ABSTRACT
Background/Aims Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to >=1 biologic disease modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study. We aimed to evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECTPsA 2. Methods Pts were randomized to UPA 15mg (UPA15), UPA 30mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatmentemergent adverse events (TEAEs) were summarized for pts who received >=1 dose of study drug using visit-based cut-off at wk 104. Results A total of 641 pts received >=1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks. Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 were consistent with that reported at wk 56. Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and two with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion In PsA pts with prior inadequate response or intolerance to>=1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to two years of treatment. No new safety signals were identified in this long-term extension.
ABSTRACT
Background: The Covid pandemic and subsequent lockdown had implications on the population's mental health, particularly amongst society's most vulnerable members. We looked at the impact of the Covid pandemic on both generalised anxiety and health anxiety in women living with HIV (WLHIV). This research aimed to examine any increases in anxiety, what caused these increases, and how WLHIV dealt with them. Method(s): 12 WLHIV, aged 31-62 years old, completed recognised anxiety questionnaires (General Anxiety Disorder (GAD-7) and Health Assessment Questionnaire (HAQ)) to ascertain levels of anxiety and health anxiety respectively. Participants also responded to two open-ended questions: what made you most anxious during Covid lockdown and how did you deal with it? Results: Pre-covid GAD-7 scores averaged 6.3 indicating mild anxiety throughout the sample compared to postcovid scores of 12.9, which indicated moderate anxiety. Average HAQ scores were 21.3 indicating moderate health anxiety throughout the sample. Lack of self-advocacy skills (in relation to health) and isolation were commonly reported as being causes of anxiety;additional reasons included preexisting health issues and inability to access medical appointments and support. Participants reported using exercise, watching TV, sleep and prayer as coping mechanisms. Conclusion(s): The results of this research demonstrated that the Covid pandemic played a major part in raising anxiety, health anxiety and health worries in our sample. This was largely caused by increased isolation and decreased self-advocacy skills. Participants used individualised tools to manage their anxiety. Isolation: Isolation increased women's anxiety and health anxiety as they had no one to talk issues through with and social and organisational support was reduced due to lockdown. Lack of self-advocacy: Many participants reported that during the lockdown they found it difficult to identify and communicate their health concerns, advocate for themselves medically and subsequently negotiate help and support. Recommendations include future programmes to assist WLHIV to improve their self-advocacy skills and increase their attendance at groups/be actively involved with peers to reduce isolation. Supporting and improving advocacy helps women to gain more knowledge about their rights in relation to health care and empowers them to seek answers and negotiate treatment for themselves.
ABSTRACT
Purpose: Gout in kidney transplant (KT) recipients can be severe and particularly challenging to manage. Pegloticase co-therapy with immunomodulators improved urate lowering therapy (ULT) response rates over phase 3 monotherapy trials by reducing anti-drug antibodies.1,2 This open-label trial (PROTECT NCT04087720) examined pegloticase safety and efficacy in KT patients with uncontrolled gout. Method(s): KT recipients with uncontrolled gout (serum urate [SU]>=7 mg/dL, intolerance/ inefficacy to ULT and >=1 of the following: tophi, chronic gouty arthritis, >=2 flares in past year) and functioning KT graft (eGFR>=15 ml/min/l.73m2) on stable immunosuppressive (IS) therapy (KT>l year earlier) received pegloticase (8 mg every 2 weeks for 24 weeks). SU response during Month 6 (SU <6 mg/dL for >=80% of time) and Health Assessment Questionnaire (HAQ) pain (most severe: 100) and Disability Index (HAQ-DI, max: 3) scores were evaluated. Patients discontinuing treatment before Month 6 were considered nonresponders. Patients discontinuing due to COVID-19 concerns were excluded from analysis if no data points were available in Month 6. Result(s): 20 patients enrolled (mean+/-SD;age: 53.9+/-10.9 years, 85% male, time since KT: 14.7+/-6.9 years, SU: 9.4+/-1.5 mg/dL, gout duration: 7.9+/-11.6 years;all on >=2 IS) and 14/20 completed treatment. 16/18 (88.9% [95% CI: 65.3, 98.6]) were SU responders vs 43.5% previously reported3 without immunomodulation. Substantial SU reductions during treatments were reported in 18/20 patients completing or discontinuing for non-SU monitoring rule reasons (pre-dose SU>6 mg/dL at 2 consecutive visits). No notable eGFR changes were observed up to 3 months follow-up. In patients completing treatment, HAQ-pain and HAQ-DI mean scores improved by 35.5+/-31.5 and 0.3+/-0.6, respectively, at Week 24 (n=13 and n=14). 7 serious adverse events, deemed unrelated to pegloticase, were reported in 5 patients. No anaphylaxis or infusion reaction events occurred. Conclusion(s): Pegloticase was safe and effective in treated KT patients with uncontrolled gout, achieving a higher durable response rate than in previously-reported patients not on IS therapy along with improved HAQ scores indicative of quality of life impact. These findings are consistent with other reports of immunomodulation with pegloticase.
ABSTRACT
Background: The COVID-19 pandemic accelerated the use telemedicine for rheumatologic patients. Patient reported outcomes (PRO) can provide prioritization criteria for the form of face-to-face care in situations of social restriction, and optimization of early care by identifying high-risk patients. Objectives: Our aim was to demonstrate the main associated factors for a fall or fracture reported by rheumatoid arthritis (RA) patients in an electronic MDHAQ (Multidimensional Health Assessment Questionnaire) during this period. Methods: Patients with RA according to 2010 ACR/EULAR and access to digital platforms were enrolled in the study, from January to august 2021. A weblink was sent to MDHAQ in electronic platform. The study was approved by the ethics committee of Hospital de Clínicas de Porto Alegre-Brazil and all patients agreed with a Term of Informed Consent. Results: A total of 129 RA patients completed the electronic MDHAQ, mean age was 60 years (S.D. 14) and 83% were female. The mean DAS28, SDAI and HAQ were 3.8 (S.D. 1.6), 14.2 (S.D. 11.0) and 1. 2 (S.D. 0.7). Of those 129 patients, 14 reported a fall or fracture in the last 6 months of response and only 16 patients were physically active. Relevant symptoms known as factors associated with risk of fall and its prevalence in this study were: pain (82%), followed by articular pain (68%), fatigue (43%), muscle weakness (37%) and weight gain (22%). Among patients who reported a fall or fracture, 83% had a RADAI ≥ 16 and mean FAST3 (Fibromyalgia Assessment Screening Test) index of 19 (IC95 % 17-21). FAST3 based on MDHAQ and independent RADAI showed positively association with a reported fall or fracture for these patients, with a p value of 0.023 and 0.025, respectively. Other factors, such as high disease activity based on DAS28 or MDHAQ, obesity and age were not statistically signifcant with the reported episode. Conclusion: Maintaining PRO is aligned with patient-centered care, allowing relevant data source and identifcation of high-risk patients-in our study: patients in pain, sedentary and in major risk of fracture. Also, use of combined in like FAST3 or independent articular pain scores such as RADAI, might be helpful to identify those high-risk patients in need for orientation for reinforcement of physical activity, prioritization for in person visits and early clinical adjustments.
ABSTRACT
Background: According to 2019 updated EULAR recommendations, therapy of Early Rheumatoid Arthritis (ERA) with biological disease-modifying antirheu-matic drugs(bDMARDs) is adviced in presence of poor prognostic factors,I.e. persistently moderate/high disease activity, high acute phase reactants, high swollen joint count, autoantibody positivity, presence of early erosions, failure of two/more conventional synthetic DMARD. Objectives: To evaluate over time prevalence of bDMARD therapy and factors associated to rapid initiation in our EA Clinic (EAC), comparing two different periods: from 2004 to 2012 and from 2012 to 2020. The last two years were not considered because of the adverse influence of COVID19 pandemia on early access to EAC and on timely scheduled visits. Methods: A total of 281 ERA patients with less than 12 months of disease duration (53.9 years mean age, 75% female, 77% seropositive), followed according to the treat-to-target (T2T) strategy, were enrolled in the study. At baseline, and every three months, the ACR/EULAR core data set variables were recorded. At baseline and every year, hand and foot radiographs were examined according to modifed Total Sharp score (mTSS). At each visit, clinical improvement and remission were evaluated according to EULAR criteria. The achievement of Comprehensive Disease Control (CDC) (28-joint Disease Activity Score using C reactive protein <2.6, Health Assessment Questionnaire <0.5 and change from baseline in mTSS ≤0.5) was assessed every year. Results: We examined 164 patients from 2004 to 2012 and 117 subjects from 2012 to 2020. In the frst group 72 patients (43.9%) initiated bDMARDs during the 8-year FU, with a mean delay of 41.8 months. In the second group 37 patients (31.6%) started biotechnological drugs over time, with a mean delay of 50.4 months. Analyzing the period from 2004 to 2012, ERA patients starting bDMARDs were younger (p<0.0001), had longer disease duration (p=0.02) and higher body mass index (BMI) (p=0.01) compared to subjects not undergoing to biological therapy. Moreover, ERA patients in bDMARDs were in higher percentage anti-citrullinated peptide antibody (ACPA) positive (80.6%) and reached to a lesser extent CDC at 12months of FU (26.1%) compared to patients that didn't initiate bDMARDs (60.9% ACPA positive, p=0.01;63% achieving CDC, p<0.0001, respectively). Examining the period from 2012 to 2020, bDMARD-treated ERA patients were younger (p=0.06),in higher percentage ACPA positive (81.1%) and erosive at baseline (35.1%) compared to patients that didn't initiate bDMARDs (64% ACPA positive, p=0.02;17.5% erosive, p=0.04, respectively). As previously, patients in bDMARD reached to a lesser extent CDC at 12 month of FU (35.1%) compared to subjects not undergoing to biological therapy (55% achieving CDC, p=0.05). On multivariate analysis, ACPA positivity was associated with initiation of bDMARD in both patient groups (p=0.02), whereas older age at onset and reaching CDC at 12 month were inversely associated (p=0.001;p<0.0001, respectively). Conclusion: Despite the widest choice of bDMARDs currently available in the last 8 years, we did not observe an increase in the prescription of these drugs from 2012 to 2020. As in other ERA cohorts, bDMARD initiation is associated to poor prognostic factors, in particular ACPA positivity, presence of erosions at baseline and not achieving CDC at 12 months of FU. In the last 8 years, the decreased influence of disease duration at onset and of BMI could be a consequence of the improvement in strategies of early referral and control of modifable risk factors.
ABSTRACT
Background: Multimodal rheumatologic complex treatment (MRCT) is a treatment concept for patients with rheumatologic diseases requiring acute inpatient care suffering from exacerbated pain and/or functional impairment. A rheumatol-ogist directs the treatment program including multimodal assessments and treatment from three of the following: ergotherapy, physiotherapy, pain medicine and cognitive behavioural treatment. Most studies evaluated data from a two-week inpatient MRCT program.1 Available data on the effectiveness of a one-week inpatient multimodal treatment program are scarce. However, whether a shorter program might also be effective has not been studied so far. Objectives: To evaluate the effectiveness of a one-week inpatient multimodal and interprofessional treatment program on musculoskeletal pain and function of patients with rheumatologic disorders. Methods: 59 consecutive patients were entered into a program of multimodal treatment courses (MRCT) from January 2021 until December 2021. All patients completed a total of 11 hours of therapy in one week. Two patients were excluded for evaluation (one patient acquired COVID 19 during hospitalization and one patient was excluded due to missing data). Pain was assessed via visual analogue scale (VAS) and functional impairment via the 'Funktionsfragebogen Hanover (FFbH)' and the 'Health Assessment Questionnaire (HAQ)' at admission, at discharge and at 12 weeks of follow up. Paired t-test analyses for all treatment episodes were performed. Results: The mean treatment duration (days, ±SD) was 8.1 ± 0.8. Mean age (years, ±SD) of the 57 patients treated in the MRCT program was 57.2 ± 12.5, with 72% female and 28% male patients. Of all patients, 40% had an underlying infammatory disorder, 60% a non-infammatory rheumatic disease. 23% of all patients had 'back pain', 14% 'spondyloarthritis' and 11 % 'rheumatoid arthritis'. Overall, VAS (pain) mean at admission was 6.9 ± 1.0 (SD), HAQ mean 0.57 ± 0.23 (SD) and FFbH mean 81.44 ± 7.95 (SD), respectively. Signifcant improvements in VAS, HAQ and FFbH were demonstrated at discharge (day 8), with a mean improvement of VAS of-2.86 (95% CI:-3.07 to-2.64, P value: <0.0001), a mean improvement of HAQ of-0.24 (95% CI:-0.28 to-0.20, P value: <0.0001) and a mean improvement of FFbH of 5.38 (95% CI: 3.78 to 6.98, P value: <0.0001). Follow up assessment at week 12 was recorded in 22 patients (39%) with a signifcant mean improvement in VAS of-2.23 (95% CI:-2.98 to-1.48), P value < 0.0001) (Table 1 and Figure 1). Conclusion: Signifcant improvement of pain and function was demonstrated at discharge and at week 12 in patients with rheumatologic diseases and mus-culoskeletal pain completing a one-week inpatient multimodal interprofessional treatment program. A multimodal therapeutic approach may provide an effective treatment strategy superior to unimodal standard management.
ABSTRACT
Background: During the COVID-19 pandemic, the patients with rheumatic disease in the biopsychosocial perspective have been adversely affected by social isolation, uncertainty, and the thought that their chronic disease will worsen and increase in their symptoms. ACR/EULAR (American College of Rheumatology/European League Against Rheumatism) defnes recommendations about continuing current pharmacotherapy and the signifcance of the biopsychosocial approach and exercise for patients with rheumatic diseases during a COVID-19 infection 1, 2. Objectives: This study aims to investigate the effectiveness of the biopsychoso-cial exercise performed by telerehabilitation on biopsychosocial status, general health status, and anxiety-depression levels in the patients with infammatory and non-infammatory rheumatic diseases. Methods: Fourteen patients with infammatory rheumatic diseases (rheumatoid arthritis: 4;ankylosing spondylitis: 4;sjogren's syndrome: 3;polymyalgia rheumatica: 2;and vasculitis: 1) and eight patients with non-infammatory rheumatic diseases (fbromyalgia: 6;and osteoarthritis: 2) performed a biopsychoso-cial-based exercise model (named as 'Bilişsel Egzersiz Terapi Yaklaşimi'-(BETY) in original;'Cognitive Exercise Therapy Approach' in English) via telerehabilita-tion continued for three sessions per week for 12 months 3. Outcome measures were Health Assessment Questionnaire (HAQ), Hospital Anxiety and Depression Scale (HADS), and BETY-Biopsychosocial Questionnaire (BETY-BQ) 4. All outcomes were measured baseline and at the 12th month. The Wilcoxon's test was used for statistical analysis. Results: All of the 22 patients were female. The mean age was 57.4 and 55.8 years in the infammatory and non-infammatory rheumatic diseases groups respectively, and they had a mean BMI of 25.9 and 25.3 kg/m2. There was no signifcant difference by time for HAQ score (p = 0.125), HADS anxiety and depression (p = 0.916 and p = 0.663, respectively), and BETY-BQ score (p = 0.753) between the baseline and at the 12th month follow-up in the patients with infammatory rheumatic diseases. Similarly, in the patients with non-in-fammatory rheumatic diseases, there was no signifcant difference by time for HAQ score (p = 0.546), HADS anxiety and depression (p = 0.343 and p = 0.527, respectively), and BETY-BQ score (p = 0.068) between the baseline and at the 12th month follow-up. Conclusion: This study showed that biopsychosocial-based exercise through real-time telerehabilitation was able to maintain their conditions before pandemic in biopsychosocial status, general health, and anxiety-depression levels on the patients with infammatory and non-infammatory rheumatic diseases during COVID-19 pandemic period in one-year follow-up.
ABSTRACT
Background: Over 5 million deaths from the COVID-19 disease have been reported in the world. Patients (pts) living with rheumatoid arthritis (RA) affecting the immune system or under immunosuppressive agent are considered as a high risk population for a SARS-CoV-2 infection. Since no antiviral treatment is available, the vaccination is a major option. Objectives: The aim of this study is to evaluate in our RA cohort a questionnaire about the COVID-19 vaccination willingness, to analyse the vaccination rate, the number of COVID infection, the RA fares and the side effects. Methods: We included pts with RA from the UCLouvain Brussels cohort who met the ACR/EULAR 2010 classifcation criteria. A simple and standard questionnaire about the vaccine willingness was distributed in 2020 before the vaccination. From January to December 21, the rate of vaccination was calculated. The number of Covid infections, RA fares, therapy switches and side effects were also collected. All patient and RA characteristics were analyzed. Results: 605 eligible RA pts were included. The average age of the population is 58.21 years. 72% of the patients are women. 21% are smokers and 65% are positive for anti-citrullinated protein antibody (ACPA) with a mean DAS28-CRP of 2.39 and a mean HAQ of 0.821. In 2020, 460 pts flled the questionnaire and 61% indicated they would receive the vaccine as soon as it is available. For the 179 pts (39%) who decline, the reasons for not having vaccine were no trust in the vaccine at this time (53%), fear of side effects (28%), opposition to vaccine (4%), previous SARS-CoV-2 infection (2%) and unknown (5%). Pts under the age of 50, women, low education grade, smokers, presence of RF/ACPA and treatment with a bioDMARD were less willing to receive the vaccine. In 2021, 538 pts were vaccinated and only 67 pts (11.1%) not. The majority received a mRNA vaccine (81.8%). 72 and 21 pts developed a SARS-CoV-2 infection before and after the vaccination, respectively. Among them, 5 were admitted to intensive care unit leading to 4 deaths. Only, 7 RA fares were observed and 17 pts switched the therapy. 101 adverse events were reported. All of them were mild and transient except 2 cases with pulmonary embolism and one case with Herpes Zooster infection. Conclusion: The SARS-COV-2 global pandemic is responsible of many medical dramas. In our RA cohort, we observed frst hesitation followed by a high rate of vaccination. The safety was reassuring with a minimal number of RA fares and serious adverse events including only 4 deaths.
ABSTRACT
Background: Given the progressive change in the management of infammatory diseases,an observational study was conducted on the management of Early Rheumatoid Arthritis (ERA) in Catalonia. Objectives: To know the management of ERA in Catalonia, to assess whether the recommendations of the EULAR/ACR guidelines are followed and to study the causes of management variability,to set improvement objectives. Methods: An observational,descriptive,and cross-sectional study was conduct-ed,with data collection from June 15 to 30, 2021.The rheumatologists' partners of the Catalan Society of Rheumatology were the object of study. An online survey was conducted with 304 members on the management of the ERA. Variables related to the characteristics of the respondents,the derivation and variables of the disease including clinical variables,type of treatment and outcomes used for follow-up including the impact of the SARS-CoV2 pandemic were included. The univariate study was performed using a study of proportions with Pearson's correlation. Results: A total of 105 members (34.5%) responded to the survey.11.6%>60 y, only 7.8% <30y. 99% were in public assistance.The number of rheuma-tologists per service is 7.2[1-17],but 34.2% had< 5 rheumatologists,with a reference population of 200,000-300,000p in 42% of respondents.The number of weekly visits made is 67.5[20-130].42.2% do not have a monographic RA or ERA dispensary and 30.4%not have specialized nursing.Characteristics of ERA:77.5% are derived from primary care(PC),52% have been between 6 weeks,42.1%>3 months.54.9% make a frst visit within 2-4 weeks of PC referral and 14.7%> 8 weeks.100%provide previous analysis,only 47% had had RX performed.98% were previously treated(50.4%NSAIDs + CG,36.1%NSAIDs,12.3% CG).4.3% had GC doses>10 mg/day,11.3%> to 20mg/day.The treatment:DMARDs of choice in 100% is MTX,44.1% start doses of 10mg/week and 3.9%7.5 mg/week.The route of choice is oral(55.9% vs 44.1%).92.2% associate GC and 31.7% have not withdrawn them after 6 m.57.8% consider the maximum of MTX 25mg/W.87.1% use doses<10 mg/day,with the most used dose being 5 mg/day(35.6%).Follow-up after the start of DMARDs is performed 72.5% between 4-6 weeks and 12.7% is performed by nursing.100% use DAS 28 and 53.5% also CDAI.31.4% perform PROs(HAQ 83.3%,RAPID 3 14.3%).The use of systematic ultrasound is collected in 33%, being himself who performs it in 59.9% and an expert rheu-matologist in 46.1%.Finally, when asked about incidence of pandemic in the follow-up,53.3% consider that it is doing the same as before. 46.1% consider that telephone visits are not suitable for the follow-up of the ERAvs14.7% who consider that Yes.When questioning the situations in which they consider them to be appropriate,75.9% that it was adequate in the control after the beginning of the DMARDs.Regarding the treatment of ERA, 66% delayed the onset of biological DMARDs, 72.1% due to difficulty of follow-up and only 8.8% due to an increased risk of infection. When performing the univariate analysis, it is evident that having a monographic dispensary is associated with earlier onset of MTX(p< 0.001)and at doses≥15 mg/W(p = 0.05),greater nursing intervention(p< 0.001),greater use of PROs(p = 0.008)and there is a tendency to a shorter waiting time for frst visits(p = 0.07).It is also associated with not considering telephone visits(p< 0.001), making them in less than 25%(p< 0.0001).Similarly,hospital level is directly proportional to initiation at higher doses of MTX(p< 0.0001),lower use of GC<10mg.Among the rest of the variables, no association has been found. Conclusion: The recommendations of EULAR/ACR in the treatment and follow-up of ERA are consistently followed,although the wide use of MTX orally is striking.It is evident that the variable that most influences the early onset of FAME and at higher doses,is a monographic dispensary,as well as greater presence of nursing and performance of PROs.
ABSTRACT
Background: There has been a major concern about the impact of COVID-19 in patients with infammatory arthritis during the pandemic, with recommendations from governments for patients to shield. Objectives: Our aim was to describe the risk factors for COVID-19 hospitalisation and mortality amongst patients recruited to the National Early Infammatory Arthritis Audit (NEIAA) in England. Methods: An observational cohort study design was used. The population included adults in England with new diagnoses of infammatory arthritis between May 2018 and March 2021 who enrolled in NEIAA. The outcomes were hospitalisation due to COVID-19 (primary admission reason or nosocomial acquisition) and death due to COVID-19 (COVID-19 stated on a death certifcate), identifed via linkage with secondary care records. Hazard ratios were calculated using Cox proportional hazards models, with adjustment for patient factors (age, gender, smoking status, and comorbidity) and disease factors (seropositivity, 28-joint disease activity score, patient-reported disability (HAQ), and functional impact (MSK-HQ)) recorded at baseline. Individuals were considered at risk from the date of diagnosis or February 2020 (whichever was later) and censored at a COVID-19 event, death or May 2021 (whichever was sooner). Results: 14,127 patients were included. The mean age was 57 years;62% were female;19% were current smokers, while 29% were ex-smokers. The frequency of comorbidities at baseline were: hypertension (19%), diabetes mellitus (9%), and lung disease (9%). Overall, 20% had two or more comorbidities. Rheumatoid factor or CCP antibodies were positive in 56%. At presentation, mean scores for DAS28 were 4.6 (+/-1.5), 1. 1 (+/-0.7) for HAQ, and 25 (+/-11) for MSK-HQ. Initial DMARD therapy was known for 13,682/14,127 patients: methotrexate was the most common (54%), followed by hydroxychloroquine (23%), and sulfasalazine (11%). There were 143 COVID-19 hospital admissions and 47 deaths, corresponding to incidence rates per 100 person-years for hospitalisation: 0.94 [95% CI: 0.79-1.10] and death: 0.31 [95% CI: 0.23-0.41]. Increasing age, male gender, diabetes, hypertension, lung disease and smoking status all predicted COVID-19 hospitalisation and death. Higher baseline DAS28 predicted COVID-19 hospitalisation (HR 1.24 [95% CI: 1.10-1.39]) and mortality (HR 1.33 [95% CI: 1.09-1.63]). Higher HAQ predicted both COVID-19 hospitalisation and death. Seropositivity was not a signifcant predictor of any COVID-19 event, nor was MSK-HQ. In unadjusted models, corticosteroids associated with COVID-19 death (HR 2.29 [95% CI: 1.02-5.13], and sulfasalazine monotherapy associated with COVID-19 hospitalisation (HR 1.93 [95% CI: 1.04-3.56]. In adjusted models, associations for corticoster-oids and sulfasalazine were no longer signifcant. Only age, smoking status, and comorbidities independently predicted COVID-19 events. Conclusion: The burden of COVID-19 amongst early arthritis patients was substantial during the pandemic, with concerns about the use of csDMARDs and corticosteroids.1,2 Patient characteristics and rheumatoid disease severity at diagnosis appear to be the more important predictors of COVID-19 events than initial treatment strategy. An important limitation is that we have not looked at treatment changes over time, and must acknowledge that many patients, especially those recruited in 2019, may have changed therapy prior to the pandemic.
ABSTRACT
Background: One of the problems with the COVID-19 epidemic is infodemic. Insufficient and inaccurate information can be confusing and hinder treatment. In Japan, tabloid TV show might be an easily accessible source of information, but its reliability is low and it has a harmful effect on patients' mental status and lifestyle. There are no reports to examine what is the source of COVID-19 news for patients with rheumatoid arthritis and how these information affect patients' daily lives and disease activity. By using NinJa, Japanese largest database of rheumatoid arthritis, it may be possible to examine them in detail. Objectives: To investigate the impact of the COVID-19 news sources on rheumatoid arthritis patients' lifestyle and their disease activity using NinJa 2020 cohort study. Methods: At the timing of collection of patients' data of NinJa2020, questionnaire about their lifestyle and news source of COVID-19 was given. Questionnaire includes questions about frequency of scheduled visit, going out and exercise, weakness and news source. Results: 6677 patients out of 15553 patients answered questionnaire. Most patients did not change the interval of scheduled visit. The frequency of hospital visits was 'unchanged' in 85.8%, 'longer' in 13.6%, and 'shortened' in 0.6%. The chances of going out were 'unchanged' at 14.4%, 'signifcantly decreased' at 57.5%, 'slightly decreased' at 27.8%, and 'increased' at 0.3%. 42.6% answered that the amount of exercise did not change, 30.2% answered that it decreased considerably, 26.1% answered that it decreased a little, and 1.1% answered that it increased. Regarding muscular strength and physical strength, 46.0% answered 'no change', 19.9% answered 'signifcantly dropped', 33.5% answered 'slightly dropped', and 0.6% answered 'increased'. The media used as information sources are 'newspaper (86.4%)', 'tabloid show (54.5%)', 'family, acquaintances and friends (43.7%)', and 'official web of Ministry of Health, Labor and Welfare and academic societies (9.4. %)'. Respondents often referred to multiple media and 30.6% of them listed three sources (Figure 1). There was a positive correlation between the decrease in frequency of going out and the number of information sources, and a negative correlation between age and the number of information sources. We also found a negative correlation with age for muscle weakness. No correlation was found between the number of information sources and SDAI, CDAI, HAQ-DI, EQ-5D, HADS (A), HADS (D). Conclusion: The more sources of information, the less chance of going out. About 80% of the patients refrained from going out, the opportunity for exercise decreased in more than 50% of the patients, and the decrease in physical ft-ness was also noticed in nearly 50% of the patients. Newspapers, tabloid shows, and acquaintances were the most common sources of medical information, and relatively few patients used official sources. He provision of accurate information about COVID-19 was important to avoid infodemic. From this questionnaire, more practical information delivery system was required in Japan.
ABSTRACT
Background: Infiximab is usually given every 8 weeks. To increase dosage, the dose can be increased or the interval between infusions shortened. To minimize patient visits and workload for the medical staff during the Corona pandemic, we intended to change all infiximab infusions to 8 week intervals. For patients with infammatory bowel disease, a trough level of serum (s-) concentration of infixi-mab of 3-7 μ g/ml is recommended. In Rheumatology the usefulness of assessing s-concentration is controversial. (1, 2) Objectives: To evaluate if 8 week interval infiximab dosage, with retained weekly dose, can be used in arthritis patients, without worsening of disease activity or general health and study if s-concentration of infiximab is related to disease activity and general health. Methods: All arthritis patients on stable infiximab treatment were evaluated at the time for infiximab infusion. Disease activity, DAS28-CRP, VAS pain, global, fatigue, doctors' global, HAQ, and ASDAS-CRP, BASFI for spondyloarthritis (SpA) patients were registered in the Swedish Rheumatology Quality registry (SRQ). Blood tests for CRP, ESR and s-concentration of infiximab were taken before infusion start. S-concentration was analysed at Karolinska Hospital, Solna, Sweden with an in-house ELISA. Antibodies were assessed if s-concentration was <0.5 μ g/ml. Patients with infusion intervals less than 8 weeks were recommended a switch to 8 week intervals with maintained weekly dose of infiximab. The new dose was given the same day and patients with changed doses were re-evaluated after 24 weeks. Paired samples T-test and Wilcoxon signed rank test for paired data were used for comparison of disease activity and general health after dosage change. Linear regression analyses were used to explore associations between s-concentration, disease activity and general health. Results: Of 91 assessed patients, 66 with shorter intervals were recommended dosage change. The remaining 25 patients had infiximab every 8 weeks and served as controls. For baseline characteristics see Table 1. Dosage was changed in 58 patients and 90% (n=52) remained on 8 week intervals after 24 weeks, with a mean (SD) dose of infiximab of 5.3 (1.9) mg/kg. All assessed disease variables (DAS28-CRP, VAS pain, global, fatigue, Dr global, HAQ, ASDAS-CRP, BASFI, CRP and ESR) remained unchanged (p=0.051 (pain)-0.83) (Figure 1 A, B) while S-concentration was lower (p<0.001) at follow up. S-concentration of infiximab did not relate to disease activity neither at baseline nor at follow up (p=0.15-0.24). (Figure 1 C, D) Conclusion: Adjustment of infiximab dosage to every 8 weeks worked for a majority of the arthritis patients in this clinical setting without worsening of disease activity or general health. S-concentration of infiximab did not relate to disease activity or general health.
ABSTRACT
Background: The need to avoid the transmission of COVID19 infection has forced to promote teleconsultations for rheumatic diseases follow-up. However, remote monitoring for rheumatic diseases which require clinical examination, as rheumatoid arthritis (RA), may affect to the evaluation of clinical activity, including the biological therapies follow-up. Due to that, count on tools as Patient Reported Outcomes (PROs) could help the remote monitoring of patients when it is not advisable their physical presence in health centers, being a great help in RA control. Objectives: We aim to assess the association among the tiredness, disability and pain perception with the clinical activity in RA patients. Methods: We performed a prospective observational study of three months of follow-up in RA patients (ACR/EULAR 2010) who are newly on biological or anti-JAK therapy. A basal visit and 1, 3 months follow-up visits were conducted. We analyzed changes during follow-up in the PROs parameters reported by patients through FACIT-fatigue and HAQ questionnaires, as well as pain VAS (0-10). Moreover we measured clinical activity through Das28, Das28-CRP, SDAI and CDAI index. Results: We included 60 patients (83.3% female), with a mean age of 55 (13) and mean disease evolution of 13 (11) years. At the basal visit, 55% of them exhibited increased levels of CRP and the 48.3% of ESR, showing moderate or high clinical activity the 83.3% of the total patients. 39 patients started anti-JAK therapy and 21 with TNF-α inhibitors. The 33.34% of patients were under monotherapy, and the 46.67% previously have been treated with biological therapy. The 77.36% of the total number of patients was on the biological therapy at 6 months of follow-up, while the 22.64% discontinued at 6 months of follow-up (9 due to inefficacy and 3 due to adverse effects). 48 patients continued the treatment in the 6 months after, and 12 patients discontinued due to ineffectiveness or drug intolerance. Clinical activity, fatigue, disability and pain perception are shown in Table 1. Using a mixed linear regression model the association among the fatigue, disability and pain perception with clinical activity was conducted, corrected by age, smoking habits, time of disease evolution, BMI, previous biological/anti-JAK therapy administration and current dose of steroids. We observed a signifcant association among clinical activity and fatigue (P<0.001), disability (P<0.001) and pain perception (P<0.001). The statistical analyses showed a signifcant association where a high fatigue is increased in cases with high pain perception (P>0.001) and high number of swollen joints (P=0.002), but not in high levels of CRP and ESR. Fatigue was higher in those cases whom discontinued treatment (P=0.044) regardless of which therapy was chosen. No effect of age, time of disease evolution, steroid dose, BMI or previous therapy and smoking habits in the PROs values was observed. Conclusion: PROs would be helpful in the disease control in those cases where a remote monitoring is needed, since HAQ or FACIT-FATIGUE index showed a signif-cant association with clinical activity index in RA. Because of its ease for shipping and handling by the health professional, PROs could be a useful tool in the disease control. Its implementation in the remote monitoring of RA patient, as has been the case of Covid19 pandemic, results in an improvement of the clinic evaluation of RA patient, due to required information to clinical management is reported, avoiding presence consultation in those situations when it is required.
ABSTRACT
Background: Vaccine hesitancy is defned by the OMS as 'a delay in acceptance or refusal of vaccines despite availability of vaccination services' [1], and it is considered as one of threats to global health. This hesitancy emerges around Covid-19 vaccination. Patients on biologic Disease-Modifying Anti-Rheumatic Drug (bDMARD) are vulnerable to Covid-19 infection and their perception to vaccination is unknown. Objectives: The aim of our study was to identify Covid-19 vaccine hesitancy among rheumatoid arthritis (RA) patient on bDMARD. Methods: We conducted a monocentric, cross-sectional study, including patients with RA who met the ACR/EULAR 2010 criteria. All patients were on bDMARD with or without conventional synthetic (Cs) DMARD for at least 3 months. Disease activity was assessed using the Disease Activity Score (DAS) 28 (CRP) and the functional impairment using the Health Assessment Questionnaire (HAQ). A structured interview was done using a prepared questionnaire evaluating their vaccine hesitancy behavior. Results: We enrolled 60 patients: 10 male (16.7%) and 50 females (83.3%). Their average age was 58.16±9.04 years [34-80]. For the education level;38.5% of patients were illiterate, 34.6% had primary education, 23.1% had secondary education, and 3.8% have a university degree. Forty-four patients (73.3%) had no occupation, 13 patients (21.7%) were employed, and 5% were retired. The majority of patients lived in urban areas (85%) and 98.2% with their families. The average duration of RA was 15.23±8.92 years [2-39]. The average DAS28 (CRP) and the average HAQ were 4.05±1.22 [1.5-7.2] and 0.7±0.4 [0-2.4], respectively. Fifteen patients (25%) had a high disease activity and seven (11.7%) were in remission. When asking patients about their Covid19 infection and vaccination status;15% had caught the virus and 61.7% have already received the vaccine. One third (35.6%) believed that they had enough information about vaccination. Their main sources were their family, friends, and the media. More than half of the asked patients (68.3%) reported vaccine hesitancy. Reasons of vaccine hesitancy were divided into three categories: lack of confdence (66.7%, p<0.005) (63.3% fear related to side effects, 10% conspiracy theory, 6.7% lack of confdence in the provider), complacency problem (16.7%, p=0.01) and lack of convenience (8.6%). There was no association between vaccine hesitancy and sociodemographic data. The existence of comorbidities had no influence on vaccine hesitancy (p=0.4). This hesitancy was not associated with DAS28 (CRP) (p=0.6) and with HAQ (p=0.7). Patients with moderate to high disease activity were more likely to deny the usefulness of Covid-19 vaccination (p=0.09). Regarding to the therapeutic data, there was no association between corticotherapy and vaccine hesitancy (p=0.1). There was no influence on the type of the current bDMARD (p=0.3) or of the rate of administration (p=0.4). The route of administration was associated with hesitation (53.65% intravenous vs 46.34% subcutaneous, p=0.04). Conclusion: Our study showed that Covid-19 vaccination coverage among RA patients on bDMARDs was not optimal with a high percentage of hesitancy. The reasons are complex and they may be related to a lack of awareness. Rheuma-tologists should play a key role in the vaccine company.
ABSTRACT
Background: Patients with infammatory rheumatic diseases (IRD) have used self-isolation and social distancing during the pandemic to avoid SARS-CoV-19 infection (reference). In countries with unlimited and free access to SARS-CoV-19 testing, anxiety or other patient related factors might potentially increase test-frequency. Objectives: In patients with IRD followed in the nationwide DANBIO registry we aimed to explore clinical factors including self-isolation associated with a) a positive SARS-CoV-19 test result ('infection'), b) higher frequency of SARS-CoV-19 testing during the frst 1/ year of the pandemic. Methods: In May-June 2020, IRD patients followed in the quality registry, DANBIO (n=36,152), were invited to participate in the voluntary online questionnaire survey 'You and your rheumatic disease during times with corona-virus'. Patient characteristics, treatment and patient reported outcomes were captured in DANBIO and from the questionnaire. Patients were considered as self-isolating if they agreed to the question: I stay at home and avoid others as much as possible. After written consent, information on dates and SARS-CoV-19 test results (by PCR, polymerase chain reaction) during follow-up (until Nov 2021 and thus before entry of the Omicron variant) was obtained through linkage to the nationwide laboratory system. Time to frst positive PCR and associated characteristics were explored by multivariable Cox regression analyses with hazard ratios, HR, adjusted for: gender/age-group/diagnosis/biologic therapy/working/self-isolation/HAQ/EQ-5D. Day 0 was defned as the date of frst positive test in cohort (May-07-2020). Number of SARS-CoV-19 tests (median (IQR)), and characteristics associated with higher test frequency (upper quartile) was explored with multivariable logistic regression analyses (odds ratios, OR, adjustment like above). Results: In 10,098 included patients, 2.8% were infected during follow-up (Table 1). Age and HAQ seemed lower in infected (Table 1, Figure 1). In multivariable Cox regression analyses, male gender was associated with higher infection risk (HR 1.38 (1.05;1.80) whereas risk was lower in the age-group 61-80 years (0.60 (0.39;0.92) vs. below 40 years). Other factors were statistically insignifcant. Median number of PCR tests was 4 (IQR 1-9). In patients with <9 tests, 2.6% were infected whereas for patients with ≥9 tests, 3.2% were infected. Patients with ≥9 tests were younger, more frequently female and working in univariate (Table 1) and adjusted analyses, whereas other characteristics were statistically insignifcant (details not shown). Conclusion: Few patients with IRD were infected during the frst 1/ years of the pandemic. Gender and age were associated with infection risk and frequency of testing. Self-isolation and a range of other clinical characteristics had no impact, which to some extent may be due to behavioral differences across age-groups.
ABSTRACT
Background: Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to ≥1 biologic disease-modifying antirheu-matic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study.1 Objectives: To evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECT-PsA 2. Methods: Pts were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized for pts who received ≥1 dose of study drug using visit-based cut-off at wk 104. Results: A total of 641 pts received ≥1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks1 (Table 1). Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 (Figure 1) were consistent with that reported at wk 56.1 Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and 2 with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion: In PsA pts with prior inadequate response or intolerance to ≥1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to 2 years of treatment. No new safety signals were identifed in this long-term extension.
ABSTRACT
Background: The COVID-19 pandemic has impacted on face to face assessments of patients with rheumatic diseases, including rheumatoid arthritis (RA) and telemedicine has offered a valid opportunity to follow these patients. DEDI-CARE is a Patient Support Program (PSP) which has been active at our center since 2016, which allows the telemonitoring of PROs (Patient Reported Outcomes) for patients being treated with abatacept. Since 2016, 98 RA patients followed at out Unit entered the DEDICARE program. During COVID19 pandemic these patients continued their monitoring using this PSP. Objectives: To evaluate the impact of the frst COVID wave on PROs and CROs (Clinical Reported Outcomes) in patients with RA included in the DEDICARE programme Methods: Data collected in the dedicated platform three months before (from December 2019 to February 2020, pre-lockdown), during (from March 2020 to May 2020, lockdown) and after (from June 2020 to August 2020, post-lockdown) the frst lockdown period in Italy were compared. In detail DAS28 (CRP, ESR), CDAI and SDAI were evaluated before and after the lockdown period;while VAS-pain, Global Health (GH);Patient Global Assessment of Disease Activity (PGA);Health Assessment Questionnaire (HAQ);Functional Assessment Chronic Illness Therapy (FACIT) were evaluated pre, during e post lockdown with the DEDICARE platform. Results: 36 RA patients, all females, were included in the study;mean age was 62.4 (32-85) years;mean disease duration 15.5 (5-38) years;18 were ACPA and RF+. All patients were treated with abatacept, 13 as monotherapy and 23 in association with csDMARDs. No patients had COVID19 disease during the evaluated period. A signifcant worsening of global health and patient global assessment of disease activity was observed;while no differences were observed regarding the CROs and other PROs (Figure 1) Conclusion: In the present study we were able to compare PROs in patients with RA before and after the frst COVID wave in Italy. While no signifcant changes in disease activity were observed, patients experienced an increased perception of disease activity and a decline in their overall health status which began during the lockdown and continued over the following 3 months. This may highlight a discordance between the patient and the physician perception of the disease, which may partly due to the psychological impact of pandemic on the general perception of health particular in patients with chronic diseases. Since this discrepancy may have consequences on disease management, and particularly on treatment adherence, there is a need to promote studies to better understand the reasons for these discrepancies and to improve the patient perception of their disease particularly in difficult situations such as COVID 19 pandemic.
ABSTRACT
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.
ABSTRACT
Background: Digital solutions for online monitoring of chronic diseases are increasingly implemented in health care, but not all patients might have access, skills, or interest in using them. Fueled by the COVID-19 pandemic and the urgent need for remote consultations, an online website to enter patient-reported outcomes (PROs) from home (DANBIO-from-home, https://danbio.dk) was implemented on May 15th 2020 for patients with infammatory rheumatic diseases (IRD) followed in the Danish nationwide DANBIO registry. Objectives: To explore the use of DANBIO-from-home during the frst 1/year after launching, with focus on a) characteristics of patients who did versus who did not access the webpage, and b) impact of patient age on time to frst entry. Methods: DANBIO-from-home allows PROs to be entered remotely by computer, tablet, or smartphone after secure log-on. All patients followed in DANBIO were informed about this option by invitations sent through eBoks, a national infrastructure for electronic communication, available to 80-90% of Danish citizens. Patients were encouraged to access DANBIO-from-home before planned rheumatology consultations, or when participating in the voluntary questionnaire survey 'You and your rheumatic disease during times with corona-virus' (on three occasions: May 2020, Nov 2020, June 2021) (ref). Follow-up ended Dec 1st 2021. Characteristics of patients who did/did not access DANBIO-from-home during follow-up are explored by multivariable logistic regression analyses adjusted by clinical factors (gender/age-group/diagnosis/disease duration/use of biologics/HAQ/PASS). Time to frst entry of PRO using DANBIO-from-home is presented as cumulative incidence curves by age group. Results: Among 33,776 patients with infammatory rheumatic diseases followed in DANBIO, 68% used DANBIO-from-home at least once during follow-up (Table 1). Patients who used the system were less frequently below 40 years or above 80 years old, more frequently biologically treated and had lower HAQ-score than patients who did not use it. In logistic regression analyses, factors associated with DANBIO-from-home access were: female gender (odds ratio, OR 1. 2 (1.1;1.3)), age group 40-60 (1.8 (1.6;2.0)) or 61-80 yrs (1.9 (1.7;2.19) and not age >80 yrs (0.6 (0.5;0.7) with age <40 as the reference), biologic treatment (1.4 (1.3;1.5)), higher HAQ (1.3 (0.3;1.4)), scoring PASS 'no' (1.1 (1.02;1.2)) (all p <0.001), whereas disease duration and diagnosis had no impact. Time to frst entry was longest in in patients >80 yrs followed by the <40 yrs group. For all age-groups, and most pronounced for age <40 yrs, the use increased when invitations to questionnaire surveys were sent out. (Figure 1) Conclusion: A web-based system for secure remote entry of PROs was well-received after a nationwide launch. Patient-related factors had a substantial impact on the use. Lower use in the elderly might indicate lack of technical skills or facilities, whereas low use in younger age groups, which improved over time, is likely driven by other factors. Further analyses are planned to explore if lack of use impacts treatment outcomes.
ABSTRACT
Background: A highly controversial question is whether or not corticosteroids should be prescribed for patients with early diffuse cutaneous systemic sclerosis (dcSSc). Although the painful and disabling features of early dcSSc (including tight itchy skin, contractures, fatigue) have an infammatory basis and are likely to respond to corticosteroids, corticosteroids are a risk factor for potentially life-threatening scleroderma renal crisis. Objectives: Our aim was to examine safety and efficacy of moderate dose prednisolone in patients with early dcSSc. Specific objectives were to evaluate whether moderate dose prednisolone reduced pain and disability, and improved skin score, and whether prednisolone was safe with particular reference to renal function Methods: PRedSS set out as a Phase II, multicentre, double-blind randomised controlled trial, converted to open-label because of the Covid-19 pandemic. Patients were randomised to receive either moderate dose prednisolone (approximately 0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. The co-primary endpoints were the Health Assessment Questionnaire Disability Index (HAQ-DI) and modifed Rodnan skin core (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures refecting pain, itch, anxiety and depression, fatigue and helplessness. 72 participants randomised 1:1 were planned and anticipated to yield 60 evaluable, giving over 80% power for each co-primary outcome in ANCOVA analyses [assumptions;HAQ-DI (a = 0.025, ô =-0.6, o = 0.9, p = 0.6), mRSS (a = 0.025, ô =-5.5, a = 8.2, p = 0.6)]. Mixed Models for Repeated Measures (week 6, month 3, month 6) were ftted with covariates trial arm, baseline score, anti-Scl-70 and their interactions with time point. An unstructured covariance matrix was assumed with the primary focus being the trial arm effect at 3 months. Results: The study terminated early due to the Covid-19 pandemic and consequently did not meet the recruitment target of 72 patients. Thirty-five patients (Table 1) were randomised (17 to prednisolone and 18 to placebo/control, 25 during the double-blind phase), of whom 34 completed the 3 month assessment. The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was-0.10 (97.5% CI-0.29 to 0.10), p=0.25, and in mRSS-3.90 (97.5% CI-8.83 to 1.03), p=0.070, both favouring prednisolone but not signifcantly. Patients in the prednisolone group experienced less pain, helplessness and anxiety than control patients at 3 months: mean difference in pain scores-0.49, 95%CI (-0.93 to-0.06), p=0.027, in Hospital Anxiety and Depression (HADS) anxiety scores-2.05, 95%CI (-3.73 to-0.37), p=0.018, and in helplessness scores-1.54, 95%CI (-3.01 to-0.07), p=0.040. There were no renal crises. Conclusion: PRedSS exemplifed the challenges of running a clinical trial of an investigational medicinal product potentially associated with increased infection risk during the Covid-19 pandemic. Because PRedSS was terminated prior to target recruitment, it was underpowered, and any conclusions have to be extremely cautious. Although PRedSS suggested some beneft from moderate dose predni-solone, the small sample indicates the need for a further randomised trial.