Severity Of Morning Stiffness Research Articles

Responsiveness and sensitivity of PROMs to change in disease activity status in early and established rheumatoid arthritis.

To determine whether patient reported outcome measures (PROMs) capturing activity limitations, health impact, pain, fatigue and work ability are responsive and sensitive to changes in disease activity status in patients with early and established rheumatoid arthritis (RA). All early RA patients (n = 557) from the tREACH-trial and established RA patients (n = 188) from the TARA-trial were included. Both studies were multicentre, single-blinded trials with a treat-to-target management approach. The following PROMs were studied: Health Assessment Questionnaire Disability Index(HAQ-DI), morning stiffness severity, EQ-5D, general health, 36-item short form(SF-36), joint pain, fatigue and productivity loss. Mean changes in PROMs between two consecutive visits were compared with changes in disease activity status(remission, low disease activity and active disease) using linear mixed models and standardised response means. Additionally, the proportion of individual observations that showed an expected PROM response to disease activity status alterations was calculated. HAQ-DI, morning stiffness severity, general health, EQ-5D and joint pain demonstrated responsiveness to improvement or worsening of disease activity status in both early and established RA. SF-36 physical and mental component scale, fatigue and productivity loss did not show this effect in both groups. Across nearly all PROMs, the magnitude of change and the proportion of individual observations that reflect a shift from and to active disease remained low. HAQ-DI, morning stiffness severity, EQ-5D, general health and joint pain are responsive to disease activity status alterations on a group level in both early and established RA. For the individual patient the responsiveness of these PROMs is poor. tREACH trial (www.isrctn.com, ISRCTN26791028) and TARA trial (www.onderzoekmetmensen.nl, NTR2754).

Positive and Negative Effects of Administering a Magnetic Field to Patients with Rheumatoid Arthritis (RA).

Background: Magnetotherapy applied to patients with rheumatoid arthritis (RA) produces anti-inflammatory, analgesic and antioedema effects. Observations suggest that the beneficial and adverse effects of magnetotherapy are related to the parameters of the magnetic field applied. This study aimed to assess the positive and negative effects of magnetotherapy, taking into account the type of the field. Methods: This study involved 39 patients with RA, who were randomly assigned to two groups: SMF-static magnetic field (n = 18) and PEMF-low-frequency pulsed electromagnetic field (n = 21). The examinations carried out before and after the therapy included a general assessment of the functional status, assessment of pain severity, measurement of the duration and severity of morning stiffness, computer-aided measurement of the range of motion of the hand joints and measurement of the hand volume using water displacement method. The patients received kinesiotherapy and magnetotherapy, as determined by the randomisation. Results: The findings show improved functional status by 0.26 points on average (p = 0.0166) measured with the Health Assessment Questionnaire (HAQ-20), reduced pain by 2.2 points on average (p = 0.0000) on the Visual Analogue Scale (VAS), decreased duration of morning stiffness by 23.2 min on average (p = 0.0010) and reduced severity of morning stiffness by 15.2 points on average (p = 0.0010). The assessment of the dominant hand showed improved range of motion by 1.9 mm on average (p = 0.0036) and reduced volume by 0.9 mm3 on average (p = 0.0230). A significantly reduced duration and severity of morning stiffness was observed in the SMF group. Statistically significant changes in the HAQ-20 scores, range of motion and the volume of the dominant hand were identified in the PEMF group. Conclusions: Magnetic fields improved the functional status and reduced pain, morning stiffness and swelling in the hand. A static magnetic field may be more effective in reducing morning stiffness, whereas a pulsed magnetic field may, to a greater extent, improve function and reduce swelling in the rheumatoid hand. The effects of magnetotherapy reported so far require further observation.

Is it possible to objectively determine morning stiffness in rheumatoid arthritis?

Objectives: This study aimed to objectively and quantitatively exhibit morning stiffness by using electrophysiological methods. Patients and methods: The prospective, controlled study was conducted with 52 participants between February 2013 and February 2014. Of the participants, 26 were recruited among RA patients (3 males, 23 females; mean age: 55.9±11.2 years; range, 24 to 74 years) followed at the rheumatology clinic, and 26 were healthy subjects (4 males, 22 females; mean age: 54.9±8.3 years; range, 41 to 70 years) for the control group. Duration and severity of morning stiffness were recorded for all participants. Activity of disease and functional status were evaluated by the Disease Activity Score 28 and Health Assessment Questionnaire (HAQ), respectively. Electrophysiological reaction times, severity of pain (Visual Analog Scale), HAQ, and grip strength were measured for each participant twice in 24 h in the morning (08:00-09:00 am) and afternoon (03:00-05:00 pm). Results: In the RA group, motor reaction and response times and severity of pain values were significantly lower in the afternoon compared to the morning (p=0.030, p=0.031, and p=0.002, respectively), and hand grip strengths were significantly higher in the afternoon (p=0.007). In the control group, no change was observed between morning and afternoon measurements in the strength and reaction time variables. Conclusion: Our hypothesis that stiffness would slow down the movements in the morning in RA was supported by the prolonged motor and response times in the morning compared to the afternoon. However, in the control group (no morning stiffness), there was no difference in reaction time variables between the morning and afternoon, objectively demonstrating the concept of morning stiffness in this study.

P127 Baricitinib Efficacy in Moderate Rheumatoid Arthritis - A Post-hoc Analysis from two Phase III Trials

Abstract Background/Aims Baricitinib, an oral selective JAK 1/2 inhibitor, is approved for treating adults with moderate-to-severe active rheumatoid arthritis (RA). This analysis aims to report the efficacy of baricitinib in patients with moderate RA at weeks (W)12 and 24 from two phase III studies, RA-BEAM (NCT01710358) and RA-BUILD (NCT01721057). Methods This post-hoc analysis included patients from RA-BEAM (inadequate responders to methotrexate) and RA-BUILD (inadequate responders to conventional synthetic DMARDs) with moderate RA at baseline (defined as Disease Activity Score (DAS)-28 with C-reactive protein (CRP) of > 3.2 and ≤5.1). This analysis reports treatment response as low disease activity (LDA) defined by DAS28-CRP ≤3.2 and >2.6 or remission defined by < 2.6 and presents descriptive data at W12 and W24, including pain (visual analogue scale [VAS]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), physical functioning (Health Assessment Questionnaire-Disability Index [HAQ-DI]), Work Productivity and Activity Impairment (WPAI), duration and severity of morning stiffness, joint pain, and fatigue using daily diaries. Continuous variables are presented as median with interquartile range and categorical variables as frequencies and percentages. Results At baseline, moderate RA was observed in 117 patients on baricitinib 4-mg, 80 on adalimumab, and 133 on placebo in RA-BEAM; and 80 on baricitinib 2-mg, 63 on baricitinib 4-mg, and 73 on placebo in RA-BUILD. In RA-BEAM at W12, 46.2%, 37.5%, and 9.0% of patients on baricitinib 4-mg, adalimumab, and placebo, respectively, achieved remission. In RA-BUILD at W12, 38.8%, 44.4%, and 13.7% of patients on baricitinib 2-mg, baricitinib 4-mg, and placebo, respectively, achieved remission. At W24, a further increase in the percentage of patients achieving remission was reported in both trials (Table). Improvement in pain (VAS), FACIT-F, and HAQ-DI was similar across RA-BEAM and RA-BUILD with baricitinib treatment (Table). In both trials, patients reported improvement in duration and severity of morning stiffness, worst tiredness, and worst joint pain with baricitinib treatment (Table). Additionally, baricitinib treatment yielded numerical improvement in impairment of daily activity and work productivity in RA-BEAM (Table). Conclusion In patients with moderate RA, baricitinib markedly improved signs and symptoms of RA and patient-reported outcomes (PROs) at W12 and W24. Disclosure B.W. Kirkham: Member of speakers’ bureau; B.K. has received speaker’s payments from AbbVie, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer, and UCB. Grants/research support; B. K. has received research support from Eli Lilly and Company and Novartis. Other; B. K. has been an adviser for AbbVie, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer, and UCB. B. W. has received meeting support payments from Eli Lilly and Company. E. Nikiphorou: Honoraria; E.N. received speaker honoraria from Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Eli Lilly and Company, and Fresenius. Grants/research support; E.N. holds grants from Pfizer and Eli Lilly and Company. Other; E.N. participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Eli Lilly and Company, and Fresenius. E. N. received travel payments from Eli Lilly and Company. C.J. Edwards: Honoraria; C.E received honoraria from Eli Lilly and Company. Grants/research support; C.E. received grant payments from Abbvie, Pfizer, Roche, Biogen, and Eli Lilly and Company. Other; C.E. received personal fees from Abbvie, Astra-Zeneca, BMS, Celltrion, Fresenius, Galapagos, Gilead, GSK, Janssen, Roche, Pfizer, and Sanofi and travel and meeting payments from Eli Lilly and Company. M. Sheesh: Corporate appointments; M. S. is a full-time employee at Eli Lilly and Company. Shareholder/stock ownership; M. S. is a minor shareholder at Eli Lilly and Company. E. Haladyj: Corporate appointments; E. H. is a full-time employee at Eli Lilly and Company. Shareholder/stock ownership; E. H. is a minor shareholder at Eli Lilly and Company. J. Gerwien: Corporate appointments; J. G. is a full-time employee at Eli Lilly and Company. Shareholder/stock ownership; J. G. is a minor shareholder at Eli Lilly and Company. L. Zaremba-Pechmann: Corporate appointments; L. Z-P is a contractor at HaaPACS gmbH. P.C. Taylor: Consultancies; P. T. has been a consultant for AbbVie, Biogen, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli Lilly and Company, BMS, Pfizer, Roche, Celltrion, Sanofi, Nordic Pharma, Fresenius, and UCB. Grants/research support; P. T. received grant/research support from Galapagos. Other; P. T. has received meeting support payments from Eli Lilly and Company.

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.

Prolonged morning stiffness is common in hand OA and does not preclude a diagnosis of hand osteoarthritis

Prolonged morning stiffness (>60min) is considered a symptom of inflammatory arthritis, but has a poor discriminative ability. Knowledge about morning stiffness in patients with hand osteoarthritis (OA) is lacking. We therefore studied morning stiffness in patients with hand OA. Patients with primary hand OA according to their treating rheumatologist in the Hand OSTeoArthritis in Secondary care (HOSTAS) cohort were studied. Severity of morning stiffness was examined with Australian/Canadian hand OA index (AUSCAN) and presence and duration of morning stiffness were examined with a standardized questionnaire. Association of patient and disease characteristics with prolonged morning stiffness (>60min) were analyzed with logistic regression. In total 519 of 538 patients had available data about duration of morning stiffness, of whom 89 (17%) had prolonged morning stiffness. Severity of stiffness was mild in 158 of 525 (30%), intermediate in 194 (37%), severe in 97 (18%) and extreme in 19 (4%) patients. Patients with prolonged morning stiffness reported more pain, worse physical function and had a reduced mental and physical quality of life. Patients with prolonged morning stiffness also had more severe radiographic disease, although the association did not reach statistical significance. Prolonged and severe morning stiffness are frequently present in patients with hand OA. Patients with these symptoms report more pain in general and have a lower quality of life than patients that do not report these symptoms. Prolonged morning stiffness does not preclude a diagnosis of hand OA.

Back pain and assessment of ankylosing spondylitis activity during gestation: symptoms reflecting exacerbation of the disease and pregnancy

Objective: to study the dynamics of back pain severity and the frequency of its individual components, characterizing the inflammatory and mechanical rhythm, on the background of gestation in women with ankylosing spondylitis (AS) and compare them with manifestations of dorsopathy in healthy pregnant women; to determine the information value of BASDAI during pregnancy, i.e. to identify its components with the optimal sensitivity and specificity ratio for assessing AS activity during gestation.Patients and methods. The main group consisted of 49 pregnant women with AS who met the modified New York criteria of 1984. The average age of patients was 31.7±4.9 years, the average duration of the disease was 134.4±85.8 months. BASDAI for trimesters of pregnancy was: 2.3 [1.2; 4.4], 2.8 [1.4; 4.2] and 2.2 [1.6; 4.0]. The control group included 51 pregnant women with back pain associated with gestation, without rheumatic diseases. The average age was 28.0±4.4 years. The intensity of back pain was assessed on a numerical rating scale. ROC-analysis was performed with calculation of the area under the curve (AUC) of each component of BASDAI in each pregnancy trimester.Results and discussion. More than 80% of pregnant women with AS experienced back pain, while the intensity of general back pain did not differ from that in the control group. Night back pain with improvement on awakening in the main group was present in 70%, 58% and 68.8% of women, respectively, in the I-III trimesters; its intensity was 3 [1; 5], 3.5 [3; 6] and 3.4 [2; 5] respectively; the frequency and severity of night pain were higher than in the control group. The number of women with improvement after exercise in the II and III trimesters did not differ in both groups. In the second half of pregnancy, 40% of AS patients noted improvement during rest, 52.1% – increased pain after exercise; the frequency of mechanical rhythm pain elements remained lower than in the control group. The AUC value for BASDAI in the first trimester was 0.74; AUC of all BASDAI components was >0.5. In the II and III trimesters, the AUC values for fatigue and back pain were 0.8.Conclusion. During pregnancy the vast majority of women with AS experience back pain, the nature of which changes in the second half of gestation. Night pain that improves on awakening reflects AS activity and is not related to pregnancy. The BASDAI components of severity and duration of morning stiffness have the highest classification value during pregnancy.

AB0789 What drives the BASDAI in pregnant patients with axial spondyloarthritis? A pooled analysis of four European pregnancy registries.

BackgroundThe patient reported Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) includes the six components fatigue, neck, back or hip pain, pain or swelling in other joints, tenderness, morning stiffness severity and duration on a 0-10 scale.ObjectivesTo explore the driving factors for the BASDAI in pregnant patients with axial spondyloarthritis (axSpA).MethodsAnonymized pooled data of the European Network of Pregnancy Registries in Rheumatology (EuNeP) were used. The four participating registries are located in France, Germany, Norway and Switzerland, and collect data of women with child wish, during and after pregnancy prospectively and nationwide on regular time points. For the analysis, women who fulfilled ASAS classification criteria for axSpA and for whom a pregnancy outcome was reported until 12/2019 or 07/2020, depending on the registry, were selected. Mean BASDAI and its components were analysed descriptively.ResultsA total of 332 pregnancies from 304 women with axSpA were eligible. The Norwegian registry contributed half of the pregnancies (50.3%), followed by Germany (26.2%), France (15.4%) and Switzerland (8.1%). Mean maternal age was 31 years, the average disease duration 5 years.Mean BASDAI was 3.0 before conception, 3.4, 3.4 and 3.5 in the 1st, 2nd and 3rd trimester, and 3.4 within 6 months postpartum. The figure shows mean values of the BASDAI and its individual components in the different time periods. Fatigue was higher than the mean score during all phases, and especially elevated in the 1st and 3rd trimester. Furthermore, values for neck, back or hip pain were higher than the mean score, especially from 2nd trimester on. All other components were lower than the mean score.Data were not reported for all pregnancies and all time periods. Availability was highest in the 2nd and 3rd trimester with reported BASDAI in 60% and 62% of the pregnancies, respectively. Lowest reporting was 24% in the preconception period because only a part of the women was also observed before pregnancy.ConclusionThe BASDAI is a validated instrument for assessing disease activity in patients with axSpA. Since the calculation of the score also includes factors that can be influenced by pregnancy, it may only be of limited value for measuring disease activity in pregnancy. This analysis shows that mainly fatigue and back pain in particular have an impact on the mean BASDAI. A limitation of this analysis is that data were not available for all measured time points of the individual pregnancies. Therefore, the results should be confirmed by other studies.Figure 1.Means of BASDAI components before, during and after pregnancy (the table presents means ± standard deviation).AcknowledgementsThis work was supported by a research grant from FOREUM Foundation for Research in Rheumatology.Disclosure of InterestsYvette Meissner Speakers bureau: Pfizer, Anna Moltó Consultant of: UCB and BioGen, Grant/research support from: UCB, Nathalie Costedoat-Chalumeau Grant/research support from: to my institution (UCB), Rebecca Fischer-Betz: None declared, Frauke Förger Speakers bureau: UCB pharma, GSK, Consultant of: UCB pharma, GSK, Roche, Grant/research support from: UCB pharma, GSK, Marianne Wallenius: None declared, Anja Strangfeld Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, Pfizer, Roche, Sanofi, UCB.

Patient-reported outcomes of upadacitinib versus abatacept in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying antirheumatic drugs: 12- and 24-week results of a phase 3 trial

BackgroundIn previous clinical trials, patients with active rheumatoid arthritis (RA) treated with upadacitinib (UPA) have improved patient-reported outcomes (PROs). This post hoc analysis of SELECT-CHOICE, a phase 3 clinical trial, evaluated the impact of UPA vs abatacept (ABA) with background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on PROs in patients with RA with inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR).MethodsPatients in SELECT-CHOICE received UPA (oral 15 mg/day) or ABA (intravenous). PROs evaluated included Patient Global Assessment of Disease Activity (PtGA) by visual analog scale (VAS), patient’s assessment of pain by VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), morning stiffness duration and severity, 36-Item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Impairment (WPAI), and EQ-5D 5-Level (EQ-5D-5L) index score. Least squares mean (LSM) changes from baseline to weeks 12 and 24 were based on an analysis of covariance model. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCID) were compared using chi-square tests.ResultsData from 612 patients were analyzed (UPA, n=303; ABA, n=309). Mean age was 56 years and mean disease duration was 12 years. One-third received ≥2 prior bDMARDs and 72% received concomitant methotrexate at baseline. At week 12, UPA- vs ABA-treated patients had significantly greater improvements in PtGA, pain, HAQ-DI, morning stiffness severity, EQ-5D-5L, 2/4 WPAI domains, and 3/8 SF-36 domains and Physical Component Summary (PCS) scores (P<0.05); significant differences persisted at week 24 for HAQ-DI, morning stiffness severity, SF-36 PCS and bodily pain domain, and WPAI activity impairment domain. At week 12, significantly more UPA- vs ABA-treated patients reported improvements ≥MCID in HAQ-DI (74% vs 64%) and SF-36 PCS (79% vs 66%) and 4/8 domain scores (P<0.05).ConclusionsAt week 12, UPA vs ABA treatment elicited greater improvements in key domains of physical functioning, pain, and general health and earlier improvements in HAQ-DI. Overall, more UPA- vs ABA-treated patients achieved ≥MCID in most PROs at all timepoints; however, not all differences were statistically significant. These data, however, highlight the faster response to UPA treatment.Trial registrationNCT03086343, March 22, 2017.

Determinants of the patient global assessment of well-being in early axial spondyloarthritis: 5-year longitudinal data from the DESIR cohort.

ObjectivesTo investigate the determinants of patient well-being over time, and the influence of age, gender and education in patients with early axial spondyloarthritis (axSpA).MethodsFive-year data from DESIR, a cohort of early axSpA, were analysed. The outcome was the BAS-G over 5 years. Generalized estimating equations (GEE) were used to test the relationship between potential explanatory variables from five outcome domains (disease activity, physical function, spinal mobility, structural damage and axial inflammation) and BAS-G over time. Longitudinal relationships were analysed using an autoregressive GEE model. Age, gender and educational level were tested as effect modifiers or confounders.ResultsA total of 708 patients were included. Higher BASDAI questions on fatigue [β (95% CI): 0.17 (0.13, 0.22)], back pain [0.51 (0.46, 0.56)], peripheral joint pain [0.08 (0.04, 0.12)] and severity of morning stiffness [0.08 (0.03–0.13)], and higher BASFI [0.14 (0.08, 0.19)] were associated with a higher BAS-G. In the autoregressive model, the same variables except for morning stiffness were associated with a worsening in BAS-G. Age, gender and educational level were neither effect modifiers nor confounders.ConclusionA higher level of back pain is associated with a worsening of patient well-being, as are, though to a lesser extent, higher levels of fatigue, peripheral joint pain and physical disability. Age, gender and educational level do not have an impact on these relationships.

Predictors of fatigue and persistent fatigue in early rheumatoid arthritis: a longitudinal observational study, data from the ESPOIR cohort

Objective To determine, in a cohort of patients with early rheumatoid arthritis (RA), factors associated with fatigue at baseline, describe its evolution over 5 years of follow-up, and determine baseline predictors of persistent fatigue. Method We selected patients fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA included in the ESPOIR cohort. Using bivariable and multivariable logistic regression models, we examined baseline variables associated with baseline fatigue (defined by visual analogue scale fatigue > 20) and baseline predictors of persistent fatigue (if the patient experienced fatigue at all visits during the 5 year follow-up period). Results We analysed 673 patients; 80.7% reported fatigue at baseline. At baseline, fatigue was associated with female gender, younger age, greater severity of morning stiffness, sleep problems, higher Health Assessment Questionnaire levels, presence of sicca symptoms, history of thyroid problems, and presence of psychological distress (depressive or anxiety symptoms). At 5 years of follow-up, the percentage of fatigued patients who reported fatigue at all time-points since baseline was 24.6% (referred to as ‘persistent fatigue’). Independent baseline predictors were presence of sicca symptoms, greater severity of morning stiffness, and psychological distress. Conclusions Fatigue is a frequent symptom in RA. The presence of sicca symptoms, greater severity of morning stiffness, and presence of psychological distress at baseline were associated with baseline fatigue and persistent fatigue at 5 years. We did not observe any association between baseline fatigue or persistent fatigue and the Disease Activity Score based on 28-joint count–erythrocyte sedimentation rate.

Rheumatoid Arthritis Morning Stiffness Is Associated With Synovial Fibrin and Neutrophils.

Morning stiffness is a hallmark symptom of rheumatoid arthritis (RA), but its etiology is poorly understood. This study was undertaken to determine whether any histologic features of synovium are associated with this symptom. Data on patient-reported morning stiffness duration and severity, and Disease Activity Score in 28 joints (DAS28) were collected from 176 patients with RA undergoing arthroplasty. Synovium was scored for 10 histopathologic features: synovial lining hyperplasia, lymphocytes, plasma cells, Russell bodies, binucleate plasma cells, fibrin, synovial giant cells, detritus, neutrophils, and mucin. Fibrinolysis of clots seeded with various cell types was measured in turbidimetric lysis assays. Stiffness severity and morning stiffness duration were both significantly associated with DAS28 (P = 0.0001 and P = 0.001, respectively). None of the synovial features examined were associated with patient-reported stiffness severity. The presence of neutrophils and fibrin in RA synovial tissue were significantly associated (P < 0.0001) with patient-reported morning stiffness of ≥1 hour, such that 73% of patients with both synovial fibrin and neutrophils reported morning stiffness of ≥1 hour. Further, neutrophils and fibrin deposits colocalized along the synovial lining. In in vitro analyses, fibrin clots seeded with necrotic neutrophils were more resistant to fibrinolysis than those seeded with living neutrophils or no cells (P = 0.008). DNase I treatment of necrotic neutrophils abrogated the delay in fibrinolysis. In RA, prolonged morning stiffness may be related to impaired fibrinolysis of neutrophil-enmeshed fibrin deposits along the synovial membrane. Our findings also suggest that morning stiffness severity and duration may reflect distinct pathophysiologic phenomena.

Effectiveness and safety study of oral triamcinolone in patients with rheumatoid arthritis in India

INTRODUCTION: This study was conducted to assess the effectiveness and safety of low-dose oral triamcinolone (Kenacort®, Abbott Healthcare Pvt. Ltd) in combination with disease-modifying antirheumatic drugs (DMARDs) in Indian patients with rheumatoid arthritis (RA).MATERIALS AND METHODS: Patients with an established diagnosis of RA, on a stable dose of DMARDs for at least 6-weeks, with evidence of disease flare-up or insufficient response to DMARDs were enrolled. Effectiveness of triamcinolone (4 mg) on disease activity (Disease Activity Score-28 [DAS28]), severity (Visual Analog Scale) and duration of morning stiffness, tender joint count (TJC), swollen joint count (SJC), patient global assessment of disease activity (Health Assessment Questionnaire-Disability Index [HAQ-DI]), quality of life (RAND 36-Item Health Survey score [SF-36]), and safety at 6 and 12 weeks of treatment were assessed.RESULTS: About 98.3% of patients completed the study (119/121; female: 64.5%). A significant improvement in DAS28 score was evident at weeks 6 and 12 compared to baseline (baseline: mean [standard deviation (SD)]: 6.6 (0.9); week 6: mean (SD): 5.5 (0.9); 95% confidence interval difference (CI): −1.3 to −1.0; P < 0.001; week 12: mean [SD]:4.7 [0.7]; 95% CI difference: −2.1 to −1.8; P < 0.001). Severity and duration of morning stiffness also improved significantly at the end of 6 and 12 weeks of treatment (P < 0.001). Substantial improvement in TJC, SJC, HAQ-DI score, and RAND 36-Item score was also evident (P < 0.001). Commonly reported adverse events were gastroesophageal reflux disease (3.3%), headache (3.3%), and fever (2.5%), which were mild and resolved subsequently.CONCLUSION: Low-dose triamcinolone with DMARDs was effective and well-tolerated in Indian patients with RA and in those with evidence of disease flare-up or insufficient response to DMARDs.

Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs

BackgroundPatient-reported outcomes (PROs) are important when evaluating treatment benefits in rheumatoid arthritis (RA). We compared upadacitinib, an oral, selective JAK-1 inhibitor, with placebo to assess clinically meaningful improvements in PROs in patients with RA who have had inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARD-IR).MethodsPRO responses between upadacitinib 15 mg or 30 mg and placebo were evaluated at week 12 from the SELECT-BEYOND trial. Improvement was determined by measuring Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36), duration and severity of morning (AM) stiffness, and Insomnia Severity Index (ISI). Least squares mean changes and percentage of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores greater than or equal to normative values were determined. The number needed to treat (NNT) to achieve clinically meaningful improvements was calculated.ResultsIn 498 patients, both upadacitinib doses resulted in statistically significant changes from baseline versus placebo in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 7 of 8 SF-36 domains (15 mg), 6 of 8 SF-36 domains (30 mg), and AM stiffness duration and severity. Compared with placebo, more upadacitinib-treated patients reported improvements ≥ MCID in PtGA, pain, HAQ-DI, SF-36 PCS, 7 of 8 SF-36 domains (15 mg), 5 of 8 SF-36 domains (30 mg), AM stiffness duration and severity, and ISI (30 mg) and scores ≥ normative values in HAQ-DI and SF-36 domains. Across most PROs, NNTs to achieve MCID with upadacitinib ranged from 4 to 7 patients.ConclusionsIn bDMARD-IR RA patients, upadacitinib (15 mg or 30 mg) improved multiple aspects of quality of life, and more patients reached clinically meaningful improvements approaching normative values compared with placebo.Trial registrationThe trial is registered with ClinicalTrials.gov (NCT02706847), registered 6 March 2016.

Association Between Self-Reported Spinal Morning Stiffness and Radiographic Evidence of Lumbar Disk Degeneration in Participants of the Cohort Hip and Cohort Knee (CHECK) Study.

Low back pain (LBP) is very common and is a main cause of limited activity and work absence. Patients with LBP may also report spinal morning stiffness; this symptom could be useful for identifying subgroups with signs and symptoms related to spinal osteoarthritis. This study investigated whether an association exists between reported spinal morning stiffness and radiographic evidence of lumbar disk degeneration (LDD) in people with LBP and a history of pain of the hip and/or knee. This cross-sectional study used 8-year follow-up data from the Cohort Hip and Cohort Knee study. The association between spinal morning stiffness and radiographic LDD features was assessed with multivariable logistic regression models. The presence of osteophytes was significantly associated with spinal morning stiffness (odds ratio [OR]=2.1 [95% confidence interval [CI]=1.3-3.2]) as was the presence of grade 2 or 3 disk space narrowing (OR=2.0 [95% CI=1.1-3.5]). There was also a significant association between morning stiffness persisting for > 30minutes and grade 2 osteophytes (OR=2.6 [95% CI=1.1-6.2]) and grade 1 disk space narrowing (OR=2.0 [95% CI=1.1-3.6]). Furthermore, there was a significant association between moderate spinal morning stiffness and the presence of osteophytes (OR=2.0 [95% CI=1.2-3.2]). Both the presence of osteophytes and disk space narrowing were significantly associated with severe spinal morning stiffness (for osteophytes: OR=2.0 [95% CI=1.2-3.7]; for narrowing at L1-S1: OR=1.8 [95% CI=1.1-3.1]). Only lumbar lateral radiographs were available for each participant, implying that the LDD features could have been underestimated. The quality of the radiographs was not consistent. This study showed an association between self-reported spinal morning stiffness and symptomatic LDD. When morning stiffness lasted > 30minutes, there was a significant association with the features of LDD. The association was stronger when the severity of spinal morning stiffness increased.

Sexual dysfunction in women in the reproductive age with rheumatoid arthritis: A case-control study

Introduction: Rheumatoid arthritis (RA) is a widespread disease that has a profound effect on the patient’s quality of life.Aim:The aim was to evaluate the rate of sexual dysfunction (SD) in women with RA and to assess the possible association between SD and disease activity, severity of morning stiffness, functional disability and psychological status.Patients and Methods: A case-control study was conducted on 200 sexually active, women in the reproductive age. A total of 100 women with RA attending the rheumatology clinics of two reference hospitals in Upper Egypt and 100 arthritis-free age- and sex-matched healthy controls were compared regarding the scores of Arabic Female Sexual Function Index (ArFSFI) and Hospital anxiety and depression scale (HADS). Additionally, women with RA were evaluated via Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS-28). Results: The mean ages of patients (35.96.4± years) and controls (34.45.4± years) were insignificantly different (P>0.05). Mean FSFI total and domain scores of patients were significantly lower than controls (P<0.001). Overall, 94% of patients and 30% of controls (P<0.001) reported SD. Among women with RA (n: 100), lower SF scores were reported among those with morning stiffness (n: 14, P<0.05). Women with RA who exhibited SD had higher levels of anxiety, depression, and disease activity (P<0.05) than those without SD. However, both subgroups were not different regarding HAQ. Conclusion: The present study found an SD rate of 94% among sexually active women with RA. RA could have an extensively negative effect on all aspects of female sexuality, particularly on lubrication and orgasm dimensions. Moreover, SD in women with RA is significantly associated with disease activity, severity of morning stiffness, depression, and anxiety levels, but not with functional disability (HAQ).

Early and sustained efficacy with apremilast monotherapy in biological-naïve patients with psoriatic arthritis: a phase IIIB, randomised controlled trial (ACTIVE)

ObjectiveEvaluate apremilast efficacy across various psoriatic arthritis (PsA) manifestations beginning at week 2 in biological-naïve patients with PsA.MethodsPatients were randomised (1:1) to apremilast 30 mg twice daily or placebo. At...

Switching From Immediate-Release to Delayed-Release Prednisone in Moderate to Severe Rheumatoid Arthritis: A Practice-Based Clinical Study.

IntroductionRheumatoid arthritis (RA) produces debilitating morning stiffness. Exogenous glucocorticoids can help with these symptoms when timed appropriately. Bedtime dosing of delayed-release prednisone (DR-prednisone) matches the rise of inflammatory cytokines before awakening and can improve stiffness and other RA symptoms. A prospective open-label study was conducted in patients currently on stable doses of immediate-release prednisone (IR-prednisone) who were switched to DR-prednisone to analyze the incremental benefit of better timed and lower dose glucocorticoid therapy.MethodsTwelve US sites enrolled patients with moderate-severe RA into a 12-week prospective study. Patients were switched from IR- to DR-prednisone while maintaining other existing background therapies. Change from baseline in morning stiffness severity, morning stiffness duration, swollen and tender joint counts (S-TJC), 28 joint disease activity score (DAS28), and patient/physician global assessment (PGA/PhGA), among others, were measured. Post-hoc analyses were performed on those completing 10 weeks of treatment and those with >60 min of morning stiffness at baseline.ResultsFifty-six patients had at least one follow-up visit and were similar in demographics to previous controlled trials with DR-prednisone with regard to baseline age and DAS28-CRP but had lower morning stiffness and RA duration. DR-prednisone produced a trend toward lower morning stiffness severity and duration with a reduction in daily prednisone dose of almost 1 mg. Patients treated with DR-prednisone for ≥10 weeks demonstrated significant reductions in morning stiffness duration, SJC, TJC, DAS28-CRP, and PhGA (all p ≤ 0.04). Patients treated for ≥10 weeks with >60 min of baseline morning stiffness produced similar results in these measures as well as a 21% reduction in morning stiffness severity (p = 0.02).ConclusionPatients switched to DR-prednisone from IR-prednisone in this practice-based study maintained or improved their outcomes across a variety of domains, and results were comparable to previous controlled trials in which patients completed at least 10 weeks of treatment.FundingHorizon Pharma USA, Inc.Trial RegistrationClinicalTrials.gov identifier, NCT02287610.

Direct and Indirect Determinants of the Patient Global Assessment in Rheumatoid Arthritis: Differences by Level of Disease Activity.

In rheumatoid arthritis (RA), the patient global assessment (PGA) has been strongly associated with pain severity, but less often with other measures, including disease activity measures. We tested whether RA activity and psychological measures had direct associations with the PGA or indirect associations that were mediated by pain. We also tested whether the correlates of the PGA differed with the degree of RA activity. We studied 260 patients with active RA on 2 visits in a prospective longitudinal study. We used path analysis to test direct and indirect associations of Disease Activity Score in 28 joints (DAS28), morning stiffness, Health Assessment Questionnaire (HAQ), fatigue, physical role limitations, social functioning, depressive symptoms, and health distress with the PGA. Among the 509 visits, the median PGA score was 50 (25th-75th percentile: 24-66). Pain severity had the strongest association with the PGA, but direct associations were also found for morning stiffness severity, health distress, fatigue, and DAS28. Morning stiffness severity, DAS28, health distress, and HAQ were also indirectly associated with the PGA through pain. Among visits with DAS28 ≥5.4, pain, morning stiffness severity, and HAQ were the only determinants of the PGA. Among visits with DAS28 <4.2, health distress and age were additional determinants, and fatigue was marginally associated with the PGA. Although pain was the strongest determinant of the PGA in RA, morning stiffness severity, health distress, fatigue, and DAS28 were also important. Determinants of the PGA differed with RA activity, with health distress, age, and to a lesser degree, fatigue, contributing only in patients with less active RA.

Chronotherapy for rheumatoid arthritis: current perspectives

Chronotherapy for rheumatoid arthritis: current perspectives Hideto To Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan Abstract: Rheumatoid arthritis (RA) is an autoimmune disorder of unknown etiology. Morning stiffness, a characteristic feature of RA, shows a 24-hour rhythm. Cytokines, which are considered to play an important role in the pathogenesis of RA, also exhibit a 24-hour rhythm, with a peak in the early morning. These rhythms have been attributed to the endogenous hormone balance and changes in expression levels of clock-related genes. Chronotherapy based on the 24-hour rhythm of RA has been performed using glucocorticoids and disease-modifying antirheumatic drugs. In a previous study, it was reported that modified-release prednisone tablets were administered to patients with RA at night, which demonstrated that the severity of morning stiffness was markedly less than that in patients receiving the standard treatment. Methotrexate (MTX) is the most frequently used RA drug worldwide. In a basic study, cytokines and inflammatory responses in RA model animals showed 24-hour rhythms, based on which MTX was administered and exerted dosing time-dependent antirheumatic effects. Plasma C-reactive protein and cytokine levels also exhibit 24-hour rhythms in patients with RA, with peaks occurring in the early morning. MTX has been shown to markedly inhibit the exacerbation of arthritis in patients with RA when it is administered as inflammatory responses and tumor necrosis factor-α levels begin to increase. Tacrolimus (TAC) is an immunosuppressive agent that is administered to patients who undergo organ transplants. Since one of the mechanisms of action of TAC is the inhibition of inflammatory cytokine production, it is used as an RA therapeutic drug. When TAC was previously administered in the early light or early dark phase to RA model animals, the group treated in the early light phase had notably inhibited increase in arthritis scores compared with that in the early dark phase. The selection of an optimal dosing time associated with 24-hour rhythms in RA symptoms may lead to more effective and safer treatments for RA using glucocorticoids and disease-modifying antirheumatic drugs. Keywords: methotrexate, steroid, circadian rhythm, cytokines