scholarly journals Median time to pain improvement and the impact of baseline pain severity on pain response in patients with psoriatic arthritis treated with tofacitinib

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001609
Author(s):  
Kurt de Vlam ◽  
Alexis Ogdie ◽  
Andrew G Bushmakin ◽  
Joseph C Cappelleri ◽  
Roy Fleischmann ◽  
...  

BackgroundPain is a core domain of psoriatic arthritis (PsA). This post hoc analysis evaluated time to pain improvement and the impact of baseline pain severity on pain response in patients with PsA receiving tofacitinib.MethodsData from two trials (NCT01877668; NCT01882439) in patients receiving tofacitinib 5 mg twice daily, placebo switching to tofacitinib 5 mg twice daily at month 3 (placebo-to-tofacitinib) or adalimumab (NCT01877668 only) were included. Improvement in pain (≥30%/≥50% decrease from baseline in Visual Analogue Scale pain score) was assessed; median time to initial (first post-baseline visit)/continued (first two consecutive post-baseline visits) pain improvement was estimated (Kaplan-Meier) for all treatment arms. A parametric model was used to determine the relationship between baseline pain severity and time to pain response in patients receiving tofacitinib.ResultsAt month 3, more patients experienced pain improvements with tofacitinib/adalimumab versus placebo. Median days (95% CI) to initial/continued pain improvements of ≥30% and ≥50%, respectively, were 55 (29–57)/60 (57–85) and 85 (57–92)/171 (90–not estimable (NE)) for tofacitinib, versus 106 (64–115)/126 (113–173) and 169 (120–189)/NE (247–NE) for placebo-to-tofacitinib. Pain improvements were also experienced more quickly for adalimumab versus placebo. Predicted time to ≥30%/≥50% pain improvement was shorter in patients with higher baseline pain versus lower baseline pain (tofacitinib arm only).ConclusionsIn patients with PsA, pain improvements were experienced by more patients, and more rapidly, with tofacitinib and adalimumab versus placebo. In those receiving tofacitinib, higher baseline pain was associated with faster pain improvements.

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jessica Ailani ◽  
J. Scott Andrews ◽  
Mallikarjuna Rettiganti ◽  
Robert A. Nicholson

Abstract Background Focus on the frequency of migraine pain may undervalue the total burden of migraine as pain duration and severity may present unique, additive burden. A composite measure of total pain burden (TPB; frequency, severity, and duration) may provide a more comprehensive characterization of pain burden and treatment response in patients with episodic migraine (EM) or chronic migraine (CM). The impact of galcanezumab versus placebo on TPB among patients with EM or CM was analyzed. Methods Patients from randomized, double-blind, placebo-controlled episodic (two 6-month studies pooled) and chronic migraine (3-month) studies received once-monthly subcutaneous injection of galcanezumab 120 mg or placebo. A post hoc analysis of TPB for a given month was calculated as severity-weighted duration by multiplying duration (hours) and maximum pain severity (0 = none, 1 = mild, 2 = moderate, 3 = severe) of migraine for each day and summing these over the days in a month. Least square mean change from baseline in monthly TPB across Months 1–6 (EM, N = 444 galcanezumab, N = 894 placebo) and Months 1–3 (CM, N = 278 galcanezumab, N = 558 placebo) were compared using a mixed-model repeated measures model. Correlation of the Migraine Specific Quality of Life Questionnaire (MSQ) and Migraine Disability Assessment Scale (MIDAS) to TPB at baseline was assessed. Results At baseline, the duration of migraine on a given migraine headache day accounted for the greatest unique proportion of variability (EM, 57.4% and CM, 61.1%) to TPB after adjusting for frequency of migraine headache days and maximum pain severity. The decrease from baseline in monthly TPB was greater with galcanezumab than placebo for patients with EM (68.6 versus 36.2) and CM (102.6 versus 44.4). The average percent reduction of TPB from baseline was significantly greater with galcanezumab compared with placebo in patients with EM (50.8% versus 17.2%) and CM (29.7% versus 11.0%). In patients with EM and CM, TPB correlated with MSQ total score (r = − 0.35 and r = − 0.37) and MIDAS (r = 0.34 and r = 0.32). Conclusions Greater reduction in TPB was seen in patients with EM and CM treated with galcanezumab 120 mg once-monthly injection relative to placebo. Discussing TPB supports patient-centric conversations regarding treatment expectations when clinicians are evaluating options for migraine prevention. Trial registration ClinicalTrials.gov: #NCT02614183 (I5Q-MC-CGAG; EVOLVE-1), #NCT02614196 (I5Q-MC-CGAH; EVOLVE-2), and #NCT02614261 (I5Q-MC-CGAI; REGAIN) – all 3 trials were registered on 23 November 2015.


RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e001067 ◽  
Author(s):  
Alen Zabotti ◽  
Dennis G McGonagle ◽  
Ivan Giovannini ◽  
Enzo Errichetti ◽  
Francesca Zuliani ◽  
...  

ObjectiveNon-specific musculoskeletal pain is common in subjects destined to develop psoriatic arthritis (PsA). We evaluated psoriatic patients with arthralgia (PsOAr) compared with psoriasis alone (PsO) and healthy controls (HCs) using ultrasonography (US) to investigate the anatomical basis for joint symptoms in PsOAr and the link between these imaging findings and subsequent PsA transition.MethodsA cross-sectional prevalence analysis of clinical and US abnormalities (including inflammatory and structural lesions) in PsOAr (n=61), PsO (n=57) and HCs (n=57) was performed, with subsequent prospective follow-up for PsA development.ResultsTenosynovitis was the only significant sonographic feature that differed between PsOAr and PsO (29.5% vs 5.3%, p<0.001), although synovitis and enthesitis were numerically more frequent in PsOAr. Five patients in PsOAr and one in PsO group developed PsA, with an incidence rate of 109.2/1000 person-years in PsOAr vs 13.4/1000 person-years in PsO (p=0.03). Visual Analogue Scale pain, Health Assessment Questionnaire, joint tenderness and US active enthesitis were baseline variables associated with PsA development.ConclusionTenosynovitis was associated with arthralgia in subjects with psoriasis. Baseline US evidence of enthesitis was associated with clinical PsA development in the longitudinal analysis. These findings are relevant for enriching for subjects at risk of imminent PsA development.


RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001486
Author(s):  
Jon T Giles ◽  
Alexis Ogdie ◽  
Juan J Gomez Reino ◽  
Philip Helliwell ◽  
Rebecca Germino ◽  
...  

ObjectivesThis post-hoc analysis explored the impact of body mass index (BMI) on tofacitinib efficacy/safety in patients with active psoriatic arthritis (PsA).MethodsData were pooled from two phase 3 studies (NCT01877668; NCT01882439). Analyses included patients randomised to tofacitinib 5/10 mg twio times a day or placebo, stratified by baseline BMI: <25 kg/m2, ≥25–<30 kg/m2, ≥30–<35 kg/m2 or ≥35 kg/m2. Endpoints (month 3): American College of Rheumatology (ACR20/50/70), Health Assessment Questionnaire-Disability Index (HAQ-DI) and Psoriasis Area and Severity Index (PASI) 75 response rates; dactylitis/enthesitis resolution rates; changes from baseline Short Form-36 Health Survey version 2 (SF-36v2) Physical/Mental Component Summary (PCS) scores and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score. Safety was also reported.ResultsAnalysis included 710 patients; 43.8% were obese (BMI ≥30 kg/m2). Tofacitinib demonstrated higher efficacy response rates at month 3, compared with placebo, regardless of baseline BMI. Generally, ACR20/50/70 and HAQ-DI response rates, enthesitis resolution rates and changes from baseline in SF-36v2 PCS score and FACIT-F total score (month 3) were reduced in patients with baseline BMI ≥35 kg/m2 versus patients with lower BMIs. Elevated alanine aminotransferase/aspartate aminotransferase levels were reported in patients with baseline BMI ≥35 kg/m2 receiving tofacitinib 5 mg but not 10 mg two times a day.ConclusionTofacitinib demonstrated greater efficacy than placebo in patients with PsA, regardless of baseline BMI. For all treatment arms, reduced efficacy was observed in patients with baseline BMI ≥35 kg/m2. Safety was generally comparable across BMI categories, although the effect of tofacitinib on liver enzymes in patients with baseline BMI ≥35 kg/m2 was inconclusive.


Author(s):  
Alexis Ogdie ◽  
Kurt de Vlam ◽  
Andrew G. Bushmakin ◽  
Joseph C. Cappelleri ◽  
Philip J. Mease ◽  
...  

Author(s):  
Elia Fernández-Martínez ◽  
María Dolores Onieva-Zafra ◽  
María Laura Parra-Fernández

(1) Background: Primary dysmenorrhea, which is characterized by menstrual pain in the absence of a pelvic pathology, is one of the main reasons for gynecological consultation. This study aimed to assess the prevalence of dysmenorrhea in a sample of university students, as well as their quality of life, and to examine the most common methods used for alleviating symptoms. (2) Methods: The participants comprised 305 female university students with a mean age of 20.32 ± 3.19 years who completed a self-report survey comprising sociodemographic, gynecological and lifestyle questions. EuroQol-5 dimensions-5 levels (EQ-5D-5L) was used to measure quality of life. (3) Results: In total, 76% of the sample suffered from dysmenorrhea. Among the students who did not suffer from dysmenorrhea, a significantly greater proportion participated in activities such as jogging or Pilates on a regular basis (several times per week). Concerning quality of life, patients with dysmenorrhea showed significant differences on the pain/discomfort scale and on the total score for perceived quality of life. However, this perception showed no correlation with the VAS (visual analogue scale) pain scale. Additionally, 90.5% of students with dysmenorrhea used pharmacological treatment, and 80% self-medicated. (4) Conclusions: Dysmenorrhea represents a major problem among youth today and the impact on the quality of life (QoL) of patients is evident. Physical activity may alleviate symptoms of dysmenorrhea and this and other complementary treatments should be promoted within health services.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hanna Abrahamsson ◽  
Sebastian Meltzer ◽  
Vidar Nyløkken Hagen ◽  
Christin Johansen ◽  
Paula A. Bousquet ◽  
...  

Abstract Background We reported previously that rectal cancer patients given curative-intent chemotherapy, radiation, and surgery for non-metastatic disease had enhanced risk of metastatic progression and death if circulating levels of 25-hydroxyvitamin D [25(OH) D] were low. Here we investigated whether the association between the vitamin D status and prognosis pertains to the general, unselected population of rectal cancer patients. Methods Serum 25(OH) D at the time of diagnosis was assessed in 129 patients, enrolled 2013–2017 and representing the entire range of rectal cancer stages, and analyzed with respect to season, sex, systemic inflammation, and survival. Results In the population-based cohort residing at latitude 60°N, 25(OH) D varied according to season in men only, who were overrepresented among the vitamin D-deficient (< 50 nmol/L) patients. Consistent with our previous findings, the individuals presenting with T4 disease had significantly reduced 25(OH) D levels. Low vitamin D was associated with systemic inflammation, albeit with distinct modes of presentation. While men with low vitamin D showed circulating markers typical for the systemic inflammatory response (e.g., elevated erythrocyte sedimentation rate), the corresponding female patients had elevated serum levels of interleukin-6 and the chemokine (C-X-C motif) ligand 7. Despite disparities in vitamin D status and the potential effects on disease attributes, significantly shortened cancer-specific survival was observed in vitamin D-deficient patients irrespective of sex. Conclusion This unselected rectal cancer cohort confirmed the interconnection of low vitamin D, more advanced disease presentation, and poor survival, and further suggested it may be conditional on disparate modes of adverse systemic inflammation in men and women. Trial registration ClinicalTrials.govNCT01816607; registration date: 22 March 2013.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Fausto Biancari ◽  
Giovanni Mariscalco ◽  
Hakeem Yusuff ◽  
Geoffrey Tsang ◽  
Suvitesh Luthra ◽  
...  

Abstract Background Acute Stanford type A aortic dissection (TAAD) is a life-threatening condition. Surgery is usually performed as a salvage procedure and is associated with significant postoperative early mortality and morbidity. Understanding the patient’s conditions and treatment strategies which are associated with these adverse events is essential for an appropriate management of acute TAAD. Methods Nineteen centers of cardiac surgery from seven European countries have collaborated to create a multicentre observational registry (ERTAAD), which will enroll consecutive patients who underwent surgery for acute TAAD from January 2005 to March 2021. Analysis of the impact of patient’s comorbidities, conditions at referral, surgical strategies and perioperative treatment on the early and late adverse events will be performed. The investigators have developed a classification of the urgency of the procedure based on the severity of preoperative hemodynamic conditions and malperfusion secondary to acute TAAD. The primary clinical outcomes will be in-hospital mortality, late mortality and reoperations on the aorta. Secondary outcomes will be stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. Discussion The analysis of this multicentre registry will allow conclusive results on the prognostic importance of critical preoperative conditions and the value of different treatment strategies to reduce the risk of early adverse events after surgery for acute TAAD. This registry is expected to provide insights into the long-term durability of different strategies of surgical repair for TAAD. Trial registration ClinicalTrials.gov Identifier: NCT04831073.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 168.2-168
Author(s):  
L. Wagner ◽  
S. Sestini ◽  
C. Brown ◽  
A. Finglas ◽  
R. Francisco ◽  
...  

Background:Inborn metabolic disorders (IMDs) currently encompass more than 1,500 diseases with new ones still to be identified1. Each of them is characterised by a genetic defect affecting a metabolic pathway. Only few of them have curative treatments, that target the respective metabolic pathway. Commonly, treatment examples include diet, substrate reduction therapies, enzyme replacement therapies, gene therapy and biologicals, enabling IMD-patient now to survive to adulthood. About 30 % of all IMDs involve the musculoskeletal system and are here referred to as rare metabolic RMDs. Generally, IMDs are very heterogenous with respect to symptoms and severity, often being systemic and affecting more children than adults. Thus, challenges include certified advanced training of adult metabolic experts, standardised transition plans, social support and development of therapies for diseases that do not have any cure yet.Objectives:Introduction of MetabERN, its structure and objectives, highlighting on the unique features and challenges of metabolic RMDs and describing the involvement of patient representation in MetabERN.Methods:MetabERN is stratified in 7 subnetworks (SNW) according to the respective metabolic pathways and 9 work packages (WP), including administration, dissemination, guidelines, virtual counselling framework, research/clinical trials, continuity of care, education and patient involvement. The patient board involves a steering committee and single point of contacts for each subnetwork and work package, respectively2. Projects include identifying the need of implementing social science to assess the psycho-socio-economic burden of IMDs, webinars on IMDs and their transition as well as surveys on the impact of COVID-193 on IMD-patients and health care providers (HCPs), social assistance for IMD-patients and analysing the transition landscape within Europe.Results:The MetabERN structure enables bundling of expertise, capacity building and knowledge transfer for faster diagnosis and better health care. Rare metabolic RMDs are present in all SNWs that require unique treatments according to their metabolic pathways. Implementation of social science to assess the psycho-socio-economic burden of IMDs is still underused. Involvement of patient representatives is essential for a holistic healthcare not only focusing on clinical care, but also on the quality of life for IMD-patients. Surveys identified unmet needs of patient care, patients having little information on national support systems and structural deficits of healthcare systems to ensure HCP can provide adequate clinical care during transition phases. These results are collected by MetabERN and forwarded to the Directorate-General for Health and Food Safety (DG SANTE) of the European Commission (EC) to be addressed further.Conclusion:MetabERN offers an infrastructure of virtual healthcare for patients with IMDs. Thus, in collaboration with ERN ReCONNET, MetabERN can assist in identifying rare metabolic disorders of RMDs to shorten the odyssey of diagnosis and advise on their respective therapies. On the other hand, MetabERN can benefit from EULAR’s longstanding experience regarding issues affecting the quality of life, all RMD patients are facing, such as pain, stiffness, fatigue, rehabilitation, maintaining work and disability claims.References:[1]IEMbase - Inborn Errors of Metabolism Knowledgebase http://www.iembase.org/ (accessed Jan 29, 2021).[2]MetabERN: European Refence Network for Hereditary Metabolic Disorders https://metab.ern-net.eu/ (accessed Jan 29, 2021).[3]Lampe, C.; Dionisi-Vici, C.; Bellettato, C. M.; Paneghetti, L.; van Lingen, C.; Bond, S.; Brown, C.; Finglas, A.; Francisco, R.; Sestini, S.; Heard, J. M.; Scarpa, M.; MetabERN collaboration group. The Impact of COVID-19 on Rare Metabolic Patients and Healthcare Providers: Results from Two MetabERN Surveys. Orphanet J. Rare Dis.2020, 15 (1), 341. https://doi.org/10.1186/s13023-020-01619-x.Acknowledgements:The authors thank the MetabERN collaboration group, the single point of contacts (SPOC) of the MetabERN patient board and the Transition Project Working Group (TPWG)Disclosure of Interests:None declared


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Arroyo-Espliguero ◽  
M.C Viana-Llamas ◽  
A Silva-Obregon ◽  
A Estrella-Alonso ◽  
C Marian-Crespo ◽  
...  

Abstract Background Malnutrition and sarcopenia are common features of frailty. Prevalence of frailty among ST-segment elevation myocardial infarction (STEMI) patients is higher in women than men. Purpose Assess gender-based differences in the impact of nutritional risk index (NRI) and frailty in one-year mortality rate among STEMI patients following primary angioplasty (PA). Methods Cohort of 321 consecutive patients (64 years [54–75]; 22.4% women) admitted to a general ICU after PA for STEMI. NRI was calculated as 1.519 × serum albumin (g/L) + 41.7 × (actual body weight [kg]/ideal weight [kg]). Vulnerable and moderate to severe NRI patients were those with Clinical Frailty Scale (CFS)≥4 and NRI&lt;97.5, respectively. We used Kaplan-Meier survival model. Results Baseline and mortality variables of 4 groups (NRI-/CFS-; NRI+/CFS-; NRI+/CFS- and NRI+/CFS+) are depicted in the Table. Prevalence of malnutrition, frailty or both were significantly greater in women (34.3%, 10% y 21.4%, respectively) than in men (28.9%, 2.8% y 6.0%, respectively; P&lt;0.001). Women had greater mortality rate (20.8% vs. 5.2%: OR 4.78, 95% CI, 2.15–10.60, P&lt;0.001), mainly from cardiogenic shock (P=0.003). Combination of malnutrition and frailty significantly decreased cumulative one-year survival in women (46.7% vs. 73.3% in men, P&lt;0.001) Conclusion Among STEMI patients undergoing PA, the prevalence of malnutrition and frailty are significantly higher in women than in men. NRI and frailty had an independent and complementary prognostic impact in women with STEMI. Kaplan-Meier and Cox survival curves Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 33.1-34 ◽  
Author(s):  
D. Simon ◽  
K. Tascilar ◽  
A. Kleyer ◽  
S. Bayat ◽  
E. Kampylafka ◽  
...  

Background:We have previously reported that the presence of musculoskeletal pain in psoriasis patients is associated with a higher risk of developing psoriatic arthritis (PsA) (1). Furthermore, a subset of psoriasis patients shows evidence for structural entheseal lesions (SEL) in their hand joints (2), sometimes also referred as “Deep Koebner Phenomenon”, which are highly specific for psoriatic disease and virtually absent in healthy controls, rheumatoid arthritis and hand osteoarthritis patients (2-4). However, it remains unclear whether SEL alone or in combination with musculoskeletal pain are associated with the development of PsA.Objectives:To test whether the presence of SEL in psoriasis patients increases the risk for progression to PsA and how this is related to the presence of musculoskeletal pain.Methods:Psoriasis patients without evidence of PsA were enrolled in a prospective cohort study between 2011 and 2018. All patients underwent baseline assessment of SEL in their 2ndand 3rdMCP joints by high-resolution peripheral quantitative computed tomography (HR-pQCT). The risk of PsA development associated with SEL and arthralgia was explored using survival analyses and multivariable Cox regression models.Results:114 psoriasis patients (72 men/42 women) with a mean (SD) follow-up duration of 28.2 (17.7) months were included, 24 of whom developed PsA (9.7 /100 patient-years, 95%CI 6.2 to 14.5) during the observation period. Patients with SEL (N=41) were at higher risk of developing PsA compared to patients without such lesions (21.4/100 patient-years, 95%CI 12.5 to 34.3, HR 5.10, 95%CI 1.53 to 16.99, p=0.008) (Kaplan Meier plot A). Furthermore, while patients without arthralgia and without SEL had a very low progression rate to PsA (1/29; 3.4%), patients with arthralgia but no SEL showed higher progression (5/33; 15.2%), which was in line with previous observations (1) (Kaplan Meier plot B). Presence of SEL further enhanced the risk for progression to PsA both in the absence (6/16; 37.5%) and presence (6/14; 42.8%) of arthralgia with the highest progression rate in those subjects with both arthralgia and SEL (p<0.001 by log rank test for trend) (Kaplan Meier plot B).Conclusion:Presence of SEL is associated with an increased risk of developing PsA in patients with psoriasis. If used together with pain, SEL allow defining subsets of psoriasis patients with very low and very high risk to develop PsA.References:[1]Faustini F et al. Ann Rheum Dis. 2016;75:2068-2074[2]Simon D et al. Ann Rheum Dis. 2016;75:660-6[3]Finzel S et al. Ann Rheum Dis. 2011;70:122-7[4]Finzel S et al. Arthritis Rheum. 2011;63:1231-6Disclosure of Interests:David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Koray Tascilar: None declared, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Sara Bayat Speakers bureau: Novartis, Eleni Kampylafka Speakers bureau: Novartis, BMS, Janssen, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Louis Schuster: None declared, Klaus Engel: None declared, Michael Sticherling Grant/research support from: Novartis, Consultant of: Advisory boards Abbvie, Celgene, Janssen Cilag, Lilly, Pfizer, MSD, Novartis, Amgen, Leo, Sanofi, UCB, Speakers bureau: Abbvie, Celgene, Janssen Cilag, Leo, MSD, Novartis, Pfizer, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB


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