scholarly journals Treatment strategies in axial spondyloarthritis: what, when and how?

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_4) ◽  
pp. iv79-iv89
Author(s):  
George E Fragoulis ◽  
Stefan Siebert
Keyword(s):  
Radiographic Progression ◽  
Axial Spondyloarthritis ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Pharmacological Interventions ◽  
Symptomatic Management ◽  
Proven Efficacy ◽  
Line Drug ◽  
Optimal Treatment Strategy

Abstract There have been major advances in the management of axial spondyloarthritis (axSpA) with the introduction of effective biologic agents targeting TNF and IL-17A. Clinicians now have more choice but, despite treatment recommendations, are still faced with significant uncertainty when deciding on the optimal treatment strategy for an individual patient in clinical practice. Management of axSpA typically requires both non-pharmacological and pharmacological interventions. NSAIDs remain the first line drug therapies for axSpA with proven efficacy for symptomatic management but uncertainty remains regarding their optimal long-term use relating to radiographic progression and safety in axSpA. To-date there are no head-to-head trials of biologics in axSpA. Clinicians need to consider other factors, including extra-articular manifestations, comorbidities, safety and radiographic progression when deciding on which biologic to recommend for an individual patient. This article will explore the evidence relating to these factors and highlight areas of unmet need.

Effect of biologic disease-modifying anti-rheumatic drugs targeting remission in axial spondyloarthritis: systematic review and meta-analysis

Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3158-3171
Author(s):  
Ana Rita Cruz-Machado ◽  
Santiago Rodrigues-Manica ◽  
Joana Leite Silva ◽  
Irina Alho ◽  
Constança Coelho ◽  
...  
Keyword(s):  
Disease Activity Score ◽  
Axial Spondyloarthritis ◽  
Meta Analysis ◽  
Unmet Need ◽  
Inactive Disease ◽  
Biologic Dmards ◽  
Randomized Controlled ◽  
Secondary Endpoints ◽  
Study Designs

Abstract Objectives To assess the efficacy of biologic DMARDs (bDMARDs) in achieving Assessment of Spondyloarthritis International Society partial remission (ASAS-PR) and/or Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS-ID), as remission-like surrogates, in axial SpA (axSpA). Methods Data from randomized controlled trials (RCTs), including long-term extensions, were included. A systematic literature review was performed using the MEDLINE database (first search May 2018, updated February 2020) and PICO criteria according to Patients—adults with radiographic or non-radiographic axSpA; Intervention—any bDMARD; Comparator—placebo and/or any different drug; Outcomes—ASAS-PR and/or ASDAS-ID as primary or secondary endpoints. Meta-analysis was performed after assessment of the homogeneity of study designs, populations and outcomes. Results After screening 155 references, a total of 22 RCTs and 28 long-term extensions were retrieved. ASAS-PR was the dominant remission-like definition used. Concerning TNF inhibitors, 14/17 RCTs provided evidence of efficacy in reaching remission at different time points: 12, 16, 24 and 28 weeks (ASAS-PR in 16–62% of patients and ASDAS-ID in 24–40% of patients). With a limited number of studies available, IL-17A inhibitors exhibited remission rates of 15–21% for ASAS-PR and 11–16% for ASDAS-ID at week 16. A meta-analysis regarding ASAS-PR was performed considering RCTs with a similar duration (12, 16 or 24 weeks). The relative risk for achieving remission was 3.864 (95% CI 2.937, 5.085). Conclusion bDMARDs have a clear impact in axSpA remission evaluated by ASAS-PR. Nevertheless, these data show an unmet need for improved reporting of remission-like outcomes.

Progression of acromegalic arthropathy in long-term controlled acromegaly patients: 9 years of longitudinal follow-up

2020 ◽  
Vol 106 (1) ◽  
pp. 188-200
Author(s):  
Iris C M Pelsma ◽  
Nienke R Biermasz ◽  
Wouter R van Furth ◽  
Alberto M Pereira ◽  
Herman M Kroon ◽  
...  
Keyword(s):  
Radiographic Progression ◽  
Treatment Strategies ◽  
Multivariable Model ◽  
Smallest Detectable Change ◽  
Kellgren And Lawrence ◽  
And Function ◽  
Prospective Longitudinal ◽  
Acromegalic Arthropathy

Abstract Context Joint complaints in patients with acromegaly are common, although the long-term disease course is largely unknown. Objective This study aims to evaluate the long-term course of acromegalic arthropathy. Design and Setting A prospective longitudinal cohort study was conducted in controlled acromegaly patients followed at a tertial referral center, with 3 study visits: at baseline and after a median of 2.6 and 9.1 years. Patients We included 31 patients with biochemically controlled acromegaly for 2 or more years (49% female; median age, 60 years) at baseline. Main Outcome Measures Radiographic arthropathy of the knee, hip, hand, and cervical and lumbar spine were evaluated using Kellgren and Lawrence (KL) scores, developed for assessment of primary osteoarthritis (OA). Radiographic progression was defined as a KL increase above the smallest detectable change. Joint symptoms were assessed using self-reported questionnaires. Progression was defined using existing clinically important cutoff values. Risk factors for progression were investigated using a multivariable model. Results All patients had definite radiographic OA at 1 or more joints at baseline. Radiographic progression was observed in 29%, 48%, 84%, and 94% of patients in the knees, hips, hands, and axial joints, respectively. Deterioration in hand-related pain and function was observed in 10 (32.3%) and 11 patients (35.5%), respectively. Solely baseline KL scores of the hip were associated with hip OA progression (OR 1.88; 95% CI, 1.09-3.16). Conclusions Acromegalic arthropathy showed significant radiographic progression over 9.1 years of follow-up in patients in remission, whereas clinical progression was observed less frequently. Future studies should focus on adequate prevention and treatment strategies of acromegalic arthropathy.

AB0700 RADIOGRAPHIC PROGRESSION IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS UNDER TREATMENT WITH TNF INHIBITORS. DATA FROM REGISPONSERBIO (SPANISH REGISTER OF BIOLOGICAL THERAPY IN SPONDYLOARTHRITIDES)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1646-1646
Author(s):  
M. Llop Vilaltella ◽  
M. Moreno ◽  
J. Gratacos-Masmitja ◽  
V. Navarro-Compán ◽  
E. De Miguel ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Structural Damage ◽  
Radiographic Progression ◽  
Biological Therapy ◽  
Axial Spondyloarthritis ◽  
Change Score ◽  
Tnf Inhibitors ◽  
Research Support

Background:Clinical efficacy of TNF inhibitors (TNFi) in axial spondyloarthritis (axSpA) has been widely probed in randomized control trials. In clinical practice, some studies suggested that long-term (more than 4 years) treatment with TNFi could slow down radiographic progression in axSpA; however, whether this treatment inhibits structural damage remains unclear.Objectives:To evaluate radiographic progression in axSpA patients receiving long-term TNFi (over 4 years) in comparison with patients starting TNFi.Methods:A total of 204 patients with axSpA were included in the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO). Out of these, 80 patients (31 starting TNFi and 49 under long-term TNFi) were included in this study based on the availability of spinal radiographs (cervical and lumbar lateral views), at two time points. Radiographs in patients starting TNFi were available: i) at baseline (before TNFi) and ii) after 3 to 5 years of TNFi therapy (mean follow-up 3.7±0.8), while in long-term TNFi patients, these were available: i) at one follow-up visit at least 4 years later since TNFi was started and ii) after 3 to 5 years of this visit (mean follow-up 3.5±1.1). Two trained readers, not blinded for chronological order, independently scored lateral cervical and lumbar spine images according to the mSASSS system (0-72). Following definitions for progression were used: change of the absolute scores, change of ≥2 units, development of new syndesmophytes, and development of new syndesmophytes or growth of the existing syndesmophytes.Results:Reliability of both readers was excellent with intraclass correlation coefficients (ICCs) of 0.98 (0.98-0.99) at inclusion and 0.98 (0.97-0.99) at follow-up. Most patients (82.5%) were classified as radiographic axSpA. Mean BASDAI at first visit (i) was of 5.0±2.4 for starting TNFi patients and of 3.2±1.9 for long-term TNFi patients. The table depicted the results for radiographic scores and progression. Mean mSASSS score at first visit (i) was 15.8±21.5 and 15.1±18.4 units for starting TNFi and long-term TNFi patients, respectively. The change score between both visits was 2.3±4.2 and 2.3±4.1, respectively. Similarly, no differences were found for change of ≥2 points (32.3% in starting TNFi and 35% in long-term TNFi patients). However, development of new syndesmophytes or growth of the existing syndesmophytes were found to be more frequently (but not significant) in starting TNFi patients compare to long-term TNFi patients.Conclusion:In patients with axSpA treated with TNFi in clinical practice radiographic progression is observed, independently of the time under this therapy. Nevertheless, the development and growth of syndesmophytes seem to be lower in long-term treated patients.Table.Starting TNFi patientsLong-term TNFi patients*p-valuePresence of syndesmophytes at first visit, % (n)45.2% (14)53.1% (26)NSPresence of syndesmophytes at follow up, %51.6% (16)55.1% (27)NSMean change score, mean ± SD2.32 ± 4.192.26 ± 4.09NSChange of ≥ 2 units in the score % (n)32.3% (10)34.7% (17)NSDevelopment of new syndesmophytes, % (n)29% (9)18.4% (9)0.3Progression or development of new syndesmopyhtes % (n)29% (9)22.4% (11)0.5* Patients with more than 4 years under TNFi treatmentDisclosure of Interests:María LLop Vilaltella Speakers bureau: Janssen and Pfizer, Mireia Moreno: None declared, Jordi Gratacos-Masmitja Grant/research support from: a grant from Pfizzer to study implementation of multidisciplinary units to manage PSA in SPAIN, Consultant of: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Speakers bureau: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Victoria Navarro-Compán Consultant of: Abbvie, Lilly, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Lilly, Novartis, Pfizer, UCB, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Font Ugalde Pilar: None declared, Teresa Clavaguera Speakers bureau: novartis, BMS, Faes, Luis F. Linares Ferrando: None declared, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Xavier Juanola-Roura: None declared

Spinal Radiographic Progression and Predictors of Progression in Patients With Radiographic Axial Spondyloarthritis Receiving Ixekizumab Over 2 Years

2021 ◽  
pp. jrheum.210471
Author(s):  
Désirée van der Heijde ◽  
Mikkel Østergaard ◽  
John D. Reveille ◽  
Xenofon Baraliakos ◽  
Andris Kronbergs ◽  
...  
Keyword(s):  
Radiographic Progression ◽  
Axial Spondyloarthritis ◽  
Hla B27 ◽  
Link Type ◽  
Long Term Effect ◽  
Structural Progression ◽  
Measuring Change ◽  
Treatment Predictors ◽  
Radiographic Changes

Objective To evaluate the long-term effect of ixekizumab on radiographic changes in the spine in patients with radiographic axial spondyloarthritis (r-axSpA) by measuring change from baseline through 2 years in modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and to identify potential predictors of progression. Methods This study evaluates patients from COAST-V (NCT02696785, bDMARD-naive) and COAST-W (NCT02696798, TNFi-experienced) who had mSASSS data at baseline in the originating studies and 108 weeks after baseline in the extension study COAST-Y (NCT03129100). We examined the proportion of patients who did not have spinal radiographic progression through 2 years (108 weeks) of treatment with ixekizumab (80 mg every 2 or 4 weeks) and the change from baseline to year 2 in mSASSS. Potential predictors of spinal radiographic progression were also evaluated. Results Among patients with evaluable radiographs who were originally assigned to ixekizumab (N=230), mean (SD) change in mSASSS from baseline at year 2 was 0.3 (1.8). The proportion of non-progressors over 2 years was 89.6% if defined as mSASSS change from baseline <2 and 75.7% if defined as mSASSS change from baseline ≤0. Predictors of structural progression at year 2 (mSASSS change >0) were age ≥40, baseline syndesmophytes, HLA-B27 positivity and male gender. Week 52 inflammation in SPARCC spine was also a predictor of radiographic progression at year 2 in patients with MRI-data in COAST-V (N=109). Conclusion The majority of patients with r-axSpA receiving ixekizumab had no radiographic progression in the spine through 2 years of treatment. Predictors were generally consistent with previous studies.

scholarly journals The Difficult-to-Treat del 17 p Patient—A Case Report in Chronic Lymphocytic Leukemia

Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 33
Author(s):  
Ana-Maria Moldovianu ◽  
Ana Manuela Crisan ◽  
Zsofia Varady ◽  
Daniel Coriu
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Lymphocytic Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Risk Patients ◽  
Potential Benefits

Chronic lymphocytic leukemia (CLL) treatment strategies have evolved to include mechanism-driven drugs but now raise new questions regarding their optimum timing and sequencing. In high-risk patients, switching from pathway inhibitors to allogeneic stem cell transplantation (allo-HCT) is still a matter of intense debate. We report the case of a CLL patient with 17 p deletion treated with ibrutinib as a bridge to allo-HCT. Early relapse after allo-HCT urged the initiation of salvage therapy, including donor lymphocytes infusions, ibrutinib, and venetoclax. We aim to outline and discuss the potential benefits of novel therapies, the current role of allo-HCT in CLL, drug timing and sequencing, and the unmet need to improve the long-term outcome of high-risk CLL patients.

Non-pharmacological management in axial spondyloarthritis

2016 ◽  
Author(s):  
Laura Passalent ◽  
Salih Ozgocmen
Keyword(s):  
Ankylosing Spondylitis ◽  
Muscle Strength ◽  
Social Participation ◽  
Axial Spondyloarthritis ◽  
Treatment Strategies ◽  
Treatment Modalities ◽  
Pharmacological Interventions ◽  
Pharmacological Management ◽  
Joint Contractures ◽  
Improve Muscle Strength

The ASAS/EULAR panel recommends a multidisciplinary and patient-centred approach that includes a combination of pharmacological and non-pharmacological treatment modalities. These updated recommendations describe a number of non-pharmacological interventions as the cornerstone of treatment in patients with ankylosing spondylitis (AS). The aims of such treatment are to: (1) reduce pain and discomfort; (2) maintain or improve muscle strength, endurance, flexibility, mobility, balance, physical fitness, and social participation; and (3) prevent spinal abnormalities, joint contractures, and deformities. This chapter presents the evidence in support of common non-pharmacological interventions for axial spondyloarthritis (axSpA) and provides recommendations regarding the implementation of such treatment strategies.

scholarly journals Recent advances in managing axial spondyloarthritis

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 697
Author(s):  
Priyanka Agrawal ◽  
Pedro M. Machado
Keyword(s):  
Radiographic Progression ◽  
Axial Spondyloarthritis ◽  
Axial Skeleton ◽  
Treatment Modalities ◽  
Current Evidence ◽  
Treat To Target ◽  
First Line ◽  
Biologic Drugs ◽  
Inflammatory Drugs ◽  
Line Drug

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease that predominantly affects the axial skeleton. The advent of biologic drugs has transformed the management of patients with axSpA. However, non-steroidal anti-inflammatory drugs remain the first-line drug treatment for axSpA. The optimal management of patients with axSpA requires a combination of pharmacological and non-pharmacological treatment modalities, namely exercise and physical therapy. This review looks at novel therapeutic options in patients with axSpA. It also summarises current evidence regarding radiographic progression and treat-to-target in axSpA.

scholarly journals Sustained Low Disease Activity Measured By ASDAS Slow Radiographic Spinal Progression in Axial Spondyloarthritis Patients Treated With TNF-inhibitors. Data from REGISPONSERBIO

2021 ◽  
Author(s):  
Maria Llop ◽  
Mireia Moreno ◽  
Victoria Navarro-Compán ◽  
Xavier Juanola ◽  
Eugenio de Miguel ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Radiographic Progression ◽  
Axial Spondyloarthritis ◽  
Term Treatment ◽  
Tnf Inhibitors ◽  
Low Disease Activity ◽  
Long Term Treatment

Abstract Background: To evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi).Methods: The study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: i) long-term treatment (≥4 years) and ii) no long-term treatment (< 4 years). Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. Disease activity differences between patients’ groups at each time point were assessed using a linear mixed-effect model.Results: Radiographic progression was defined as an increase in ≥2 mSASSS units. At inclusion, approximately half of the patients (45.5%) were receiving long-term treatment with TNFi (≥4 years). In this group of subjects, a significant difference in averaged Ankylosing Spondylitis disease Activity Score (ASDAS) across follow-up was found between progressors and non-progressors (2.33 vs 1.76, p=0.027, respectively). In patients not under long-term TNFi treatment (54.5%) though, no significant ASDAS differences were observed between progressors and non-progressors until the third year of follow-up. Furthermore, no significant differences were found in progression status, when disease activity was measured by Bath Ankylosing spondylitis Disease Activity Index (BASDAI) and C reactive protein (CRP).Conclusions: Patients on long-term TNFi treatment with a mean sustained low disease activity measures by ASDAS presented lower radiographic progression than those with active disease.

Multidisciplinary Evidence to Treat Bilingual Individuals with Aphasia

2008 ◽  
Vol 15 (3) ◽  
pp. 66-72 ◽  
Author(s):  
José G. Centeno
Keyword(s):  
Stroke Rehabilitation ◽  
Culturally Diverse ◽  
Treatment Strategies ◽  
The United States ◽  
Intervention Strategies ◽  
Steady Increase ◽  
Clinical Procedures ◽  
Bilingual Speakers ◽  
Aphasic Clients

Abstract The steady increase in linguistic and cultural diversity in the country, including the number of bilingual speakers, has been predicted to continue. Minorities are expected to be the majority by 2042. Strokes, the third leading cause of death and the leading cause of long-term disability in the U.S., are quite prevalent in racial and ethnic minorities, so population estimates underscore the imperative need to develop valid clinical procedures to serve the predicted increase in linguistically and culturally diverse bilingual adults with aphasia in post-stroke rehabilitation. Bilingualism is a complex phenomenon that interconnects culture, cognition, and language; thus, as aphasia is a social phenomenon, treatment of bilingual aphasic persons would benefit from conceptual frameworks that exploit the culture-cognition-language interaction in ways that maximize both linguistic and communicative improvement leading to social re-adaptation. This paper discusses a multidisciplinary evidence-based approach to develop ecologically-valid treatment strategies for bilingual aphasic individuals. Content aims to spark practitioners' interest to explore conceptually broad intervention strategies beyond strictly linguistic domains that would facilitate linguistic gains, communicative interactions, and social functioning. This paper largely emphasizes Spanish-English individuals in the United States. Practitioners, however, are advised to adapt the proposed principles to the unique backgrounds of other bilingual aphasic clients.

NF-κB as a Key Mediator of Brain Inflammation in Alzheimer’s Disease

2019 ◽  
Vol 18 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Chul Ju Hwang ◽  
Dong-Young Choi ◽  
Mi Hee Park ◽  
Jin Tae Hong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Strategies ◽  
Close Correlation ◽  
Specific Protein ◽  
Brain Inflammation ◽  
Cytokines And Chemokines ◽  
Inflammatory Drugs ◽  
Peptide Fibrils

Alzheimer’s disease is the most common form of dementia. It is characterized by betaamyloid peptide fibrils which are extracellular deposition of a specific protein, accompanied by extensive neuroinflammation. Various studies show the presence of a number of inflammation markers in the AD brain: elevated inflammatory cytokines and chemokines, and an accumulation of activated microglia in the damaged regions. NF-κB is a family of redox sensitive transcriptional factors, and it is known that NF-κB has binding sites in the promoter region of the genes involved in amyloidogenesis and inflammation. Long-term use of non-steroidal anti-inflammatory drugs prevents progression of AD and delays its onset, suggesting that there is a close correlation between NF-κB and AD pathogenesis. This study aims to (1) assess the association between NF-κB activity and AD through discussion of a variety of experimental and clinical studies on AD and (2) review treatment strategies designed to treat or prevent AD with NF-κB inhibitors.

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