Delayed follow-up of medical retina patients due to COVID-19: impact on disease activity and visual acuity

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos

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POS1234 IMPACT OF THE CHANGE IN ADMINISTRATION ROUTE OF TOCILIZUMAB AND ABATACEPT, DUE TO THE COVID-19 LOCKDOWN ON DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3126 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 900.1-900

Author(s):

L. Diebold ◽

T. Wirth ◽

V. Pradel ◽

N. Balandraud ◽

E. Fockens ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Physical Activity ◽

Disease Activity ◽

Univariate Analysis ◽

Route Of Administration ◽

Anxiety And Depression ◽

Administration Route ◽

Factors Associated ◽

The Impact

Background:Among therapeutics used to treat rheumatoid arthritis (RA), Tocilizumab (TCZ) and Abatacept (ABA) are both biologic agents that can be delivered subcutaneously (SC) or intravenously (IV). During the first COVID-19 lockdown in France, all patients treated with IV TCZ or IV ABA were offered the option to switch to SC administration.Objectives:The primary aim was to assess the impact of changing the route of administration on the disease activity. The second aim was to assess whether the return to IV route at the patient’s request was associated with disease activity variation, flares, anxiety, depression and low physical activity during the lockdown.Methods:We conducted a prospective monocentric observational study. Eligibility criteria: Adult ≥ 18 years old, RA treated with IV TCZ or IV ABA with a stable dose ≥3 months, change in administration route (from IV to SC) between March 16, 2020, and April 17, 2020. The following data were collected at baseline and 6 months later (M6): demographics, RA characteristics, treatment, history of previous SC treatment, disease activity (DAS28), self-administered questionnaires on flares, RA life repercussions, physical activity, anxiety and depression (FLARE, RAID, Ricci &Gagnon, HAD).The primary outcome was the proportion of patients with a DAS28 variation>1.2 at M6. Analyses: Chi2-test for quantitative variables and Mann-Whitney test for qualitative variables. Factors associated with return to IV route identification was performed with univariate and multivariate analysis.Results:Among the 84 patients who were offered to switch their treatment route of administration, 13 refused to change their treatment. Among the 71 who switched (48 TCZ, 23 ABA), 58 had a M6 follow-up visit (13 lost of follow-up) and DAS28 was available for 49 patients at M6. Main baseline characteristics: female 81%, mean age 62.7, mean disease duration: 16.0, ACPA positive: 72.4%, mean DAS28: 2.01, previously treated with SC TCZ or ABA: 17%.At M6, the mean DAS28 variation was 0.18 ± 0.15. Ten (12.2%) patients had a DAS28 worsening>1.2 (ABA: 5/17 [29.4%] and TCZ: 5/32 [15.6%], p= 0.152) and 19 patients (32.8%) had a DAS28 worsening>0.6 (ABA: 11/17 [64.7%] and TCZ: 8/32 [25.0%], p= 0.007).At M6, 41 patients (77.4%) were back to IV route (26 TCZ, 15 ABA) at their request. The proportion of patients with a DAS28 worsening>1.2 and>0.6 in the groups return to IV versus SC maintenance were 22.5%, 42.5% versus 11.1% and 22.2% (p=0.4), respectively. The univariate analysis identified the following factors associated with the return to IV route: HAD depression score (12 vs 41, p=0.009), HAS anxiety score (12 vs 41, p=0.047) and corticosteroid use (70% vs 100%, p=0.021), in the SC maintenance vs return to IV, respectively.Conclusion:The change of administration route of TCZ and ABA during the first COVID-19 lockdown was infrequently associated with a worsening of RA disease. However, the great majority of the patients (77.4%) request to return to IV route, even without disease activity worsening. This nocebo effect was associated with higher anxiety and depression scores.Disclosure of Interests:None declared

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Ophthalmological findings in children with non-syndromic craniosynostosis: preoperatively and postoperatively up to 12 months after surgery

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2020-000677 ◽

2021 ◽

Vol 6 (1) ◽

pp. e000677

Author(s):

Evangelia Ntoula ◽

Daniel Nowinski ◽

Gerd Holmstrom ◽

Eva Larsson

Keyword(s):

Visual Acuity ◽

University Hospital ◽

Cranial Sutures ◽

Sagittal Craniosynostosis ◽

Syndromic Craniosynostosis ◽

Disc Oedema ◽

Before And After ◽

Congenital Condition ◽

Skull Deformity

AimsCraniosynostosis is a congenital condition characterised by premature fusion of one or more cranial sutures. The aim of this study was to analyse ophthalmic function before and after cranial surgery, in children with various types of non-syndromic craniosynostosis.MethodsChildren referred to Uppsala University Hospital for surgery of non-syndromic craniosynostosis were examined preoperatively. Visual acuity was measured with Preferential Looking tests or observation of fixation and following. Strabismus and eye motility were noted. Refraction was measured in cycloplegia and funduscopy was performed. Follow-up examinations were performed 6–12 months postoperatively at the children’s local hospitals.ResultsOne hundred twenty-two children with mean age 6.2 months were examined preoperatively. Refractive values were similar between the different subtypes of craniosynostosis, except for astigmatism anisometropia which was more common in unicoronal craniosynostosis. Strabismus was found in seven children, of which four had unicoronal craniosynostosis.Postoperatively, 113 children were examined, at mean age 15.9 months. The refractive values decreased, except for astigmatism and anisometropia in unicoronal craniosynostosis. Strabismus remained in unicoronal craniosynostosis. Two new cases with strabismus developed in unicoronal craniosynostosis and one in metopic, all operated with fronto-orbital techniques. No child had disc oedema or pale discs preoperatively or postoperatively.ConclusionOphthalmic dysfunctions were not frequent in children with sagittal craniosynostosis and preoperative ophthalmological evaluation may not be imperative. Children with unicoronal craniosynostosis had the highest prevalence of strabismus and anisometropia. Fronto-orbital techniques used to address skull deformity may be related to a higher prevalence of strabismus postoperatively.

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SAT0501 EARLY START OF BIOLOGICAL TREATMENT IN JUVENILE IDIOPHATIC ARTHRITIS: DOES A THERAPEUTIC WINDOW EXIST IN REAL LIFE?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4611 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1207.2-1207

Author(s):

A. García Fernández ◽

A. Briones-Figueroa ◽

L. Calvo Sanz ◽

Á. Andreu-Suárez ◽

J. Bachiller-Corral ◽

...

Keyword(s):

Disease Activity ◽

Biological Treatment ◽

Real Life ◽

Therapeutic Window ◽

Systemic Jia ◽

Active Arthritis ◽

The Impact ◽

Active Patients ◽

Active Disease

Background:Biological therapy (BT) has changed the treatment and perspectives of JIA patients but little is known about when is the best moment to start BT and the impact of this prompt iniciation.Objectives:To analyze the response to BT of Juvenile Idiophatic Arthritis (JIA) patients according to the time when the BT was started.Methods:A retrospective, descriptive study was conducted on JIA patients followed up in a referal hospital that started BT up to 24 months after diagnosis from 2000 to 2018. Disease activity was measured, at 2 years after diagnosis, according to Wallace criteria for remission (absence of: active arthritis, active uveitis, fever, rash or any other manifestation attributable to JIA, normal CRP and ESR, PGA indicating no active disease) for at least 6 months.Results:55 JIA patients that started BT up to 24 months from diagnosis were analyzed. 69,1% were girls with a median age at diagnosis of 8 years old IQR(3-13), median age at the start of BT of 9 years old IQR(3-13). Regarding JIA categories: 25,5% were Oligoarticular Persistent (OligP), 18,2% Systemic JIA (sJIA), 16,4% Entesitis related Arthritis (ERA), 12,7% Psoriatic Arthritis (APso) and Polyarticular RF- (PolyRF-), 5,5% Oligoarticular Extended (OligE) and Polyarticular RF+ (PolyRF+), 3,6% Undifferentiated (Und). 20% of patients had uveitis during followup. Conventional DMARD (cDMARD) was indicated in 83,6% of patients (95,7% Methotrexate) at diagnosis [median 0 months IQR(0-2,3)]. At the end of followup (2 years) only 30,9% of patients continued with cDMARDs. The main causes of discontinuation were: adverse events (46,7%), remission (36,7%). TNF inhibitors were precribed in 81,8% of patients and 18,2% of patients recieved two BT during the first 2 years from diagnosis. 54,5% of BT were indicated during the first 6 months from diagnosis, 27,3% from 7 to 12 months, 12,7% from 13 to 18 months, 5,5% from 19 to 24 months.After 2 years from diagnosis, 78,2% of patients were on remission and 21,8% active. Among patients with active disease: 75% had arthritis, 16,7% had uveitis and 8,3% had both. There were no differences regarding disease activity among patients with uveitis and neither taking cDMARDs. Regarding JIA categories: 66,7% of OligE, 57,1% of PolyRF- and 57,1% of APso patients were active at 2 years from diagnosis when compared to the other categories (p=0.004).Patients on remission at 24 months from diagnosis started sooner the BT than active patients [CI 95% (0,46-8,29) p=0,029]. The time when the BT was started was correlated to the activity at 2 years (K= 0,294 p=0,029). When the BT was prescribed after 7,5months from diagnosis it was correlated, in a COR curve, with a higher probability of active disease at 2 years (S= 0,67 E= 0,63). There was a correlation, among patients on remission at 2 years, between prompt start of BT and less time to reach remission (K= -0,345 p=0,024). Patients with active disease at 2 years, regardless of moment of BT iniciation, required more BT during follow-up (p=0,002).Conclusion:Prompt iniciation of BT was correlated with a better outcome. JIA patients that started BT early after diagnosis had a higher probability of remission after 2 years. Starting BT after 7,5 months was correlated with a higher probability of active disease at 2 years. Active disease at 24 months was correlated with persistent active disease during follow-up.Disclosure of Interests:None declared

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A Follow-Up Study of a European IgG4-Related Disease Cohort Treated with Rituximab

Journal of Clinical Medicine ◽

10.3390/jcm10061329 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1329

Author(s):

Johanna Backhus ◽

Christian Neumann ◽

Lukas Perkhofer ◽

Lucas A Schulte ◽

Benjamin Mayer ◽

...

Keyword(s):

Disease Activity ◽

Clinical Activity ◽

Inflammatory Disorder ◽

International Consensus ◽

Steroid Pulse ◽

Related Disease ◽

Igg4 Related Disease

Objectives: IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder affecting virtually any organ. Type 1 autoimmune (type 1 AIP) is its pancreatic manifestation. To date, steroids are considered the first-line pancreatitis treatment. The CD20-binding antibody rituximab (RTX) appears a promising steroid-sparing therapy, although long-term data are lacking. We aimed to bridge this gap with a cohort of IgG4-RD patients treated with RTX and to assess the potential value of the Responder Index (RI) as a discriminatory score for disease activity. Methods: We retrospectively evaluated 46 patients from a tertiary referral centre who were diagnosed with IgG4-RD and/or type 1 AIP according to the International Consensus Diagnostic Criteria or Unifying-AIP criteria between June 2006 and August 2019. Results: Patients resembled previous cohorts in terms of characteristics, diagnosis, and therapeutic response. Thirteen of the 46 patients with IgG4-RD/type 1 AIP were treated with RTX pulse therapy due to relapse, adverse reactions to steroids, or high-risk constellations predicting a severe course of disease with multi-organ involvement. Median follow-up after diagnosis was 52 months for all subjects, and 71 months in IgG4-RD patients treated with RTX. While patients in the RTX group showed no significant response to an initial steroid pulse, clinical activity as measured by the RI significantly decreased in the short-term after RTX induction. Within 16 months, 61% of patients relapsed in the RTX group but responded well to re-induction. Clinical and laboratory parameters improved equally in response to RTX. Conclusion: RTX therapy in patients with IgG4-RD is an effective and safe treatment to induce treatment response and possible long-term remission. Repeated RTX administration after 6–9 months may be of value in reducing the risk of relapse. The RI appears to be a reasonable index to assess disease activity and to identify patients with IgG4-related disease who may benefit from B-cell-depleting therapy.

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POS0208 GENDER DIFFERENCES IN RESPONSE TO BIOLOGICALS. WOMEN FARE WORSE ACROSS INFLAMMATORY ARTHRITIS DISEASES - DATA FROM THE BIOREG

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3596 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 320.1-321

Author(s):

E. Loibner ◽

V. Ritschl ◽

B. Leeb ◽

P. Spellitz ◽

G. Eichbauer-Sturm ◽

...

Keyword(s):

Gender Differences ◽

Psoriatic Arthritis ◽

Gender Difference ◽

Disease Activity ◽

Inflammatory Arthritis ◽

Tnf Inhibitors ◽

Significant Difference ◽

The Difference ◽

All Diseases

Background:Gender differences in prevalence and disease course are known in various rheumatic diseases; however, investigations of gender difference concerning therapeutical response have yielded variable results.Objectives:The aim of this retrospective study was to investigate, whether a gender difference in response rate to biological disease-modifying antirheumatic drugs (bDMARDs) and apremilast in bDMARD-naïve patients could be observed across the three most prevalent inflammatory arthritis diseases: rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA). Additionally, a response to individual TNF blockers was investigated in this respect.Methods:Data from bDMARD-naïve RA-, SpA- and PsA-patients from Bioreg, the Austrian registry for biological DMARDs in rheumatic diseases, were used. Patients with a baseline (Visit 1=V1) and follow-up visits at 6 months (Visit 2=V2) and 12 months (Visit 3=V3) were included and response to therapy with TNF-inhibitors (TNFi), furthermore to therapy with rituximab, tocilizumab and apremilast was analyzed according to gender. The remaining bDMARDs were not analyzed due to small numbers. Key response-parameter for RA was disease activity score (DAS28), whereas for PsoA the Stockerau Activity Score for Psoriatic Arthritis (SASPA) and for SpA the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were employed; in addition, the Health assessment Questionnaire (HAQ) was used. Data were analyzed in R Statistic stratified by gender using Kruskal-Wallis and Wilcoxon tests.Results:354 women and 123 men with RA (n=477), 81 women and 69 men with PsA (n=150), 121 women and 191 men with SpA (n=312) were included. No significant differences in biometrics was seen between female and male patients at baseline in all diseases.In RA patients overall DAS28 decreased from baseline (V1) to V2 and V3 (DAS28: V1: male: 4.38 [3.66, 5.11], female: 4.30 [3.68, 5.03], p(m/f) = 0.905; V2: male: 2.66 [1.73, 3.63], female: 3.10 [2.17, 3.98], p(m/f) = 0.015; V3: male: 2.25 [1.39, 3.36], female: 3.01 [1.87, 3.87], p(m/f) = 0.002). For TNF inhibitors (n=311), there was a significant difference between genders at V2 (Fig.1a). Patients receiving Rituximab (n=41) displayed a significantly higher DAS28 at baseline in females, which diminished in the follow up: V1: (p(m/f) p=0.002; V2: p=0.019; V3: p=0.13); response to tocilizumab (n=63) did not show any gender differences.In PsA patients overall SASPA decreased from baseline (V1) to V2 and V3 (SASPA: V1: male: 4.00 [2.80, 5.20], female: 4.40 [2.80, 5.80], p(m/f) = 0.399; V2: male: 2.20 [1.20, 3.50], female: 3.40 [2.00, 5.00], p(m/f) = 0.071; V3: male: 1.80 [0.80, 2.70], female: 3.01 [2.35, 4.80], p(m/f) = 0.001). For TNF inhibitors (n=79), there was a significant difference between genders at V3 (Fig 1a). For Apremilast (n=39), there was a significant difference between genders at V2 (Fig.1c).In SpA patients overall BASDAI decreased from baseline (V1) to V2 and V3 (BASDAI: V1: male: 4.70 [2.88, 6.18], female: 4.80 [3.30, 6.20], p(m/f) = 0.463; V2: male: 3.05 [2.00, 4.60], female: 3.64 [2.62, 5.41], p(m/f) = 0.039; V3: male: 3.02 [1.67, 4.20], female: 3.65 [2.18, 5.47], p(m/f) = 0.016). In V3 a differential BASDAI in response to TNFi (n=299) was observed (Fig.1a).Possible differences of response to individual TNFi (etanercept, infliximab, other TNFi) measured by HAQ were investigated in all diseases together. The difference between male and females was significant at baseline for all 3 TNFi; whereas with the use of ETA the significant difference was carried through to V2 and V3, it was lost with the use of IFX and was variable with the other TNFi (Fig.1b)Figure 1.Conclusion:Female patients showed a statistically lower response to TNFi in all three disease entities (RA, SpA and PsoA) to a variable degree in our homogenous central european population. Interestingly, the difference was not uniform across individual TNFi when measured by HAQ. Gender differences were also seen in response to Apremilast.Disclosure of Interests:Elisabeth Loibner: None declared, Valentin Ritschl: None declared, Burkhard Leeb Speakers bureau: AbbVie, Roche, MSD, Pfizer, Actiopharm, Boehringer-Ingelheim, Kwizda, Celgene, Sandoz, Grünenthal, Eli-Lilly, Grant/research support from: TRB, Roche, Consultancies: AbbVie, Amgen, Roche, MSD, Pfizer, Celgene, Grünenthal, Kwizda, Eli-Lilly, Novartis, Sandoz;, Peter Spellitz: None declared, Gabriela Eichbauer-Sturm: None declared, Jochen Zwerina: None declared, Manfred Herold: None declared, Miriam Stetter: None declared, Rudolf Puchner Speakers bureau: AbbVie, BMS, Janssen, Kwizda, MSD, Pfizer, Celgene, Grünenthal, Eli-Lilly, Consultant of: AbbVie, Amgen, Pfizer, Celgene, Grünenthal, Eli-Lilly, Franz Singer: None declared, Ruth Fritsch-Stork: None declared

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MTX optimization or adding bDMARD equally improve disease activity in rheumatoid arthritis: results from the prospective study STRATEGE

Rheumatology ◽

10.1093/rheumatology/keab274 ◽

2021 ◽

Author(s):

Cécile Gaujoux-Viala ◽

Christophe Hudry ◽

Elena Zinovieva ◽

Hélène Herman-Demars ◽

René-Marc Flipo

Keyword(s):

Disease Activity ◽

Biological Treatment ◽

Current Practice ◽

Treatment Strategies ◽

Route Optimization ◽

Treat To Target ◽

Inadequate Response ◽

Inclusion Criteria ◽

Treatment Optimization

Abstract Objectives The STRATEGE study aimed to describe treatment strategies in current practice in RA bDMARD-naive patients with an inadequate response to MTX therapy, and to compare clinical efficacy of the different therapeutic strategies on disease activity after six months. Methods 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/wk. 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/wk, 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.

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