Rituximab in a Large Uk Centre during the Covid-19 Pandemic: The Effects of Employing a Reduced Dosing Regimen on Clinical Response in Rheumatoid Arthritis Patients

Background/Aims When the COVID-19 pandemic began, steps were taken to minimise risk to those vulnerable to severe outcomes. For immunosuppressed patients with rheumatoid arthritis (RA), consideration was given to reducing risk whilst mindful of compromising control of their underlying condition. At Leeds Teaching Hospitals NHS Trust, patients receiving rituximab (RTX) were considered for a reduced dose regimen. A retrospective study, using real-world data, was undertaken to assess the impact of lower doses of RTX on response to treatment. Methods The clinical records of all patients with RA who had received RTX between March 2020 and March 2021 were reviewed. Demographics and previous RTX exposure were recorded. The dose of RTX given during the specified period was noted. Response to treatment was recorded pragmatically by physicians as good, partial or none, based on patient reported VAS for disease activity and swollen and tender joint counts, given the limitations placed on face-to-face patient review due to the pandemic. The time to subsequent RTX treatment and the need for steroid treatment for flares was also studied. Results The number of patients treated with RTX was 282, of whom 89 patients received full dose (1g x 2 infusions), 192 patients received half dose (500mg x 2 infusions). The mean age was 61 years. 77% were female. 9% were RTX-naive, 80% had previously had full dose. Follow-up data were available for 185/192 of the group receiving 1g and 88/89 of the group receiving 2g. Clinical outcomes were as follows for the two groups (1g RTX vs 2g RTX): no response 10.3% vs 9.1%;partial response:34.9% vs 20% %;good response: 54.8% vs 70.9%. The mean length of response was 7.5 months in the patients receiving 1g of RTX compared to 8.6 months in the group receiving 2g of RTX. Similar number of patients required steroid for a flare after receiving Ig of RTX (23.9%) compare to those receiving 2g of RTX (25.8%). Conclusion A majority of patients receiving RTX for RA at either standard or reduced dose reported clinical response. Those receiving lower dose RTX were more likely to report a partial response whilst those receiving full dose were more likely to report a good response. Duration of response and need for steroid therapy for flare of RA between treatments did not significantly differ between groups. Further analysis of factors that may influence clinical response to lower dose RTX is ongoing, which could guide tailored therapy regimens should the need arise again.

Nail ridging in rheumatoid arthritis patients and relation to disease activity: An integrated rheumatology-dermatology multi-centre study

Aim of the work: To evaluate the frequency of nail ridging (NR) in patients with rheumatoid arthritis (RA) and to study its relation to disease activity. Patients and methods: 230 RA patients and 97 matched controls from Helwan, Ain Shams and Mansoura university hospitals were studied. Disease activity score (DAS28) was assessed. NR has been searched for in all patients. The number of affected fingers was recorded. NR was determined by a magnifying lens, seen by naked eye or seen and felt. Dermoscopic photography of the NR using Dermalite DL4 3Gen dermatoscope has been recorded. Results: The median age of patients was 49 years (42–58 years);they were 221 females and 19 males (F:M 11.1:1) with a disease duration 9 years (5–11 years). Their DAS28 was 3.6 (2.9–4.6). NR was significantly increased in RA cases vs. control;73% vs 20%;p < 0.001. In patients, NR was detected by a magnifying lens in 32.6%, seen in 27% and seen and felt in 13.5%. Joint deformities were significantly higher in those with NR. DAS28 was a significant independent predictor of NR;for every one-point increase in DAS28, there was a 153 times higher odds to exhibit NR at a sensitivity of 93.5%, specificity 80.3% and at a diagnostic accuracy of 90%. Conclusion: NR is a frequent finding in RA. An integrated rheumatological- dermatological clinical evaluation may be helpful and further studies are required to prove the importance of this sign for follow up of RA patients.

COVID-19 in rheumatoid arthritis patients receiving baricitinib: Observations from patient registry

Background/Purpose: Rheumatoid arthritis (RA) patients have higher COVID-19 risks [1,2]. Data suggest that some RA biologics, including baricitinib, may be beneficial for COVID-19 outcomes [3,4]. We used data from RA registry to evaluate impact of COVID-19 on RA activity in patients receiving baricitinib. Method(s): Current study is a single center registry of RA patients receiving baricitinib as a part of routine treatment. Study center accumulates most of RA patients who started baricitinib in Moscow (Russia) from July 2020 to data cutoff (January 2022). We analyzed medical records data for demographics, disease history, and change of disease activity indexes. Medical record data were allocated to visit 1 (baseline), closest to 4 and 8 months after baricitinib initiation (visits 2 and 3). Patients, who had no baricitinib interruptions, were divided in strata according to COVID status between visits 1 and 2. Result(s): At the time of data cutoff registry included data from 142 RA patients receiving baricitinib. Median duration of treatment was 14.5 (interquartile range [IQR] 10-29) weeks. Clinical RA indexes measures are compiled in Table 1. Of 142 patients, 52 had COVID-19 between visits 1 and 2 without baricitinib interruption. Swollen joint counts (SJCs) and tender joint counts (TJCs) were comparable across 3 visits except TJC at visit 3 (P < 0.05). Disease Activity Score-28 for Rheumatoid Arthritis with C-Reactive Protein (DAS28-CRP), Disease Activity Score-28 for Rheumatoid Arthritis with Erythrocyte Sedimentation Rate (DAS28-ESR) had comparable change regardless of COVID-19 status (P > 0.05). Simplified Disease Activity Index for Rheumatoid Arthritis (SDAI) and Clinical Disease Activity Index (CDAI) were higher in COVID-19 survivors at visit 3 (P < 0.05). (Table Presented) Conclusion(s): We conclude that, overall, COVID-19 had no significant impact on RA activity during baricitinib treatment. Further follow-up needed to find out reasons for TJC/SDAI/CDAI increase in COVID-19 survivors >=4 months after infection.

THE PATTERN of POST COVID-19 REACTIVE ARTHRITIS

Background: According to the recent medical literature, COVID-19 disease can lead to a constellation of clinical syndromes lasting well beyond the frst 30 days of infection. The most common post COVID sequalae includes pulmonary, nervous system and neurocognitive, mental, metabolic, cardiovascular, gastrointestinal and several other clinical manifestations. Regarding joint involvement and particularly reactive arthritis (ReA), literature data is limited and describes case reports or series of cases of patients diagnosed with this condition following COVID-19 disease. Objectives: To describe the pattern and the management of post-COVID reactive arthritis. Methods: We have conducted a descriptive study of consecutive adult patients who presented to rheumatology outpatient clinic for joint or peri-articular pain/swelling/stiffness and received a diagnosis of post-COVID 19 reactive arthritis, by excluding other types of rheumatological conditions. The assessed clinical variables were: visual analogue scale (VAS) pain, swollen joint count (SJC), tender joint count (TJC), duration of morning stiffness, presence of enthesitis/tendinitis and axial involvement. Biochemistry and serology was performed: rheumatoid factor, ACPA, ANA, HLA B27, antiChlamydia Trachomatis, Ureaplasma Urealyticum and Mycoplasma Hominis Ab, anti HBs and HBc Ab, and anti HCV. COVID-19 disease prior to diagnosis of ReA was confrmed by PCR test. Results: In the study were included 16 patients with confrmed post COVID-19 ReA. The mean age of the study group was 43.5±10.8 (range 21-60), the female: male ratio was 4:1 and the duration of joint symptoms was 10.4±11.8 (range 1-42) weeks. The severity of COVID-19 disease was mild in 68.7% cases, moderate in 18.7% and severe in only 6.2% of the cases. The duration between COVID-19 diagnosis and ReA varied between cases, with a mean value of 4.3±4.2 (range 1-12) weeks. In 43.7% of the cases patients had peripheral joint involvement (synovitis), in 37.5%-periarticular involvement (enthesitis), 6.25%-isolate axial involvement (sacroiliac joints), 6.25% enthesitis and axial involvement (cervical spine) and 6.25% synovitis and enthesitis. In patients with peripheral joint pattern, the distribution of pain was symmetric (71.4%). The pattern of synovitis was determined by a TJC of 6.25±5.2 (range 1-16) joints and SJC 1.6±2.4 (range 0-7) joints. Both TJC and SJC correlated positively with the duration of morning stiffness (r=0.9 and r=0.6), but did not correlate with the VAS pain scale. In most of the cases synovitis affected the hand (wrist, MCP and PIP) 62.5% and the knee, feet and ankles-50%. Two patients presented with monoarthritis, 1 with oligoarthritis and 5 with polyarthritis, in the majority of cases, involvement being symmetric (75%). Periarticular pattern was determined by enthesi-tis, affecting the elbow and shoulder (50%), costo-sternal enthesitis (25%) and trochanteritis (25%). From the entire study group, 31.2% had elevated serum infammatory markers (ESR and/or CRP). Patients responded well to NSAIDs alone in 68.7% cases, local (intra-articular or peri-articular infltrations) or and systemic corticoids (5 mg Prednisolone equivalent) were administered in 5.3% and 12.5% cases respectively, in 12.5% cases (two patients) Methotrexate was administered. Conclusion: Reactive arthritis represents a post COVID-19 sequelae. The time of onset of ReA varied between 1 and 12 weeks after COVID-19 diagnosis. The clinical pattern of the disease was expressed by joint or periarticular involvement, mainly affecting the hand, feet and knee symmetrically. Cases of axial manifestations were less common. Most of the patients responded well to NSAIDs, only in a few particular cases, low doses of corticoids and/or Methotrexate were recommended.

EVALUATION of PATIENTS with RHEUMATOID ARTHRITIS in TELECONSULTATION during the FIRST WAVE of the COVID-19 PANDEMIC

Background: The sudden emergence of SARS-CoV-2 onto the world stage has accelerated a major change in the management of patients with chronic rheumatic diseases and has catalyzed the rapid emergence of telemedicine. Objectives: Our aim was to describe which parameters were used by rheumatol-ogists to monitor patients with rheumatoid arthritis (RA) in teleconsultation during the frst wave of the pandemic and identify the most relevant for decision making. Methods: Retrospective monocentric routine care cross-sectional study including RA patients seen in teleconsultation between March and September 2020. Available parameters assessing disease status were collected in teleconsultation files. Clinician intervention was defned by treatment escalation and/or the need for a rapid face-to-face consultation or day hospitalization. Results: 143 RA patients were included (117 females, mean age of 58±16 years, mean disease duration of 14±11 years). The presence or absence of patient self-reported RA fares was mentioned in all medical files, followed by the presence and/or the number of tender joints (76%), the duration of morning stiffness (66%), the number of pain-related nocturnal awakenings (66%) and the CRP value (54%). Patient self-reported RA fares concerned 43/143 patients (30%). The presence of self-reported RA fares was associated with a more detailed evaluation of patient in teleconsultation: The presence (or number) of tender joints and swollen joints were more signifcantly reported in patients who presented a fare (39/43, 91% vs. 70/100, 70%, p=0.008 and 25/43, 58% vs. 23/100, 23%, p<0.001, respectively). Teleconsultation led to a clinician intervention in 22/143 patients (14%), representing 51% of patients with self-reported fares (22/43 patients). Therapeutic escalation was necessary in 13 patients: introduction or dose increase of cor-ticosteroids in 8 patients, introduction or dose increase of methotrexate in 4 patients and introduction of hydroxychloroquine in 1 patient. Face-to-face consultation or day hospitalization were organized for 10 patients. Active disease was confrmed during this next face-to-face visit in 9 patients, with DAS28 ranging from 3.35 to 5.62, leading to therapeutic modifcation. The 133 other patients were seen in face-to-face consultation 6±2 months after the teleconsultation. No DMARD modifcation was recorded during this next face-to-face consultation. The following variables were associated with clinician intervention during the tel-econsultation in univariate analysis: patient self-reported RA fares since the last visit (p<0.001), CRP >10 mg/mL (p=0.012) and a morning stiffness > 30 minutes (p<0.001). Multivariate analysis confrmed RA fares (Odds Ratio, OR: 15.6 95% CI 3.37-68.28) and CRP values >10 mg/L (OR: 3.32, 95% CI % 1.12-13.27) as the variables independently associated with clinician intervention. Conclusion: Our study identifed patient reported RA fares and increased CRP values as 2 red fags in teleconsultation, independently associated with therapeutic modifcation and/or the need for a rapid face-to-face consultation. These indicators may help clinician's decision making in teleconsultation.

ARE PATIENTS with RA in REMISSION in FINLAND during the COVID TIMES? RESULTS from the FINNISH QUALITY REGISTER

Background: Worries have been expressed, concerning the care of chronic diseases during the Covid times (1). Objectives: To study the current status of patients with RA in the Finnish quality register database. Methods: Patients who receive care for RA were identifed in the database. Clinical and demographic data from the last visits during 2020-21 were collected, including swollen (SJC46) and tender joint counts (TJC46), doctor assessment of disease activity (Dr global), laboratory tests for infammatory and serology markers, patient reported outcomes (PROs), and DAS28. Regression models were applied to compare measures of clinical status between the health care regions, adjusted for gender, age, ACPA status, and disease duration. Results: A total of 14163 patients (72% female, mean (SD) age 62 (14) years, median (IQR) disease duration 8.5 (2.6, 20) years, 84% ACPA positive) were identifed. For the entire population, the median (IQR) SJC46 was 0 (0, 1), TJC46 0 (0, 2), ESR 8 (5, 18), CRP 3 (1, 6), and dr global 8 (0, 19). Among PROs, median (IQR) HAQ was 0.5 (0, 1), pain 26 (10, 51), fatigue 28 (8, 54) and patient global 29 (11, 51). Between health care regions, statistically signifcant differences were found for all variables due to a large sample size. The mean (SD) DAS28 was 2.3 (0.9) for the entire group and 69 % of all patients had DAS28<2.6. The median DAS28 ranged from 2 to 2.7 among health care regions (Figure 1) (p<0.001). Majority of patients were taking csDMARDs only. Conclusion: The quality register provides comprehensive real-world data on the current status of patients with RA. A majority of patients can be considered being in remission even during the Covid times.

IMPACT OF INTERMEDIATE TREATMENT INTERRUPTION ON SECUKINUMAB EFFICACY IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS AND ANKYLOSING SPONDYLITIS: INTERIM ANALYSIS RESULTS FROM THE SERENA STUDY

Background/Aims Secukinumab has demonstrated long-lasting efficacy and a favorable safety profile in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). SERENA is an ongoing, longitudinal, observational study in>2900 patients with moderate to severe psoriasis, active PsA, and AS. We report interim data on impact of intermediate treatment interruption on secukinumab effectiveness in patients with active PsA or AS. Methods This analysis included data for 534 PsA and 470 AS patients enrolled in SERENA between Oct 2016 and Oct 2018 and followed-up for at least 2 years. Patients (≥18 years) with active PsA or AS were required to have received ≥16 weeks of secukinumab treatment before enrolment. Treatment interruption was defined as interruption of secukinumab therapy for at least 3 months between the last injection and re-initiation. Effectiveness assessments included swollen and tender joint count in PsA patients, and Patient Global Assessment (PtGA) and BASDAI score in AS patients before and during treatment interruption and post secukinumab re-initiation. Patients with assessments in≥2 of the time periods were included. Last assessment prior to intermediate treatment interruption was used as baseline. The assessment closest to 6 months after re-initiation was considered the post-secukinumab re-initiation assessment. Results A total of 31 (5.8%) PsA patients and 42 (8.9%) AS patients had an intermediate treatment interruption since initiation of secukinumab treatment. The mean (SD) duration of treatment interruption was 24.8 (16.4) and 26.4 (22.9) weeks for PsA and AS patients, respectively. The mean (SD) duration of secukinumab treatment before the treatment interruption was 86.8 (50.3) and 90.2 (46.9) weeks, and after the treatment interruption was 73.6 (44.4) and 63.2 (46.8) weeks. The most commonly reported reasons included adverse events (AEs;18 [58.1%] PsA, 19 [45.2%] AS), patient decision (3 [9.7%] PsA, 3 [7.1%] AS), and COVID-19 outbreak-related reasons (1 [3.2%] PsA, 6 [14.3%] AS patients). More than 80% of PsA patients and 76% of AS patients reinitiated secukinumab without a loading phase after the treatment interruption. The swollen and tender joint count increased in PsA patients from the last assessment prior to the treatment interruption (1.3 [1.0] and 7.2 [11.4];n=6) to the first assessment during the treatment interruption (4.0 [1.4] and 16.5 [19.1];n=2), and gradually decreased post secukinumab re-initiation (0.4 [0.5] and 2.0 [0.7];n=5). PtGA and BASDAI remained stable in AS patients from the last assessment prior to the treatment interruption to the first assessment during the treatment interruption and after secukinumab re-initiation. Conclusion Secukinumab intermediate treatment interruption occurred due to a variety of reasons in the real-world setting, mainly AEs and patient decision. Most patients re-initiated secukinumab treatment without a loading phase. No notable impact of the intermediate treatment interruption was observed on the effectiveness of secukinumab.