CONCLUSION: We reported retrospective data on early joint replacement in a cohort of patients with JIA. We observed a progressive and significant upward trend of both age at arthroplasty and disease duration before the first arthroplasty over time. The JIA category, year of implant, and presence of complications significantly affected implant survivorship.

Hyaluronic Acid Injections in the Treatment of Osteoarthritis Secondary to Primary Inflammatory Rheumatic Diseases: A Systematic Review and Qualitative Synthesis.

The purpose of this study is to review the current literature on the use of hyaluronic acid (HA) specifically applied to the treatment of osteoarthritis (OA) secondary to primary inflammatory rheumatic diseases. Osteoarthritis should be carefully considered because it has potentially devastating effects on health-related quality of life. Locally injected HA seems to be an effective treatment for OA but it is not clear how to place this treatment in the context of inflammatory rheumatic disorders. To retrieve relevant articles, we conducted the search through MEDLINE, EMBASE and Cochrane Databases performing the PICO strategy. We finally selected four randomized clinical trials and six observational studies and grouped them in accordance with its main objective within three focuses: the clinical effect of HA therapy in joints without any signs of inflammation, the clinical effects of HA therapy in joints with active synovitis, and the involvement and changes of synovial fluid in the treatment of secondary OA. Our qualitative analysis clearly showed that the current literature is marked by high levels of heterogeneity and therefore difficult to interpret. Therefore, our hypothesis that viscosupplementation should be considered as a treatment for chronic moderate symptomatic OA secondary to inflammatory rheumatic diseases, and not for flares with joint swelling, cannot be definitely supported. Well-designed studies are necessary to definitively clarify the range of application of intra-articular HA injections in the treatment of inflammatory rheumatic disorders.

Comparison of Early vs. Delayed Anakinra Treatment in Patients With Adult Onset Still's Disease and Effect on Clinical and Laboratory Outcomes.

Background: Aim of this study was to search for any difference in the outcome of patients with adult onset Still's disease (AOSD) treated with anakinra (ANK) in relation with the interval between disease onset and the start of anti-interleukin(IL)-1 treatment and according with the different lines of ANK treatment. Patients and Methods: One hundred and forty-one AOSD patients treated with ANK have been retrospectively assessed. Statistically significant differences (p < 0.05) were analyzed in the frequency of ANK effectiveness, primary or secondary inefficacy to ANK and rate of resolution of clinical and laboratory AOSD manifestations after 3, 6, and 12 months since ANK treatment according with different lines of treatment and different times between AOSD onset and start of ANK. Results: No significant differences were identified in the ANK effectiveness and frequency of primary or secondary inefficacy for patients starting ANK within 6 months (p = 0.19, p = 0.14, and p = 0.81, respectively) or 12 months (p = 0.37, p = 0.23, and p = 0.81, respectively) since AOSD onset compared with patients starting ANK thereafter; no significant differences were identified in ANK effectiveness and primary or secondary inefficacy according with different lines of ANK treatment (p = 0.06, p = 0.19, and p = 0.13, respectively). Patients starting ANK within 6 and 12 months since AOSD onset showed a significantly quicker decrease of erythrocyte sedimentation rate and C-reactive protein than observed among patients undergoing ANK treatment after 6 and 12 months. The number of swollen joints at the 3 month follow-up visit was significantly lower among patients undergoing ANK within 6 months since AOSD onset (p = 0.01), while no significance was identified at the 6 and 12 month assessments (p = 0.23 and p = 0.45, respectively). At the 3 and 6 month visits, the number of swollen joints was significantly higher among patients previously treated with conventional and biological disease modifying anti-rheumatic drugs (DMARDs) compared with those formerly treated only with conventional DMARDs (p < 0.017). Conclusions: Clinical and therapeutic outcomes are substantially independent of how early ANK treatment is started in AOSD patients. However, a faster ANK effectiveness in controlling systemic inflammation and resolving articular manifestations may be observed in patients benefiting from IL-1 inhibition as soon as after disease onset.

Correction to: Proposal for a definition for response to treatment, inactive disease and damage for JIA associated uveitis based on the validation of a uveitis related JIA outcome measures from the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC).

Following publication of the original article [1], we have been notified that the author Joan Calzada should not have been included to the team of authors. The authors' team, thus, should be as follows.

JAK inhibitors in refractory juvenile idiopathic arthritis-associated uveitis.

To present our preliminary experience with JAK inhibitors in treating patients affected by juvenile idiopathic arthritis (JIA) and associated uveitis. Case series. Four consecutive patients with long-term history of juvenile idiopathic arthritis and severe associated uveitis were included in the study. Indication for treatment with JAK inhibitors was uncontrolled arthritis and/or uveitis despite different treatments with conventional and biologic disease modifying antirheumatic drugs (DMARDs). While on treatment with JAK inhibitors, namely, baricitinib (three cases) and tofacitinib (one case), all our patients showed improvement of uveitis defined as a reduction of intraocular inflammation according to Standardized Uveitis Nomenclature criteria. However, we observed a different response to treatment between the uveitis and the articular disease, as the latter did not respond as favorably as the former. Overall, the treatment was well tolerated by all patients and no ocular discomfort, ocular side effects, or allergic reactions were registered. JAK inhibitors may provide a new valuable treatment option in the therapeutic armamentarium for patients affected with JIA-associated uveitis, particularly in those refractory cases that are not adequately responding to conventional or biologic DMARDs.Key Points• A subset of patients with JIA uveitis either remain unresponsive or experience loss of efficacy• JAK inhibitors may provide a new valuable treatment option in JIA patients with uveitis• The safety profile was good with no occurrence of systemic side effects.

Proposal for a definition for response to treatment, inactive disease and damage for JIA associated uveitis based on the validation of a uveitis related JIA outcome measures from the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC).

BACKGROUND: JIA-associated uveitis (JIAU) is a serious, sight-threatening disease with significant long-term complications and risk of blindness, even with improved contemporary treatments. The MIWGUC was set up in order to propose specific JIAU activity and response items and to validate their applicability for clinical outcome studies. METHODS: The group consists of 8 paediatric rheumatologists and 7 ophthalmologists. A consensus meeting took place on November 2015 in Barcelona (Spain) with the objective of validating the previously proposed measures. The validation process was based on the results of a prospective open, international, multi-centre, cohort study designed to validate the outcome measures proposed by the initial MIWGUC group meeting in 2012. The meeting used the same Delphi and nominal group technique as previously described in the first paper from the MIWGUC group (Arthritis Care Res 64:1365-72, 2012). Patients were included with a diagnosis of JIA, aged less than 18 years, and with active uveitis or an uveitis flare which required treatment with a disease-modifying anti-rheumatic drug. The proposed outcome measures for uveitis were collected by an ophthalmologist and for arthritis by a paediatric rheumatologist. Patient reported outcome measures were also measured. RESULTS: A total of 82 patients were enrolled into the validation cohort. Fifty four percent (n = 44) had persistent oligoarthritis followed by rheumatoid factor negative polyarthritis (n = 15, 18%). The mean uveitis disease duration was 3.3 years (SD 3.0). Bilateral eye involvement was reported in 65 (79.3%) patients. The main findings are that the most significant changes, from baseline to 6 months, are found in the AC activity measures of cells and flare. These measures correlate with the presence of pre-existing structural complications and this has implications for the reporting of trials using a single measure as a primary outcome. We also found that visual analogue scales of disease activity showed significant change when reported by the ophthalmologist, rheumatologist and families. The measures formed three relatively distinct groups. The first group of measures comprised uveitis activity, ocular damage and the ophthalmologists' VAS. The second comprised patient reported outcomes including disruption to school attendance. The third group consisted of the rheumatologists' VAS and the joint score. CONCLUSIONS: We propose distinctive and clinically significant measures of disease activity, severity and damage for JIAU. This effort is the initial step for developing a comprehensive outcome measures for JIAU, which incorporates the perspectives of rheumatologists, ophthalmologists, patients and families.

Transitional care of young people with juvenile idiopathic arthritis in Italy: results of a Delphi consensus survey.

OBJECTIVES: To present the results of a Delphi consensus survey among Italian paediatric and adult rheumatologists on transitional care (TC) of young people (YP) with juvenile idiopathic arthritis (JIA). METHODS: A taskforce of 27 paediatric and adult rheumatologists evaluated the applicability of the 2016 EULAR/PReS recommendations for TC to the Italian rheumatology practice and healthcare system and formulated additional country-specific statements aimed to increase their suitability. After a two-round discussion, applicability of EULAR/PReS recommendations and agreement with newly-proposed statements were voted on a 0-10 scale (where 0 = no applicability/agreement and 10 = total applicability/agreement). A mean level of agreement ≥8 was deemed acceptable. RESULTS: The consensus threshold was reached for only 4 of the 12 EULAR/PReS recommendations and for 25 of the 27 country-specific statements. Poor agreement with EULAR/PReS recommendations was mostly explained by paucity of centres in Italy that possess both paediatric and adult rheumatologists, disagreement about optimal time of transition start and de nition of transition coordinator, diversity between paediatric and adult clinimetric assessments, and lack of administrative and financial support. CONCLUSIONS: This consensus initiative represents an important step forward toward the establishment of a nationwide TC network for YP with JIA in Italy. The main goals established for the future are the identification of adult rheumatology centres that are willing to participate in the TC process, the education of adult rheumatology teams on childhood-onset rheumatic diseases and transition issues, and the increased awareness of public healthcare authorities and other stakeholders about the importance of good-quality TC.

Long-Term Retention Rate of Anakinra in Adult Onset Still's Disease and Predictive Factors for Treatment Response.

Background: Anakinra (ANA) is an effective treatment choice in patients with adult onset Still's disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the decision to discontinue treatment after long-term clinical remission. Objectives: Aims of this study were: (i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); (ii) to identify predictive factors of lack of efficacy, loss of efficacy, and ANA withdrawal owing to long-term remission. Methods: AOSD patients classified according with Yamaguchi criteria and treated with ANA were retrospectively enrolled in 18 Italian tertiary Centers. Demographic, laboratory, clinical and therapeutic data related to the start of ANA (baseline), the 3-month assessment and the last follow-up visit while on ANA treatment were retrospectively collected and statistically analyzed. Results: One hundred and forty-one AOSD patients (48 males, 93 females) treated with ANA for a mean period of 35.96 ± 36.05 months were enrolled. The overall DRR of ANA was 44.6 and 30.5% at the 60- and 120-month assessments, respectively, with no significant differences between: (i) biologic naïve patients and those previously treated with other biologics (log-rank p = 0.97); (ii) monotherapy and concomitant use of cDMARDs (log-rank p = 0.45); (iii) systemic and chronic articular types of AOSD (log-rank p = 0.67). No variables collected at baseline could predict primary inefficacy, while the number of swollen joints at baseline was significantly associated with secondary inefficacy (p = 0.01, OR = 1.194, C.I. 1.043-1.367). The typical AOSD skin rash was negatively related with ANA withdrawal owing to long-term remission (p = 0.03, OR = 0.224, C.I. 0.058-0.863). Conclusion: Long-term DRR of ANA has been found excellent and is not affected by different lines of biologic treatment, concomitant use of cDMARDs, or type of AOSD. The risk of losing ANA efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of ANA withdrawal related to sustained remission.

Patients with juvenile idiopathic arthritis become adults: the role of transitional care.

Most juvenile idiopathic arthritis (JIA) patients need to attend adult rheumatology centres to continue the clinical management of their disease and to receive adequate long-term treatment. Transition from the paediatric to the adult health care team is a critical moment in the clinical history of these patients, but unfortunately, about 50% of the transfer processes to adult rheumatology are not successful, putting these patients at high risk of unfavourable outcomes. There are several obstacles to the success of transitional care for JIA patients, such as the absence of specific criteria for the assessment of disease activity, the lack of specific treatment recommendations for JIA adult patients, the poor adolescent-specific training for adult rheumatologists, and the shortage of resources. The improvement in the transition process in medical care has become a priority in many health care systems, but not many studies evaluating transition models, and common methodologies for measuring transition outcomes are available. The aim of this review is to identify and describe the models of transitional care in JIA, providing insights and recommendations to develop effective transitional care models in this disease.

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis.

OBJECTIVE: Anti-TNF-α agents have significantly changed the management of juvenile idiopathic arthritis (JIA). We evaluated the safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-associated uveitis in patients treated for ≥ 2 years. METHODS: Patients with JIA-associated uveitis treated with IFX and ADA were managed by a standardized protocol and data were entered in the ORCHIDEA registry. At baseline, all patients were refractory to standard immunosuppressive treatment or were corticosteroid-dependent. Data recorded every 3 months were uveitis course, number/type of ocular flares and complications, drug-related adverse events (AE), and treatment switch or withdrawal. Data of patients treated for ≥ 2 years were analyzed by descriptive statistics. RESULTS: Up to December 2014, 154 patients with ≥ 24 months followup were included in the study. Fifty-nine patients were treated with IFX and 95 with ADA. Clinical remission, defined as the absence of flares for > 6 months on treatment, was achieved in 69 patients (44.8%), with a better remission rate for ADA (60.0%) as compared to IFX (20.3%; p < 0.001). A significant reduction of flares was observed in all patients without difference between the 2 treatment modalities. The number of new ocular complications decreased in both groups but was lower for ADA (p = 0.015). No serious AE were recorded; 16.4% of patients experienced 35 minor AE and the incidence rate was lower with ADA than with IFX. CONCLUSION: At the 2-year followup, ADA showed a better efficacy and safety profile than IFX for the treatment of refractory JIA-associated uveitis.

Baseline ultrasound examination as possible predictor of relapse in patients affected by juvenile idiopathic arthritis (JIA).

OBJECTIVES: To define the correlation between joint ultrasonography and clinical examination in patients with juvenile idiopathic arthritis (JIA) and to assess whether synovitis detected by ultrasonography in clinically inactive patients predicts arthritis flares. METHODS: 88 consecutive patients with JIA-46 (52%) with persistent oligoarthritis, 15 (17%) with extended oligoarthritis, 15 (17%) with rheumatoid factor-negative polyarthritis and 12 (14%) with other forms of JIA, all clinically inactive for a minimum of 3 months-underwent ultrasound (US) assessment of 44 joints. Joints were scanned at study entry for synovial hyperplasia, joint effusion and power Doppler (PD) signal. Patients were followed clinically for 4 years. RESULTS: US was abnormal in 20/88 (22.7%) patients and in 38/3872 (0.98%) joints. Extended oligoarthritis and rheumatoid factor-negative polyarthritis were more frequent in US-positive than in US-negative patients (35.0% vs 11.8% and 30.0% vs 13.2%, respectively; P=0.005). During 4 years of follow-up, 41/88 (46.6%) patients displayed a flare; 26/68 (38.2%) were US-negative and 15/20 (75%) were US-positive at baseline. Abnormality on US examination, after correction for therapy modification, significantly increased the risk of flare (OR=3.8, 95% CI 1.2 to 11.5). The combination of grey scale and PD abnormalities displayed a much higher predictive value of relapse (65%, 13/20) than grey scale alone (33%, 6/18). CONCLUSIONS: US abnormalities are a strong predictor of relapse at individual patient level. Irrespective of treatment, the risk of flare in US-positive versus US-negative patients was almost four times higher. In case of US abnormalities, patients should be carefully followed regardless of both the International League of Associations for Rheumatology and Wallace categories.

Flares After Withdrawal of Biologic Therapies in Juvenile Idiopathic Arthritis: Clinical and Laboratory Correlates of Remission Duration.

OBJECTIVE: To assess the time in remission after discontinuing biologic therapy in patients with juvenile idiopathic arthritis (JIA). METHODS: We enrolled 135 patients followed in 3 tertiary-care centers. The primary outcome was to assess, once remission was achieved, the time in remission up to the first flare after discontinuing treatment. Mann-Whitney U test, Wilcoxon's signed rank test for paired samples, chi-square tests, and Fisher's exact test were used to compare data. Pearson's and Spearman's correlation tests were used to determine correlation coefficients for different variables. To identify predictors of outcome, Cox regression model and Kaplan-Meier curves were constructed, each one at the mean of entered covariates. RESULTS: The majority of enrolled patients flared after stopping treatment with biologics (102 of 135, 75.6%) after a median followup time in remission off therapy of 6 months (range 3-109 months). A higher probability of maintaining remission after discontinuing treatment was present in systemic-onset disease compared to the rest of the JIA patients (Mantel-Cox χ2 = 8.31, P < 0.004). In analysis limited to children with JIA with polyarticular and oligoarticular disease, patients who received biologics >2 years after achieving remission had a higher probability of maintaining such remission off therapy (mean ± SD 18.64 ± 3.3 months versus 11.51 ± 2.7 months [P < 0.009]; Mantel-Cox χ2 = 9.06, P < 0.002). No other clinical variable was significantly associated with a long-lasting remission. CONCLUSION: Children with oligoarticular and polyarticular JIA who stop treatment before 2 years from remission have a higher chance of relapsing after biologic withdrawal.

Real-life 10-year retention rate of first-line anti-TNF drugs for inflammatory arthritides in adult- and juvenile-onset populations: similarities and differences.

The aim of this study is to retrospectively analyze 10-year drug survival of first-line TNF inhibitor (TNFi) in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA) patients, comparing withdrawal rates and discontinuation pattern between adult- and juvenile-onset populations. RA, AS, PsA, and JIA patients treated with infliximab, etanercept, or adalimumab as first TNFi between 1999 and 2015 were extracted from a local registry. Drug survival up to 10-year follow-up was evaluated by the Kaplan-Meier method and compared according to age (adult vs juvenile onset), TNFi agent, and discontinuation reason by a stratified log-rank test. Three hundred sixty JIA (205 etanercept, 66 adalimumab, and 89 infliximab) and 951 (607 RA, 188 AS, and 156 PsA) adult patients (464 infliximab, 262 adalimumab, and 225 etanercept) were included. After exclusion of systemic-onset JIA (18.5%), overall 10-year retention rate was 31.8%, with no difference between adult- and juvenile-onset patients (32.1 and 30.2%, respectively; HR 0.938 [95% CI 0.782-1.125]). Etanercept showed the highest drug survival in adult-onset population (p < 0.0001 vs both monoclonal antibodies) and infliximab the lowest in juvenile-onset population (p = 0.005 vs adalimumab and p < 0.0001 vs etanercept). Inefficacy was the most frequent reason for TNFi withdrawal in adult population (29.75%) with a significantly higher risk of discontinuation than in juvenile-onset subgroup (HR 1.390 [95% CI 1.060-1.824]). Serious infections and malignancies caused TNFi withdrawal only in adult whereas gastrointestinal, neuropsychiatric, and ocular complications quite only in juvenile patients. Despite a similar 10-year drug survival, adult- and juvenile-onset subpopulations showed a significantly different pattern of TNFi reasons for discontinuation.