Joint Morning Stiffness Research Articles

SPECIFIC BIOCHEMICAL INDICATORS AND INFLAMMATORY MARKERS IN RHEUMATOID ARTHRITIS (RA)

It is acknown that Rheumatoid inflammation is a chronic systemic autoimmune disease developing on the background of infection. Damages mainly the heart, blood vessels, musculoskeletal system and other internal organs. Multiple joints may be affected, primarily the knee, ankle and elbow undergoing destruction leads to pain, mainly symmetrical. Damaged joints swollen and skin in these foci reddens; joint morning stiffness lasts for an hour or more, this sign is accompanied by low fever and fatigue. As a result of the rheumatic process, the heart is damaged, leading to cardiovascular manifestations. Analysis of blood parameters allows the severity of the disease to be determined based on a relatively new method using Das28. The obtained results for ESR and CRP are used to calculate DAS28, which also allows monitoring of RA treatment. Most patients with rheumatoid arthritis (RA) are seropositive—they have abnormally high levels of rheumatoid factor (RF) or anti-citrullinated peptide antibodies (anti-CPP) in the blood. The article examines aspects of synthetic, chemical and alternative medicine impact on treating patients with RA as well. The article discusses comparative aspects of pharmacological and herbal medicine in the therapeutics. According to the literature, patients who have not received the expected results after treatment with pharmacological preparations successfully use herbal remedies as a means of body restoring and healing. To date, the success of traditional medicine is ahead of those of conventional using synthetic drugs.

A Real-World Effectiveness Study Using a Mobile Application to Evaluate Early Outcomes with Upadacitinib in Rheumatoid Arthritis.

The impact of upadacitinib on rheumatoid arthritis (RA) symptoms was evaluated during the first 12weeks of treatment via patient-reported outcomes (PROs) using a mobile health application (app). Participating rheumatologists from the CorEvitas RA Registry (prospective, observational cohort) recruited patients with RA initiating upadacitinib treatment. A modified version of the ArthritisPower® app was used to collect PROs, including the Routine Assessment of Patient Index Data 3 (RAPID3), duration of morning joint stiffness, and the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue 7a Short Form at baseline and weeks 1-4, 8, and 12. RAPID3 responses over time were assessed using Kaplan-Meier estimation to determine the proportion of patients achieving disease activity improvement and minimal clinically important difference (MCID). Results were analyzed for all patients initiating upadacitinib and a subsample of TNF inhibitor (TNFi)-experienced patients with moderate to severe disease at baseline. A total of 103 patients with RA initiating upadacitinib (62.1% TNFi-experienced) were included. At week 12, 53 patients (51.4%) completed the study and provided PRO data via the app. Among all patients, improvements in RAPID3, pain, morning stiffness, and fatigue were observed at week 1 and were maintained or further improved through week 12. At week 12, 37.5% of patients achieved RAPID3 low disease activity. Starting at week 1, improvements in RAPID3 disease activity category (19.4% of patients) and achievement of MCID (16.3%) were reported, with nearly 50% of patients achieving these outcomes by week 4 (RAPID3 category: 48.8%; MCID: 49.2%) and 60% by week 12 (RAPID3 category: 59.6%; MCID: 59.8%). TNFi-experienced patients generally reported similar outcomes. Patient-reported medication convenience and compliance were generally high. In this real-world cohort of patients with RA, treatment with upadacitinib was associated with early and significant improvement in RAPID3, pain, morning stiffness, and fatigue regardless of prior TNFi experience. Clinically meaningful improvement in RAPID3 patient-reported disease activity was observed as early as week 1, with continued improvement reported through week 12.

The dichotomy of glucocorticosteroid treatment in immune-inflammatory rheumatic diseases: an evidence-based perspective and insights from clinical practice.

Glucocorticosteroids (GCs) are the most used anti-inflammatory and immunosuppressive drugs due to their effectiveness in managing pain and disease modification in many immune-inflammatory rheumatic diseases (IRDs). However, their use is limited because of adverse effects (AEs). The authors analyzed recent studies, including randomized controlled trials (RCTs), observational, translational studies and systematic reviews, providing an in-depth viewpoint on the benefits and drawbacks of GC use in rheumatology. Glucocorticosteroids are essential in managing life-threatening autoimmune diseases and a cornerstone in many IRDs given their swift onset of action, necessary in flares. Several RCTs and meta-analyses have demonstrated that when administered over a long time and on a low-dose basis, GC can slow the radiographic progression in early rheumatoid arthritis (RA) patients by at least 50%, satisfying the conventional definition of a disease-modifying anti-rheumatic drug (DMARD). In the context of RA treatment, the use of modified-release prednisone formulations at night may offer the option of respecting circadian rhythms of both inflammatory response and HPA activation, thereby enabling low-dose GC administration to mitigate nocturnal inflammation and prolonged morning fatigue and joint stiffness. Long-term GC use should be individualized based on patient characteristics and minimized due to their potential AEs. Their chronic use, especially at medium/high dosages, might cause irreversible organ damage due to the burden of metabolic systemic effects and increased risk of infections. Many international guidelines recommend tapering/withdrawal of GCs in sustained remission. Treat-to-target (T2T) strategies are critical in setting targets for disease activity and reducing/discontinuing GCs once control is achieved. Glucocorticosteroids' use in treating IRDs should be judicious, focused on minimizing use, tapering and discontinuing treatment, when possible, to improve long-term safety. Glucocorticosteroids remain part of many therapeutic regimens, particularly at low doses, and elderly RA patients, especially with associated chronic comorbidities, may benefit from long-term low-dose GC treatment. A personalized GC therapy is essential for optimal long-term outcomes.

Comprehensive analysis of pain syndrome in patients with rheumatoid arthritis

Rheumatoid arthritis is a chronic systemic disease of connective tissue of immune genesis and unknown etiology. In the developed countries of the world, about 1 in 100 people suffer from rheumatoid arthritis, while in Ukraine the occurrence of the disease is 340 cases per 100,000 adult population. Chronic pain syndrome and limitation of joint functions significantly reduce the life quality of patients. At this stage, along with drug therapy, physical rehabilitation / therapy plays an important role in the restorative treatment of patients with rheumatoid arthritis. The purpose of the study is a comprehensive assessment of the main indicators of pain syndrome and morning stiffness of joints in patients with rheumatoid arthritis. 216 patients with rheumatoid arthritis were examined: 178 (82%) of them were women, 38 (18%) were men. The age of the patients is from 25 to 59 (average age is 46±0,24). The diagnosis was established on the basis of the ACR/EULAR 2010 criteria and in accordance with the Order of the Ministry of Health of Ukraine No. 263 dated November 04, 2014. A comprehensive analysis of the pain syndrome in patients with rheumatoid arthritis was carried out. Pain and severity of morning stiffness in the joints were determined using Huskisson’s visual analog scale (VAS, 100 mm). Statistical analysis was performed on the basis of the statistical analysis Statistica 10 (Serial Number: STA999K347150-W) and MEDCALC®. It was found that pain of low intensity was observed in 62 (28,7%), pain of medium intensity – in 120 (55,6%), and maximum intensity pain was experienced by 34 (15,7%) patients. It was found that in women with rheumatoid arthritis of radiological stage I, the average morning stiffness index according to VAS (100 mm) is 46,1±7,3, in men – 45,3±4,8; in women of radiological stage II, the average indicator is 52,6±7,9, in men – 50,3±6,1; in women of radiological stage III, the average indicator is 66,8±5,9, in men – 63,6±1,7. The analysis of the indicators showed that the severity of morning stiffness is more pronounced in women of all radiological stages than in men. All the above determines an urgent need to develop and implement in practice the concept of physical therapy for patients with rheumatoid arthritis in order to reduce the pain syndrome, severity of rheumatoid arthritis, eliminate morning stiffness, improve the functional condition and restore the motor functions of the joints, improve the health and quality of life of patients.

The EVALUATION OF THE USE OF ANTI-INFLAMMATORY DRUGSIN PATIENTS RHEUMATOID ARTHRITIS OUTPATIENT AT GRANDMED HOSPITAL LUBUK PAKAM

Rheumatoid arthritis is an autoimmune disease characterized by inflammation of the joints that can become chronic. Rational use of drugs aims to ensure that patients get safe and effective treatment in the right time frame and at an affordable price according to their needs In the outpatient facility of Lubuk Pakam Hospital, patients experience symptoms such as pain, inflammation, morning joint stiffness and difficulty moving at appropriate doses. This study aims to aim to obtain an objective picture or picture of the situation. Data collection was carried out retrospectively, namely by observing the medical records of rheumatoid arthritis patients at Grandmed Lubuk Pakam Hospital in 2021. A total of 13 (56.5%) female patients and 10 (56.5%) (43.5%) male patients, according to the number of rheumatoid arthritis patients at the outpatient facility of GrandMed Lubuk Pakam Hospital in 2021. This makes the inclusion criteria for all anti-inflammatory agents incomplete in rheumatoid arthritis and the exclusion criteria for all medical records in rheumatoid arthritis patients. Analysis of data based on age, gender, rationality of the drug, correct indications, correct patient, correct drug, correct dosage. The Outpatient Study of GrandMed Lubuk Pakam Hospital 2021 is: Correct Indications (100%), Correct Patients (100%), Correct Drugs (100%), Correct Dosage (91.3%). The treatment of patients with rheumatoid arthritis at GrandMed Lubuk Pakam Hospital can still be said to be fully good

Association between patient-reported outcomes and impairments in work and activity in patients with rheumatoid arthritis in clinical remission: A retrospective analysis using the IORRA database.

To explore the patient-reported outcomes (PROs) associated with work productivity and activity impairment (WPAI) in patients with rheumatoid arthritis (RA) in clinical remission. We enrolled patients with RA ≥18 years and with a simplified disease activity index ≤3.3 from the Institute of Rheumatology, Rheumatoid Arthritis data set collected in October 2017. The pain-visual analogue scale, patients' global assessment visual analogue scale (VAS), Japanese version of the Healthcare Assessment Questionnaire (J-HAQ) Disability Index, and duration of morning joint stiffness were selected as the PROs. To evaluate work productivity and activity, the WPAI for RA instrument (WPAI-RA) was used. To assess the contribution of each PRO to the WPAI-RA score, an analysis of variance model was constructed. The mean age of the 2614 patients was 62.4 years; 85.1% were female. Median values of the WPAI-RA score were 1.1% for absenteeism, 6.5% for presenteeism, 7.4% for work impairment, and 10.2% for activity impairment. Morning joint stiffness contributed the most to absenteeism (18.0%), while pain-VAS contributed the most to presenteeism (57.4%), work productivity loss (51.1%), and daily activity impairment (53.7%). J-HAQ was the second most contributing factor to presenteeism (17.4%), work productivity loss (16.3%), and daily activity impairment (26.0%). The pain-VAS and J-HAQ highly contributed to WPAI in patients with RA in clinical remission.

Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): a randomised, double-blind, placebo-controlled, proof-of-concept trial

Rheumatoid arthritis is the most common autoimmune disease worldwide and requires long-term treatment to suppress inflammation. Currently, treatment is started when arthritis is clinically apparent. We aimed to evaluate whether earlier intervention, in the preceding phase of arthralgia and subclinical joint inflammation, could prevent the development of clinical arthritis or reduce the disease burden. We conducted a randomised, double-blind, placebo-controlled, proof-of-concept-trial at the Leiden University Medical Centre, Leiden, Netherlands. Adults aged 18 years or older with arthralgia clinically suspected of progressing to rheumatoid arthritis and MRI-detected subclinical joint inflammation were eligible for enrolment across 13 rheumatology outpatient clinics in the southwest region of the Netherlands and randomly assigned (1:1) to a single intramuscular glucocorticoid injection (120 mg) and a 1-year course of oral methotrexate (up to 25 mg/week), or placebo (single injection and tablets for 1 year). Participants and investigators were masked to group assignment. Follow-up continued for 1 year after the end of the 1-year treatment period. The primary endpoint was development of clinical arthritis (fulfilling the 2010 rheumatoid arthritis classification criteria or involving two or more joints) that persisted for at least 2 weeks. Patient-reported physical functioning, symptoms, and work productivity were secondary endpoints, which were measured every 4 months. Additionally, the course of MRI-detected inflammation was studied. All participants entered the intention-to-treat analysis. This trial is registered with EudraCT, 2014-004472-35, and the Netherlands Trial Register, NTR4853-trial-NL4599. Between April 16, 2015, and Sept 11, 2019, 901 patients were assessed for eligibility and 236 were enrolled and randomly assigned to active treatment (n=119) or placebo (n=117). At 2 years, the frequency of the primary endpoint was similar between the groups (23 [19%] of 119 participants in the treatment group vs 21 [18%] of 117 in the placebo group; hazard ratio 0·81, 95% CI 0·45 to 1·48). Physical functioning improved more in the treatment group during the first 4 months and remained better than in the placebo group (mean between-group difference in Health Assessment Questionnaire disability index over 2 years: -0·09, 95% CI -0·16 to -0·03; p=0·0042). Similarly, pain (on scale 0-100, mean between-group difference: -8, 95% CI -12 to -4; p<0·0001), morning stiffness of joints (-12, -16 to -8; p<0·0001), presenteeism (-8%, -13 to -3; p=0·0007), and MRI-detected joint inflammation (-1·4 points, -2·0 to -0·9; p<0·0001) showed sustained improvement in the treatment group compared with the placebo group. The number of serious adverse events was equal in both groups; adverse events were consistent with the known safety profile for methotrexate. Methotrexate, the cornerstone treatment of rheumatoid arthritis, initiated at the pre-arthritis stage of symptoms and subclinical inflammation, did not prevent the development of clinical arthritis, but modified the disease course as shown by sustained improvement in MRI-detected inflammation, related symptoms, and impairments compared with placebo. Dutch Research Council (NWO; Dutch Arthritis Society).

Subjective symptoms contributing to the quality of life of rheumatoid arthritis patients with clinical remission from the IORRA database.

To explore patient-reported outcomes (PROs) related to quality of life (QOL) in patients with rheumatoid arthritis (RA) who achieved clinical remission. In the Institute of Rheumatology, Rheumatoid Arthritis dataset, RA patients >18 years old who met the simplified disease activity index (SDAI) remission criteria in April 2017 were enrolled in this analysis. Pain-visual analogue scale (pain-VAS) (0-100 mm), patient's global assessment of disease activity (Pt-GA; 0-100 mm), Japanese version of the Health Assessment Questionnaire, duration of morning joint stiffness, and fatigue [Checklist Individual Strength 8R (CIS)] were the tools used to evaluate PROs. To assess the contribution of each PRO to the European QOL-5 Dimensions-5 Level (EQ-5D-5L) score, an analysis of variance was conducted. Among the 2443 patients with remission, the mean EQ-5D-5L was 0.9. The mean pain-VAS and Pt-GA were 7.2 and 7.4, respectively. Factors that significantly contributed to the EQ-5D-5L were pain-VAS (48.8%), CIS score (18.1%), and Pt-GA (15.6%). Around 82.5% of the variance in EQ-5D-5L was explained by the three PROs. This study demonstrated that pain-VAS, CIS, and Pt-GA were significant contributors to the EQ-5D-5L score in patients with RA who achieved the simplified disease activity index remission criteria.

Effect of hysterectomy on the function of saved ovaries and correction of hormonal imbalance

The objective: to assess the hormonal disorders in patients after the radical treatment for leiomyoma and to develop the therapeutic options for correction.Materials and methods. The clinical and laboratory assessment of postoperative course after leiomyoma surgery in 160 women of reproductive age was carried out. The following groups of patients were formed: I group – 90 patients after vaginal hysterectomy (HE) with opportunistic salpingectomy and ovarian preservation, II group – 70 patients after abdominal HE with opportunistic salpingectomy and ovarian preservation. The control group included 50 women of reproductive age with asymptomatic leiomyoma.Then the following groups were formed to assess the effectiveness of the proposed medical correction program: the main group – 46 patients after vaginal HE with fallopian tubes and 36 persons after abdominal HE with fallopian tubes – received the proposed medical correction program, and the comparison group – 44 and 34 individuals after vaginal and abdominal HE with opportunistic salpingectomy and ovarian preservation, respectively, with standard approach for postoperative and rehabilitative periods.The diagnostic program included the assessment of hormonal level, post-hysterectomy syndrome degree by modified menopausal index using survey, urogenital and sexual dysfunction, and the indicators of vulvovaginal atrophy according to the Barlow scale.Results. Neurovegetative symptoms were observed in 36,7 % patients in the I group and 48.6 % - II group, vegetative-vascular symptoms – 46.7 % and 62.3 %, respectively. Insomnia was characterized by the sleep process disorders, the preservation of the feeling of fatigue after waking up. It is necessary to mention that an increase in the proportion of cardiovascular diseases up to 36 months after surgery (hypertension, dyshormonal cardiomyopathy and their combinations, 23.1 % were diagnosed with dyshormonal mastopathy, the women complained on arthralgia, morning joint stiffness, ostealgia twice more.The assessment of sexual disorders and manifestations of urogenital tract dysfunction allowed to indicate the most significant rate of dysuria complains in 72.9 % of cases in the II group after classical abdominal HE. Up to 36 months after surgery the subclinical hypothyroidism was found in 62.2 % of women in the I group and 31.4 % – II group, clinically significant hypothyroidism – in 21.1 % and 55.7 %, respectively.In the half of the cases the hormonal imbalance like hypoesrogenia was determined up to 36 months of monitoring without statistically significant differences between groups of different HE methodic. The main factor was patient’s age in which endocrine, vegetative-vascular disorders and the clinical manifestations of psychosomatic are developed in a larger percentage of significantly earlier in women of late reproductive age.The use of proposed program of therapeutic options after HE with ovarian preservation allowed to provide a tendency of the estradiol, progesterone and testosterone levels normalization, prolactin and cortisol concentrations were close to the reference values. Estradiol concentration in the women in main group increased, although it remained significantly below the age normal indices, and the most significant normalization of theses parameters were determined in women who received hormonal replacement therapy. Clinically positive effect in patients on the severity of neurovegetative and psychoemotional manifestations on the background of differentiated treatment was observed after 3 months from the beginning of therapy.Conclusions. The obtained results suggest that the optimization of the treatment program with the the proposed drugs in women in the groups leads to relative optimization of hormonal status and initiation of compensatory-adaptive responses of the organism, which improves the quality of life and eliminates symptoms of hypoestrogenism.

The non-operative management of primary osteoarthritis.

Osteoarthritis is a syndrome characterised by joint pain, resulting in functional limitation and a decreased quality of life. This chronic condition is one of the major public health problems facing society today and is likely to become more prevalent. The expected increase is because of the primary causative factors, advancing age and obesity, becoming increasingly prevalent in society. The diagnosis of osteoarthritis can be made clinically when activity related joint pain is present, alongside morning joint stiffness that lasts for less than 30 minutes. However, a radiological diagnosis can also be made. This article examines the current management strategies, as outlined by the National Institute for Health and Care Excellence guidelines for osteoarthritis. Although numerous surgical options are available, this article focuses on the non-operative strategies currently used. The emphasis in this article is on general principles of treatment rather than treatment options for specific joints.

Which patient-reported outcomes do rheumatology patients find important to track digitally? A real-world longitudinal study in ArthritisPower

BackgroundPatient-reported outcomes (PROs) are increasingly used to track symptoms and to assess disease activity, quality of life, and treatment effectiveness. It is therefore important to understand which PROs patients with rheumatic and musculoskeletal disease consider most important to track for disease management.MethodsAdult US patients within the ArthritisPower registry with ankylosing spondylitis, fibromyalgia syndrome, osteoarthritis, osteoporosis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus were invited to select between 3 and 10 PRO symptom measures they felt were important to digitally track for their condition via the ArthritisPower app. Over the next 3 months, participants (pts) were given the option to continue tracking their previously selected measures or to remove/add measures at 3 subsequent monthly time points (month [m] 1, m2, m3). At m3, pts prioritized up to 5 measures. Measures were rank-ordered, summed, and weighted based on pts rating to produce a summary score for each PRO measure.ResultsAmong pts who completed initial selection of PRO assessments at baseline (N = 253), 140 pts confirmed or changed PRO selections across m1–3 within the specified monthly time window (28 days ± 7). PROs ranked as most important for tracking were PROMIS Fatigue, Physical Function, Pain Intensity, Pain Interference, Duration of Morning Joint Stiffness, and Sleep Disturbance. Patient’s preferences regarding the importance of these PROs were stable over time.ConclusionThe symptoms that rheumatology patients prioritized for longitudinal tracking using a smartphone app were fatigue, physical function, pain, and morning joint stiffness.

Case Report: Sapho Syndrome Previously Mistaken for Paget's Disease

SAPHO syndrome is a rare clinical entity, an acronym named for its frequent coincident clinical manifestations, synovitis, acne, pustulosis, hyperostosis, and osteitis. Its clinical phenotype is widely heterogeneous, which coupled with its rarity causes many misdiagnoses. Herein, we present a case of a patient that was previously diagnosed with Paget’s disease. After an MVA, the full extent of his disease was detected via incidental imaging, which demonstrated sclerosis and ankylosis of the lumbar spine, sclerosis of the clavicles, and the pathognomonic bull’s head configuration on bone scan. Upon further questioning, the patient also harbored intermittent palmar pustulosis, psoriasis, sternoclavicular pain and tenderness, and widespread morning joint stiffness that ameliorates with activity. A high index of suspicion, and knowledge of its variable manifestations are paramount to arrive at a SAPHO diagnosis and thereby provide appropriate therapy to the patient.

Physical Therapy in Rheumatoid Arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic and progressive inflammatory process resulting in the destruction of articular and periarticular tissues and leading to the development of functional impairment, permanent deformities and disability. RA affects approximately 1% of the global population and is more common in women than men. Aim: To assess the effects of physical therapy in RA patients. Material and Methods: The study assessed 21 patients with stage III/IV RA. They were managed with physical therapy, including thermotherapy, electrotherapy, laser therapy, magnetic field therapy and light therapy. The data collected in the study were statistically analysed. Results: After treatment, all study patients showed pain reduction, improved well-being, reduced duration of morning joint stiffness, improved ranges of motion in the joints and a better quality of life. Conclusions: 1. Rheumatoid arthritis is a difficult clinical and social problem. 2. The physical therapy used in the study reduced the pain experienced by the patients and the duration of morning joint stiffness and improved the ranges of motion and quality of life. 3. Physical therapy and rehabilitation constitute the main method of treatment of this disorder.

Patient-reported outcomes from a randomized, double-blind, placebo controlled, phase III study of baricitinib versus placebo in patients with moderately to severely active rheumatoid arthritis and an inadequate response to methotrexate therapy: results from the RA-BALANCE study.

Introduction:To assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX).Methods:This was a 52-week, randomized, double-blind, placebo controlled, phase III study in patients with RA who had an inadequate response to MTX. Patients (n = 290) receiving stable background MTX were randomly assigned (1:1) to receive placebo or baricitinib 4 mg once daily with a primary endpoint at week 12. PROs assessed included Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient’s Global Assessment of Disease Activity, patient’s assessment of pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), European Quality of Life-5 Dimensions-5 Level index scores and visual analogue scale, and measures collected in electronic patient daily diaries: duration of morning joint stiffness, Worst Tiredness, and Worst Joint Pain. Treatment comparisons were made with logistic regression and analysis of covariance models for categorical and continuous variables, respectively.Results:Statistically significant (p ⩽ 0.05) improvements in all PROs were observed in the baricitinib 4 mg group compared to placebo as early as week 1 to week 4; and were sustained to week 24. These improvements were maintained until week 52 for the baricitinib group. A significantly larger proportion of patients met or exceeded the minimum clinically important difference for HAQ-DI (⩾0.22) and FACIT-F (3.56) profiles in the baricitinib group.Conclusion:Baricitinib provided significant improvements in PROs compared to placebo to 52 weeks of treatment in patients with RA who had an inadequate response to MTX.Clinicaltrials.gov identifier: https://clinicaltrials.gov/ct2/show/NCT02265705; NCT02265705; RA-BALANCE. Registered 13 October 2014

Efficacy and Safety of Baricitinib in Chinese Rheumatoid Arthritis Patients and the Subgroup Analyses: Results from Study RA-BALANCE.

IntroductionBaricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK 2, which has demonstrated significant efficacy in patients with moderately to severely active rheumatoid arthritis (RA). This analysis aims to describe the efficacy and safety of baricitinib in Chinese RA patients with an inadequate response to methotrexate (MTX-IR), and to analyze the effects of baseline characteristics on the efficacy of baricitinib treatment.MethodsIn this 52-week, randomized, double-blind, placebo-controlled study, 231 Chinese patients with moderately to severely active RA who had MTX-IR were randomly assigned to placebo (n = 115) or baricitinib 4 mg once daily (n = 116). The primary endpoint was American College of Rheumatology 20% (ACR20) response at week 12. Other efficacy measures included ACR50, ACR70, Physician’s Global Assessment of Disease Activity, Patient’s Global Assessment of Disease Activity, patient’s assessment of pain, Disease Activity Score in 28 joints using high-sensitivity C-reactive protein, remission and low disease activity rates according to Simplified Disease Activity Index or Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, and mean duration and severity of morning joint stiffness, worst tiredness and worst joint pain were analyzed. Additionally, subgroup analyses were performed across baseline characteristics.ResultsStatistically significant improvement in ACR20 response was achieved with baricitinib at week 12 (53.4 vs. 22.6%, p = 0.001) in Chinese patients, compared to placebo. Most of the secondary objectives were met with statistically significant improvements. Efficacy of baricitinib was irrespective of patient demographics and baseline characteristics. Safety events were similar between the baricitinib and placebo groups.ConclusionsThe efficacy of baricitinib 4 mg in Chinese patients with moderately to severely active RA and prior MTX-IR was clinically significant compared to placebo regardless of baseline characteristics. Baricitinib was well tolerated with an acceptable safety profile during the full study period.Trial RegistrationNCT02265705Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-020-00231-6) contains supplementary material, which is available to authorized users.

EP30 Understanding which patient-reported outcomes are important to rheumatology patients: findings from ArthritisPower

Abstract Background Little is known about PRO measures patients find most important for disease, treatment effectiveness/health outcomes. In this study, we examined PROs selected by patients with rheumatologic conditions to further elucidate which disease symptoms they found most important to track within ArthritisPower registry. As the study is ongoing, we discuss initial PRO selections of study participants. Methods Adult US patients with self-reported rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), osteoporosis (OP), osteoarthritis (OA), fibromyalgia syndrome (FMS) in ArthritisPower were invited to participate and prompted to select up to ten PRO (symptom) measures they felt were important to track their condition at baseline via ArthritisPower smartphone and Web-based app. PROs Measurement Information System (PROMIS) instruments focusing on symptoms of pain, physical and cognitive function, mental health, fatigue, social function, work impact, sexual function, and sleep, and Outcomes Measures in Rheumatology (OMERACT) RA flare instrument (only for those with RA) and Lilly-developed morning joint-stiffness duration question were offered. At Month (m)1, m2, m3, participants were given the option to continue tracking their selected PRO measures or change. At m3, participants complete an exit survey prioritizing all measures selected during participation and specifying other symptoms not available they would have wanted to track. Descriptive statistics were conducted on baseline data. Results As of May 2019, 292 participants enrolled (251 completed baseline assessments). Mean age was 55.6 (9.2) years, 89.6% female, 91.2% White, mean disease duration of 12 (10.7) years; similar to the overall ArthritisPower population. Majority (64.1%) self-reported OA, followed by RA (49.0%), FMS (40.6%), PsA (26.3%), OP (20.3%), AS (15.5%), SLE (5.6%), not mutually exclusive. Top 3 PRO domains chosen at baseline were fatigue, mental health, pain (Table 1). Average number of instruments selected for baseline completion was 6.9 (2.4). Conclusion Participants prioritised tracking fatigue, aspects of mental health, pain, physical function, social function, sleep, morning stiffness. These findings provide insights into symptoms rheumatology patients find most important; useful to inform the design of future patient-centric clinical trials and real-world evidence generation. Disclosures T. Daud (Non-Author Presenter) None. W.B. Nowell: Shareholder/stock ownership; WN has Ownership Interest (stocks, stock options, or other ownership interest excluding diversified mutual funds). C.L. Kannowski Corporate appointments; CLK is an employee of Eli Lilly and Company. Shareholder/stock ownership; CLK owns stock options at Eli Lilly and Company. K. Gavigan: None. Z. Cai: Corporate appointments; ZC is an employee of Eli Lilly and Company. Shareholder/stock ownership; shareholder of Eli Lilly and Company. A. Cardoso: Corporate appointments; AC is an employee of Eli Lilly and Company. Shareholder/stock ownership; AC is a stockholder of Eli Lilly and Company. T. Hunter: Corporate appointments; TH is an employee of Eli Lilly and Company. Shareholder/stock ownership; TH is a shareholder of Eli Lilly and Company. J. Birt: Corporate appointments; JB is an employee of Eli Lilly and Company. Shareholder/stock ownership; JB is a shareholder of Eli Lilly and Company. J. Workman: Corporate appointments; JW is an employee of Eli Lilly and Company. J. Curtis: Consultancies; JC has received Consulting Fees from AbbVie, Amgen, BMS, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, UCB. Grants/research support; JC has received grants/research support from AbbVie, Amgen, BMS, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, UCB.

Important determinants of the patient choice between TNF- vs. non-TNF Biologic disease-modifying anti-rheumatic drugs (DMARDs) for active rheumatoid arthritis (RA).

To assess why patients choose TNF- versus non-TNF biologics for treating active rheumatoid arthritis (RA) after methotrexate-failure. Participants responded to the question "What sort of things help a patient decide the treatment choice between the two types of injectable biologics, TNF biologic versus non-TNF biologic, for treating active rheumatoid arthritis when methotrexate fails to control RA disease activity?" They nominated responses, discussed and then voted. Forty-four patients participated in 10 nominal groups (Birmingham; n=6; New York City: n=4), who were predominantly female (86%), 68% white, with a mean age of 65 (standard deviation [SD], 12) years. Present/past DMARDs included methotrexate in 91%, glucocorticoids in 11%, and biologics and/or Jak-inhibitors in 68% of participants. Pain and fatigue were mild-moderate with means of 3.9 (SD, 2.5) and 4.3 (SD, 2.5), respectively, on 0-10 scale; mean morning joint stiffness was 1.3hours (SD, 2.1). The number of groups that nominated each response and total votes were as follows: (1) Side effects/fear of side effects: 10/10; 31% votes (82/264); (2) Efficacy/ability to reduce joint damage: 9/10; 30% votes (80/264); (3) Doctor's opinion, 6/10; 12% votes (32/264); (4) Cost, 7/10; 9% votes (25/264); (5) Other drugs/comorbidity, 4/10; 12% votes (31/264); (6) Experience of others/information-seeking/own research, 2/10; 2% votes (5/264); (7) Newness, 1/10; 2% votes (6/264); and (8) Convenience/frequency of use, 1/10; 1% votes (3/264). We identified the patient perspective of choice between TNF versus non-TNF biologic for treating active RA. This knowledge can help in informative shared decision-making in clinical care.

Effects of Treatment at a Medical Resort on the Quality of Life in Patients with Rheumatoid Arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the connective tissue that damages articular and periarticular tissue and leads to the development of permanent deformities and disability. Aim: To assess the quality of life of rheumatoid arthritis patients after treatment at a medical resort. M aterial and Methods: The study assessed 30 patients with rheumatoid arthritis treated at a medical hospital in Busko-Zdrój. The study group consisted of 18 women and 12 men over the age of 50 years. The patients underwent sulphide/hydrogen sulphide baths and physical therapy procedures. The data collected in the study was statistically analysed using Excel; calculations were performed with the SPSS Statistica 21.0 software. A chi-squared test was used to assess statistical correlations between variables. Results: After spa hospital treatment, all patients reported reduced pain, improved well-being, reduced duration of morning joint stiffness, and improved independence; the pain-free walking distance markedly increased. The treatment had a beneficial influence on the quality of life of study patients. Conclusions: 1. Rheumatoid arthritis is a difficult clinical and social problem. 2. The balneotherapy and physical therapy used in the study reduced the duration of morning joint stiffness and pain experienced by the patients. 3. The balneotherapy and physical therapy used in the study had a positive effect on the ability to ambulate, increasing the pain-free walking distance, and improving the quality of life.

Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT

BackgroundTo evaluate the effect of upadacitinib on patient-reported outcomes (PROs) in patients with RA who had an inadequate response to csDMARDs.MethodsPatients in SELECT-NEXT, a randomised controlled trial, were on a background of csDMARDs and received upadacitinib 15 mg and 30 mg or placebo daily for 12 weeks. PROs included Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), duration and severity of morning (AM) joint stiffness, Short Form 36 Health Survey (SF-36), and Work Instability Scale for RA (RA-WIS). Least squares mean (LSM) changes were based on mixed-effect repeated measure models. Percentages of patients reporting improvements ≥ minimum clinically important differences (MCIDs) and scores ≥ normative values and number needed to treat (NNT) were determined; group comparisons used chi-square tests.ResultsData from 661 patients were analysed. Compared with placebo, patients receiving upadacitinib reported statistically significant improvements (both doses, P < 0.05) in PtGA, pain, HAQ-DI, FACIT-F, duration and severity of AM stiffness, SF-36 (PCS and 6/8 domains), and RA-WIS at week 12. Significantly, more upadacitinib-treated patients (both doses, P < 0.05) reported improvements ≥ MCID in PtGA, pain, HAQ-DI, FACIT-F, AM stiffness, SF-36 (PCS and 4 or 7/8 domains), and RA-WIS and scores ≥ normative values in HAQ-DI, FACIT-F, and SF-36 (PCS and 4 or 5/8 domains). For most PROs, the incremental NNT with upadacitinib to report clinically meaningful improvement from baseline ranged from 4 to 8 patients.ConclusionsUpadacitinib 15 mg or 30 mg daily for 12 weeks resulted in significant and clinically meaningful improvements in global disease activity, pain, physical function, fatigue, duration and severity of AM stiffness, HRQOL, and work instability among csDMARD-IR patients with RA.Trial registrationClinicaltrials.gov, NCT02675426. Retrospectively registered 5 February 2016.

Expressions of circadian clock genes represent disease activities of RA patients treated with biological DMARDs

Objectives: Rheumatoid Arthritis (RA) is the autoimmune disease representing the circadian variations of symptoms such as morning stiffness of joints or increased production of cytokines around midnight. Clock genes have been reported to affect on the pathogenesis of RA, however, the detailed relation between clock genes and disease activities of RA has remained unclear.Methods: In this study, 15 RA patients treated with biological disease modifying anti-rheumatic drugs (bDMARDs) were enrolled (TNF inhibitor, 5; IL-6 inhibitor, 5; CTLA4-IgG, 5). Blood samples were collected from RA patients before treatment and at the study end-point fulfilling DAS28-ESR < 3.2. Total RNA was extracted from leukocytes to examine the expressions of the clock genes. We then evaluated the correlation of the clock gene expression with disease activity and the diagnostic values of the clock genes.Results: The expressions of the clock genes were significantly modulated by bDMARDs treatments. Disease activities were significantly correlated with the clock genes expressions, and disease remission/low disease activity could be distinguished from moderate/high disease activity due to the sensitivities, the specificities and the areas under the curves of that.Conclusion: The expressions of the clock genes in leukocytes could be useful as novel biomarkers predicting disease activities and therapeutic efficacies for bDMARDs in RA treatments.