Treatment with Tumor Necrosis Factor Inhibitors in Axial Spondyloarthritis: Comparison Between Private Rheumatology Practices and Academic Centers in a Large Observational Cohort

Objective.To evaluate the initiation of and response to tumor necrosis factor (TNF) inhibitors for axial spondyloarthritis (axSpA) in private rheumatology practices versus academic centers.Methods.We compared newly initiated TNF inhibition for axSpA in 363 patients enrolled in private practices with 100 patients recruited in 6 university hospitals within the Swiss Clinical Quality Management (SCQM) cohort.Results.All patients had been treated with ≥ 1 nonsteroidal antiinflammatory drug and > 70% of patients had a baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 before anti-TNF agent initiation. The proportion of patients with nonradiographic axSpA (nr-axSpA) treated with TNF inhibitors was higher in hospitals versus private practices (30.4% vs 18.7%, p = 0.02). The burden of disease as assessed by patient-reported outcomes at baseline was slightly higher in the hospital setting. Mean levels (± SD) of the Ankylosing Spondylitis Disease Activity Score were, however, virtually identical in private practices and academic centers (3.4 ± 1.0 vs 3.4 ± 0.9, p = 0.68). An Assessment of SpondyloArthritis international Society (ASAS40) response at 1 year was reached for ankylosing spondylitis in 51.7% in private practices and 52.9% in university hospitals (p = 1.0) and for nr-axSpA in 27.5% versus 25.0%, respectively (p = 1.0).Conclusion.With the exception of a lower proportion of patients with nr-axSpA newly treated with anti-TNF agents in private practices in comparison to academic centers, adherence to ASAS treatment recommendations for TNF inhibition was equally high, and similar response rates to TNF blockers were achieved in both clinical settings.

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Low BASDAI score alone is not a good predictor of anti-tumor necrosis factor treatment efficacy in ankylosing spondylitis: a retrospective cohort study

BMC Musculoskeletal Disorders ◽

10.1186/s12891-020-03941-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Bora Nam ◽

Bon San Koo ◽

Tae-Han Lee ◽

Ji-Hui Shin ◽

Jin-Ju Kim ◽

...

Keyword(s):

Cohort Study ◽

Ankylosing Spondylitis ◽

Tumor Necrosis Factor ◽

Disease Activity ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Tumor Necrosis ◽

Activity Index ◽

Rank Test ◽

Necrosis Factor

Abstract Background The purpose of this study was to determine the prevalence of high disease activity as measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS) in ankylosing spondylitis (AS) patients who nonetheless have low Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores after anti-tumor necrosis factor (TNF) treatment. Its clinical impact on anti-TNF survival was also investigated. Methods We conducted a single-centre retrospective cohort study of AS patients having low BASDAI scores (< 4) and available ASDAS-C-reactive protein (CRP) data after 3 months of first-line anti-TNF treatment. Patients were grouped into high-ASDAS (≥ 2.1) and low-ASDAS (< 2.1) groups according to the ASDAS-CRP after 3 months of anti-TNF treatment. Their characteristics were compared. And survival analyses were carried out using Kaplan–Meier curves and log-rank test with the event being discontinuation of anti-TNF treatment due to lack/loss of efficacy. Results Among 116 AS patients with low BASDAI scores after 3 months of anti-TNF treatment, 38.8% were grouped into the high-ASDAS group. The high-ASDAS group tended to have greater disease activity after 9 months of treatment (BASDAI 2.9 ± 1.1 vs. 2.3 ± 1.4, p=0.007; ASDAS-CRP 1.8 ± 0.6 vs. 1.5 ± 0.7, p=0.079; proportion of high ASDAS-CRP 27.8% vs. 13.8%, p=0.094) and greater risk of discontinuing anti-TNF treatment due to lack/loss of efficacy than the low-ASDAS group (p=0.011). Conclusions A relatively high proportion of AS patients with low BASDAI scores had high ASDAS-CRP. These low-BASDAI/high-ASDAS-CRP patients also had a greater risk for discontinuation of anti-TNF treatment due to low/lack of efficacy than the low-ASDAS group. The use of the ASDAS-CRP alone or in addition to the BASDAI may improve the assessment of AS patients treated with anti-TNF agents.

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Tumor necrosis factor-α (TNFα) inhibitors in the treatment of nonradiographic axial spondyloarthritis: current evidence and place in therapy

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x17706454 ◽

2017 ◽

Vol 9 (8) ◽

pp. 197-210 ◽

Cited By ~ 7

Author(s):

Valeria Rios Rodriguez ◽

Denis Poddubnyy

Keyword(s):

Ankylosing Spondylitis ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Axial Spondyloarthritis ◽

Efficacy And Safety ◽

Tnfα Inhibitors ◽

Factor Α ◽

Nonradiographic Axial Spondyloarthritis ◽

Necrosis Factor

Nonradiographic axial spondyloarthritis (SpA) and radiographic SpA (also known as ankylosing spondylitis) are currently considered as two stages or forms of one disease (axial SpA). The treatment with tumor necrosis factor-α (TNFα) inhibitors has been authorized for years for ankylosing spondylitis. In recent years, most of the anti-TNFα agents have also been approved for the treatment of nonradiographic axial SpA by the European Medicines Agency (EMA) and similar authorities in many countries around the world (but not in the US), increasing the number of possible therapies for this indication. Data from several clinical trials have demonstrated the good efficacy and safety profiles from those anti-TNFα agents. Presently, a large number of patients achieve a satisfactory clinical control with the current therapies, however, there remains a percentage refractory to nonsteroidal anti-inflammatory drugs (NSAIDs) and TNFα inhibitors; therefore, several new drugs are currently under investigation. In 2015, the first representative of a new class of biologics [an interleukin (IL)-17 inhibitor] secukinumab, was approved for the treatment of ankylosing spondylitis; a clinical trial in nonradiographic axial SpA is currently underway. In this review, we discuss the recent data on efficacy and safety of TNFα-inhibitors focusing on the treatment of nonradiographic axial SpA.

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Response to Tumor Necrosis Factor Inhibition in Male and Female Patients with Ankylosing Spondylitis: Data from a Swiss Cohort

The Journal of Rheumatology ◽

10.3899/jrheum.170166 ◽

2018 ◽

Vol 45 (4) ◽

pp. 506-512 ◽

Cited By ~ 11

Author(s):

Monika Hebeisen ◽

Regula Neuenschwander ◽

Almut Scherer ◽

Pascale Exer ◽

Ulrich Weber ◽

...

Keyword(s):

Sex Differences ◽

Ankylosing Spondylitis ◽

Tumor Necrosis Factor ◽

Disease Activity ◽

Tumor Necrosis ◽

Disease Status ◽

Spinal Mobility ◽

Inactive Disease ◽

Female Patients ◽

Necrosis Factor

Objective.To investigate sex differences in connection with the effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with ankylosing spondylitis (AS).Methods.A total of 440 patients with AS (294 men; 146 women) initiating a first TNFi in the prospective Swiss Clinical Quality Management Cohort were included. We evaluated the proportion of patients achieving the 20% and 40% improvement in the Assessment of Spondyloarthritis international Society criteria (ASAS20 and ASAS40) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) improvement and status scores at 1 year. Patients having discontinued TNFi were considered nonresponders. Logistic regression analyses were performed to adjust for important predictors of response.Results.Compared to men, female patients had lower mean C-reactive protein levels, better spinal mobility, and more peripheral disease at the start. There was no sex disparity with regard to the ASDAS, the Bath Ankylosing Spondylitis Disease Activity and Functional indices, and the quality of life. At 1 year, 52% of women and 63% of men achieved an ASAS20 response (OR 0.63, 95% CI 0.37–1.07, p = 0.09). An inactive disease status (ASDAS < 1.3) was reached by 18% of women and 26% of men (OR 0.65, 95% CI 0.32–1.27, p = 0.22). These sex differences in response to TNFi were more pronounced in adjusted analyses (OR 0.34, 95% CI 0.16–0.71, p = 0.005 for ASAS20 and OR 0.10, 95% CI 0.03–0.31, p < 0.001 for ASDAS < 1.3) and confirmed for all the other outcomes assessed.Conclusion.In AS, fewer women respond to TNFi and women show a reduced response in comparison to men.

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Comparative Analysis and Predictors of 10-year Tumor Necrosis Factor Inhibitors Drug Survival in Patients with Spondyloarthritis: First-year Response Predicts Longterm Drug Persistence

The Journal of Rheumatology ◽

10.3899/jrheum.170477 ◽

2018 ◽

Vol 45 (6) ◽

pp. 785-794 ◽

Cited By ~ 14

Author(s):

Irini D. Flouri ◽

Theodora E. Markatseli ◽

Kyriaki A. Boki ◽

Ioannis Papadopoulos ◽

Fotini N. Skopouli ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Tumor Necrosis Factor ◽

Disease Activity ◽

Tumor Necrosis ◽

Disease Activity Score ◽

First Year ◽

Peripheral Arthritis ◽

Drug Survival ◽

Axial Disease ◽

Necrosis Factor

Objective.To evaluate the 10-year drug survival of the first tumor necrosis factor inhibitor (TNFi) administered to patients with spondyloarthritis (SpA) overall and comparatively between SpA subsets, and to identify predictors of drug retention.Methods.Patients with SpA in the Hellenic Registry of Biologic Therapies, a prospective multicenter observational cohort, starting their first TNFi between 2004–2014 were analyzed. Kaplan-Meier curves and Cox regression models were used.Results.Overall, 404 out of 1077 patients (37.5%) discontinued treatment (followup: 4288 patient-yrs). Ten-year drug survival was 49%. In the unadjusted analyses, higher TNFi survival was observed in patients with ankylosing spondylitis (AS) compared to undifferentiated SpA and psoriatic arthritis [PsA; significant beyond the first 2.5 (p = 0.003) years and 7 years (p < 0.001), respectively], and in patients treated for isolated axial versus peripheral arthritis (p = 0.001). In all multivariable analyses, male sex was a predictor for longer TNFi survival. Use of methotrexate (MTX) was a predictor in PsA and in patients with peripheral arthritis. Absence of peripheral arthritis and use of a monoclonal antibody (as opposed to non-antibody TNFi) independently predicted longer TNFi survival in axial disease because of lower rates of inefficacy. Achievement of major responses during the first year in either axial or peripheral arthritis was the strongest predictor of longer therapy retention (HR 0.33, 95% CI 0.26–0.41 for Ankylosing Spondylitis Disease Activity Score inactive disease, and HR 0.35, 95% CI 0.24–0.50 for 28-joint Disease Activity Score remission).Conclusion.The longterm retention of the first TNFi administered to patients with SpA is high, especially for males with axial disease. The strongest predictor of longterm TNFi survival is a major response within the first year of treatment.

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Predictors of Clinical Remission under Anti-tumor Necrosis Factor Treatment in Patients with Ankylosing Spondylitis: Pooled Analysis from Large Randomized Clinical Trials

The Journal of Rheumatology ◽

10.3899/jrheum.141278 ◽

2015 ◽

Vol 42 (8) ◽

pp. 1418-1426 ◽

Cited By ~ 14

Author(s):

Xenofon Baraliakos ◽

Andrew S. Koenig ◽

Heather Jones ◽

Annette Szumski ◽

David Collier ◽

...

Keyword(s):

Clinical Trials ◽

Ankylosing Spondylitis ◽

Tumor Necrosis Factor ◽

Disease Activity ◽

Clinical Remission ◽

Partial Remission ◽

Tumor Necrosis ◽

Disease Duration ◽

Hla B27 ◽

Necrosis Factor

Objective.Investigate the role and relation of disease duration of different factors for achieving clinical remission with anti-tumor necrosis factor (TNF) treatment in patients with active ankylosing spondylitis (AS).Methods.Data pooled from 4 large (n = 1281) clinical trials were used to compare disease duration subgroups for placebo or sulfasalazine (SSZ) versus etanercept (ETN), which, in turn, were analyzed by age of diagnosis ≤ 40 versus > 40 years, HLA-B27 status, and baseline C-reactive protein (CRP) ≤ upper limit of normal (ULN) versus > ULN using chi-square tests, and ANCOVA. The primary efficacy measure was Assessments of SpondyloArthritis international Society (ASAS) partial remission (PR) after 12 weeks of treatment. Also analyzed were Bath AS Disease Activity Index and Functional Index, AS Disease Activity Scores, and ASAS response rates.Results.Overall, a larger percentage of patients achieved ASAS-PR with ETN versus SSZ or placebo. More patients with ≤ 2-year disease duration treated with ETN experienced partial remission (34%) versus longer disease duration (30%, 27%, and 22% for > 2–5, > 5–10, and > 10 yrs, respectively; all p < 0.05). In the subgroup of patients with both disease duration ≤ 2 years and aged ≤ 40 years at diagnosis, the treatment response was even more pronounced. Similar results were seen in HLA-B27–positive patients in the disease duration ≤ 2-year subgroup. Overall, patients with high CRP at baseline had better treatment responses compared with patients with normal CRP.Conclusion.Treatment response under anti-TNF treatment with ETN at 12 weeks was greatest among patients with disease duration ≤ 2 years and even more pronounced in subgroups of patients ≤ 40 years old or HLA-B27–positive at diagnosis.

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Comparison of the effects of rituximab, tumor necrosis factor alpha inhibitors and non-steroidal antiinflammatory drugs on ankylosing spondylitis clinical activity and sacroileitis intensity on magnetic resonance imaging

Kazan medical journal ◽

10.17816/kmj1809 ◽

2013 ◽

Vol 94 (6) ◽

pp. 870-876

Author(s):

M S Protopopov ◽

Sh F Erdes ◽

S A Lapshina ◽

L I Myasoutova ◽

R Kh Zakirov ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Tumor Necrosis Factor ◽

Disease Activity ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Clinical Activity ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Inflammatory Drugs ◽

Necrosis Factor

Aim. To investigate the effect of rituximab in ankylosing spondylitits on disease activity and on intensity of sacroileitis detected by magnetic resonance imagigng compared to tumor necrosis factor alpha inhibitors and non-steroidal anti-inflammatory drugs. Methods. The study included 91 patient [14 (15.4%) females, 77 (84.6%) males, mean age - 34.4±9.13 years, disease duration - 6.6±3.8 years] with established diagnosis of ankylosing spondylitits. The main group included 20 patients (17 males, mean age 36.9±9.9 years) who were treated with rituximab. The comparison group included 36 patients (30 males, mean age 34.3±8.6 years) treated with tumor necrosis factor alpha inhibitors. The control group consisted of 35 patients (30 males, mean age 33.4±9.3 years) treated with non-steroidal anti-inflammatory drugs and sulfasalazine. Disease activity was measured by BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and ASDASESR (Ankylosing Spondylitis Disease Activity Score) scores before the treatment initiation, at the 2nd, 8th, 16th and 24th weeks of treatment. Magnetic resonance imaging of sacroiliac joints was performed before the treatment initiation and at the 24th week of treatment, T1 and STIR sequences were analyzed. Results were processed using the SPARCC (Spondyloarthritis Research Consortium of Canada) scoring methodology. Results. There was a significant reduction of the disease clinical activity measured by BASDAI score (from 6.19±1.48 to 3.70±0.91, p 0.01) and ASDASESR score (form 3.43±0.72 tо 2.11±0.46, p 0.01) in patients treated with rituximab at the week 24. Mean SPARCC score reduced from 15.9±7.2 to 4.6±8.2 (p 0.01). The influence of rituximab on clinical activity of the disease was superior over the effect of the standard treatment (BASDAI and SPARCC scores 5.22±1.14 and 7.8±7.1 accordingly at the week 24, p 0.05), but inferior over the effect of tumor necrosis factor alpha inhibitors (BASDAI and SPARCC scores 2.03±0.64 и 4.9±7.0 accordingly at the week 24, p 0.01). Conclusion. Anti B-cell therapy is effective in treating active ankylosing spondylitis and leads to the decrease of the clinical symptoms intensity and disease activity measured by BASDAI и ASDASESR scores. The effect of rituximab was superior over the effect of non-steroidal anti-inflammatory drugs and sulfasalazine and inferior over the effect of tumor necrosis factor alpha inhibitors.

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New Onset, Aggravation and Recurrence of Crohn's Disease upon Treatment with Three Different Tumor Necrosis Factor Inhibitors

Case Reports in Gastroenterology ◽

10.1159/000381637 ◽

2015 ◽

Vol 9 (1) ◽

pp. 106-112 ◽

Cited By ~ 5

Author(s):

Jonas Zeitz ◽

Susann Enderlin ◽

Luc Biedermann ◽

Matthias Turina ◽

Sebastian Leibl ◽

...

Keyword(s):

Crohn’S Disease ◽

Tumor Necrosis Factor ◽

Crohn's Disease ◽

Tumor Necrosis ◽

Tnf Inhibitors ◽

Etanercept Treatment ◽

Abdominal Symptoms ◽

Long Term Treatment ◽

Tnf Inhibition ◽

Necrosis Factor

Tumor necrosis factor (TNF) is a major cytokine in the pathogenesis of inflammatory bowel disease (IBD), and TNF inhibition is a cornerstone of contemporary IBD therapy. However, paradoxical induction of IBD has recently been reported upon treatment of rheumatologic disorders with TNF inhibitors. In previous cases, induction of IBD was associated with one single drug and IBD was successfully managed by switching TNF inhibitors. We report the case of a patient with juvenile rheumatoid arthritis under long-term treatment with etanercept. After switching TNF inhibition to adalimumab, symptoms of Crohn's disease (CD) occurred and the diagnosis of CD was established by endoscopy. Further treatment with adalimumab and subsequently infliximab aggravated the abdominal symptoms, necessitating ileocecal resection, after which symptoms resolved for several months. Etanercept treatment due to recurrent rheumatologic symptoms was followed by recurrent CD symptoms and findings, which resolved upon discontinuation of etanercept. This case suggests that induction, aggravation and recurrence of IBD can be rare class effects of TNF inhibition.

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Tumor Necrosis Factor-α Inhibition in Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis: Treatment Response, Drug Survival, and Patient Outcome

The Journal of Rheumatology ◽

10.3899/jrheum.150372 ◽

2015 ◽

Vol 42 (12) ◽

pp. 2376-2382 ◽

Cited By ~ 11

Author(s):

Justine Corli ◽

René-Marc Flipo ◽

Peggy Philippe ◽

Anne Bera-Louville ◽

Hélène Béhal ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Axial Spondyloarthritis ◽

Drug Survival ◽

Baseline Characteristics ◽

Factor Α ◽

Nonradiographic Axial Spondyloarthritis ◽

Necrosis Factor

Objective.The purpose of this study was to (1) evaluate baseline characteristics of nonradiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) treated with tumor necrosis factor-α inhibitors (TNFi), (2) assess the response to first TNFi treatment, and (3) compare drug-survival duration and rates.Methods.Inclusion criteria were patients with axSpA who initiated first TNFi treatment between April 2001 and July 2014 and were followed up for at least 3 months. Efficacy criteria were an improvement of at least 2 points (on a 0–10 scale) or a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Baseline characteristics, responses at 12 months, and drug survival were compared between AS and nr-axSpA.Results.A total of 361 patients were included in the study (AS, n = 263 and nr-axSpA, n = 98). Patients with AS were more often men (65.02% vs 45.92%, p = 0.001) and had longer symptom duration (11.71 ± 9.52 vs 7.34 ± 9.30 yrs, p < 0.001). Median levels of acute-phase reactants (C-reactive protein and erythrocyte sedimentation rate) were significantly higher in patients with AS (p < 0.001 for both). Median BASDAI scores at first TNFi initiation were not higher in patients with nr-axSpA than in patients with AS (59, 49–70 vs 60, 50–70, p = 0.73). BASDAI 20 and BASDAI 50 response rates at 12 months were not statistically different between patients with AS and patients with nr-axSpA (74.58% vs 64.58%, p = 0.19 and 61.02% vs 50.00%, p = 0.19, respectively). No statistically significant difference in terms of survival was observed between patients with AS and nr-axSpA (p = 1.00).Conclusion.Treatment response and drug survival were similar in patients with AS and nr-axSpA after first TNFi initiation.

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Remission in Nonradiographic Axial Spondyloarthritis Treated with Anti-tumor Necrosis Factor-α Drugs: An Italian Multicenter Study

The Journal of Rheumatology ◽

10.3899/jrheum.140811 ◽

2014 ◽

Vol 42 (2) ◽

pp. 258-263 ◽

Cited By ~ 24

Author(s):

Ennio Lubrano ◽

Fabio Massimo Perrotta ◽

Antonio Marchesoni ◽

Salvatore D’Angelo ◽

Roberta Ramonda ◽

...

Keyword(s):

New York ◽

Clinical Practice ◽

Ankylosing Spondylitis ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Axial Spondyloarthritis ◽

Rank Test ◽

Tnf Α ◽

Nonradiographic Axial Spondyloarthritis ◽

Necrosis Factor

Objective.To investigate the possibility of achieving partial remission (PR) in patients with nonradiographic axial spondyloarthritis (nr-axSpA) versus ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (TNF)-α antagonists, such as adalimumab (ADA), etanercept (ETN), and infliximab (IFX), in a real clinical practice setting. The Assessment of SpondyloArthritis international Society (ASAS) 20, ASAS40, and Ankylosing Spondylitis Disease Activity Score were also calculated.Methods.A retrospective study was conducted in patients with axSpA treated with ADA, ETN, and IFX from 2000 to 2013. All patients fulfilled the ASAS or the modified New York criteria. PR was reached when the score was < 20 mm (on a visual analog scale of 0–100 mm) in each of these domains: (1) patient global assessment, (2) pain, (3) function, and (4) inflammation.Results.A total of 321 patients with axSpA were treated. Among them, 62 were nr-axSpA while the remaining 259 were AS. Log-rank test to compare survival curves showed that the probability of obtaining PR in nr-axSpA and AS during treatment with anti-TNF-α was not significantly different. At 12 weeks of exposure to the first anti-TNF-α drug, PR was achieved in 7 patients with nr-axSpA (11.3%) and in 68 patients with AS (26.2%).Conclusion.Our results, obtained from clinical practice, showed that PR is an achievable target of anti-TNF-α treatment in nr-axSpA. The PR rate, as a reliable indicator of sustained effectiveness, is similar in nr-axSpA and in AS.

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