scholarly journals The effect of tumour necrosis factor inhibitors on radiographic progression in axial spondyloarthritis: a systematic literature review

Rheumatology ◽  
2019 ◽  
Vol 58 (11) ◽  
pp. 1907-1922 ◽  
Author(s):  
Nadine Boers ◽  
Celia A J Michielsens ◽  
Désirée van der Heijde ◽  
Alfons A den Broeder ◽  
Paco M J Welsing
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Radiographic Progression ◽  
Axial Spondyloarthritis ◽  
Standard Dose ◽  
Tnf Α ◽  
Significant Difference ◽  
Synthetic Dmards ◽  
Necrosis Factor

Abstract The effect of TNF-α inhibitors (TNFi), with or without concomitant NSAIDs, on radiographic progression in axial SpA remains unclear. Therefore, we performed a systematic literature review up to January 2019 to determine whether longer use of standard dose TNFi is superior vs lower duration or lower dose TNFi therapy, conventional synthetic DMARDs alone, or no therapy in inhibiting radiographic progression in patients with axial SpA. Our search yielded 373 titles of which 14 full text articles and five abstracts were eligible for quantitative analysis. Studies had an overall moderate to critical risk of bias. Data could not be pooled due to clinical and methodological heterogeneity. Individual studies showed conflicting results with mainly no significant difference in radiographic progression when comparing effect of TNFi therapy to no TNFi therapy or when comparing to less TNFi therapy until 2 years of follow-up. Results that are more significant are shown after 2 years’ follow-up, mainly in subgroups with baseline syndesmophytes. Data on the additional or synergistic effect of concomitant NSAID use were inconclusive.

scholarly journals AB0637 EFFICACY OF COMEDICATION OF CONVENTIONAL SYNTHETIC DMARDS WITH TNF BLOCKERS IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1613.3-1614
Author(s):  
K. Ben Abdelghani ◽  
Y. Gzam ◽  
A. Fazaa ◽  
S. Miladi ◽  
K. Ouenniche ◽  
...  
Keyword(s):  
Partial Remission ◽  
Axial Spondyloarthritis ◽  
Combined Therapy ◽  
Response To Treatment ◽  
Tnf Alpha ◽  
Disease Modifying Antirheumatic Drugs ◽  
Significant Difference ◽  
Synthetic Dmards ◽  
The Mean ◽  
Necrosis Factor

Background:Tumour necrosis factor blockers (anti-TNFs) are typically used in axial spondyloarthritis (ax-SpA) when the disease has not responded adequately to conventional therapy. However, the effects of the comedication conventional synthetic disease modifying antirheumatic drugs (csDMARDs) with anti-TNFs are inconclusive.Objectives:The aim of this study was to evaluate the efficacy of comedication csDMARD and anti-TNF compared with anti-TNFs on monotherapy.Methods:A descriptive retrospective study including 85 patients with ax-SpA according to the criteria of the group ASAS on 2009 and having received anti-TNFs between January 2000 and October 2019.The patients were divided on two groups, those who had received combined therapy with cs-DMARDs and those who had received anti-TNFs on monotherapy.The response to treatment was assessed with the ASAS 40 response and partial remission at 3 and 6 months of treatment and was compared between the two groups.Results:Our populations consists of 67 men and 18 women with a mean age of 44,4 ± 10,9 years. The mean period of evolution was 12,3 ± 9,1 years and 52,2% of patients were HLA-B27 positive. The ax-SpA was associated with peripheral arthritis, enthesitis and dactylitis in 17,6%, 17,6% and 1,2% respectively.Fifty-nine patients (69,4%) were treated with anti-TNF alpha on monotherapy and 26 patients (30,6%) had combined therapy. The ASAS 40 response was achieved in 45,6% of patients at 3 months and 64,1 % of them at 6 months of anti-TNFs treatment. Among them, 7,4% had obtained partial remission at 3 months and 20,3% at 6 months of treatment.There was statically significant difference between the two groups on the ASAS 40 response or the partial remission at 3 and 6 months of treatments.Conclusion:The comedication therapy with csDMARDs does not influence the efficacy of anti-TNFs in ax-SpA patients suggesting no benefit in the concomitant use of these drugs in clinical practice.References:[1]Simone Det al. J Rheumatol Suppl. 2015;93:65–9.Disclosure of Interests:None declared

scholarly journals POS0204 AUTOANTIBODIES AND SYSTEMIC LUPUS ERYTHEMATOSUS INDUCED BY ANTI-TUMOUR NECROSIS FACTOR ALPHA THERAPY IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 318.1-318
Author(s):  
D. Santos Oliveira ◽  
A. Martins ◽  
F. R. Martins ◽  
F. Oliveira Pinheiro ◽  
M. Rato ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Disease Duration ◽  
Seroconversion Rate ◽  
Necrosis Factor Alpha ◽  
Malar Rash ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Over Time

Background:Anti-tumour necrosis factor alpha (anti-TNF-α) therapy is commonly used to treat inflammatory conditions such as rheumatoid arthritis (RA). Autoantibodies namely antinuclear antibodies (ANA) induced by these treatments are well established. However, anti-TNF-α-induced systemic lupus erythematosus (SLE) is rarely described and its incidence is yet unknown.Objectives:This study aimed to determine the prevalence of ANA seroconversion and to characterize the development of SLE induced by anti-TNF-α therapy in patients with RA over time.Methods:An observational retrospective cohort study was conducted with at least one year of follow-up. Patients with diagnosis of RA, according to American College of Rheumatology criteria (ACR), and registered on Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2003 and 2019 were included. Patients with positive ANA (titer ≥100) and/or positive double-strand DNA (dsDNA) antibodies and/or with a diagnosis of SLE at their first visit were excluded. Demographic, clinical and laboratory data were obtained by consulting Reuma.pt. As there are no recognized criteria for drug-induced SLE, the diagnosis of SLE induced by anti-TNF-α was considered if there is a temporal relationship between clinical manifestations and anti-TNF-α-therapy, the presence of at least 1 serologic ACR criteria (ANA or anti-dsDNA) and at least 1 nonserologic ACR criteria (arthritis, serositis, hematologic disorder or malar rash) [1]. Continuous variables are presented with mean, standard deviation, median, quartile 1 and quartile 3. Categorical variables are presented with absolute and relative frequencies.Results:A total of 211 patients (mean age of 49.9±10.9 years old; 84.4% female) were included with a median follow-up time of 6 [3-14] years. We found a seroconversion rate for ANA of 75.4% (n=159) with median treatment duration of 31 [8.5-70.5] months. The most common titre was 1/100 with diffuse and speckled patterns. ANA seroconversion was higher for etanercept (47.8%, n=76) than with adalimumab (23.9%, n=38), infliximab (13.8%, n=22), golimumab (12.6%, n=20) or certolizumab (1.9%, n=3). SLE induced by anti-TNF-α occurred in two patients (0.9%) with erosive and seropositive (rheumatoid factor and anti-citrullinated protein antibodies) RA previously treated with two conventional synthetic disease-modifying antirheumatic drugs, including methotrexate. The first patient, a female with 66 years old and 17 years of disease duration, developed SLE after 16 months of infliximab, with constitutional symptoms, abrupt worsening of polyarthritis, ANA titer of 1/320 diffuse pattern and positive dsDNA (248 UI/mL) antibodies. The second patient, a woman with 43 years old and 11 years of disease duration, developed SLE after 41 months of adalimumab with malar rash and ANA titer of 1/320 diffuse pattern, positive dsDNA (285 UI/mL), positive anti-histone antibodies and hypocomplementemia. In these two cases, anti-TNF-α therapy was stopped and recovery was spontaneous without treatment. The first patient switched to adalimumab and the second switched to golimumab without recurrence of SLE for more than ten years.Conclusion:We found a high rate of ANA seroconversion induced by anti-TNFα therapy in patients with RA. However, similar to previous literature, only 0.9% of patients developed SLE with mild manifestations without major organ involvement. Although the drug with the highest ANA seroconversion rate was etanercept, those responsible for induced SLE were infliximab and adalimumab. Patients improved after discontinuation of therapy and tolerated an alternative anti-TNF-α drug without recurrence of induced SLE over time. Therefore, ANA and SLE induced by anti-TNF-α should be considered and reported in the follow-up of RA patients. Further research is needed to explore the impact of this adverse event on the outcomes of treatment over time.References:[1]Hochberg MC. Arthritis Rheum. 1997;40(9):1725.Disclosure of Interests:None declared

scholarly journals Association of biological antirheumatic therapy with risk for type 2 diabetes: a retrospective cohort study in incident rheumatoid arthritis

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e042246
Author(s):  
Sanjoy K Paul ◽  
Olga Montvida ◽  
Jennie H Best ◽  
Sara Gale ◽  
Attila Pethö-Schramm ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Type 2 Diabetes ◽  
T Cell ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Therapy ◽  
Treatment Groups ◽  
Significant Difference ◽  
Necrosis Factor

ObjectiveTo explore possible associations of treatment with biological disease-modifying antirheumatic drugs (bDMARDs), including T-cell-based and interleukin-6 inhibition (IL-6i)-based therapies, and the risk for type 2 diabetes mellitus (T2DM) in patients with rheumatoid arthritis (RA).Study design, setting and participantsFive treatment groups were selected from a United States Electronic Medical Records database of 283 756 patients with RA (mean follow-up, 5 years): never received bDMARD (No bDMARD, n=125 337), tumour necrosis factor inhibitors (TNFi, n=34 873), IL-6i (n=1884), T-cell inhibitors (n=5935) and IL-6i+T cell inhibitor abatacept (n=1213). Probability and risk for T2DM were estimated with adjustment for relevant confounders.ResultsIn the cohort of 169 242 patients with a mean 4.5 years of follow-up and a mean 641 200 person years of follow-up, the adjusted probability of developing T2DM was significantly lower in the IL-6i (probability, 1%; 95% CI 0.6 to 2.0), T-cell inhibitor (probability, 3%; 95% CI 2.3 to 3.3) and IL-6i+T cell inhibitor (probability, 2%; 95% CI 0.1 to 2.9) groups than in the No bDMARD (probability, 5%; 95% CI 4.6 to 4.9) and TNFi (probability, 4%; 95% CI 3.7 to 4.7) groups. Compared with No bDMARD, the IL-6i and IL-6i+T cell inhibitor groups had 37% (95% CI of HR 0.42 to 0.96) and 34% (95% CI of HR 0.46 to 0.93) significantly lower risk for T2DM, respectively; there was no significant difference in risk in the TNFi (HR 0.99; 95% CI 0.93 to 1.06) and T-cell inhibitor (HR 0.96; 95% CI 0.82 to 1.12) groups.ConclusionsTreatment with IL-6i, with or without T-cell inhibitors, was associated with reduced risk for T2DM compared with TNFi or No bDMARDs; a less pronounced association was observed for the T-cell inhibitor abatacept.

scholarly journals Mortality in Patients with Brainstem Cavernous Malformations

2021 ◽  
pp. 1-7
Author(s):  
Julia Velz ◽  
Marian Christoph Neidert ◽  
Yang Yang ◽  
Kevin Akeret ◽  
Peter Nakaji ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Postoperative Mortality ◽  
Mortality Rates ◽  
Cavernous Malformations ◽  
Patient Cohort ◽  
Actual Risk ◽  
Single Center Study

<b><i>Objective:</i></b> Brainstem cavernous malformations (BSCM)-associated mortality has been reported up to 20% in patients managed conservatively, whereas postoperative mortality rates range from 0 to 1.9%. Our aim was to analyze the actual risk and causes of BSCM-associated mortality in patients managed conservatively and surgically based on our own patient cohort and a systematic literature review. <b><i>Methods:</i></b> Observational, retrospective single-center study encompassing all patients with BSCM that presented to our institution between 2006 and 2018. In addition, a systematic review was performed on all studies encompassing patients with BSCM managed conservatively and surgically. <b><i>Results:</i></b> Of 118 patients, 54 were treated conservatively (961.0 person years follow-up in total). No BSCM-associated mortality was observed in our conservatively as well as surgically managed patient cohort. Our systematic literature review and analysis revealed an overall BSCM-associated mortality rate of 2.3% (95% CI: 1.6–3.3) in 22 studies comprising 1,251 patients managed conservatively and of 1.3% (95% CI: 0.9–1.7) in 99 studies comprising 3,275 patients with BSCM treated surgically. <b><i>Conclusion:</i></b> The BSCM-associated mortality rate in patients managed conservatively is almost as low as in patients treated surgically and much lower than in frequently cited reports, most probably due to the good selection nowadays in regard to surgery.

The role of the GP in follow-up cancer care: a systematic literature review

2016 ◽  
Vol 10 (6) ◽  
pp. 990-1011 ◽  
Author(s):  
Judith A. Meiklejohn ◽  
Alexander Mimery ◽  
Jennifer H. Martin ◽  
Ross Bailie ◽  
Gail Garvey ◽  
...  
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Cancer Care

scholarly journals The Effectiveness of Rapamycin Combined with Eltrombopag in Murine Models of Immune-Mediated Bone Marrow Failure

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Rong Fu ◽  
Shaoxue Ding ◽  
Xiaowei Liang ◽  
Tian Zhang ◽  
Zonghong Shao
Keyword(s):  
Bone Marrow ◽  
Nk Cells ◽  
Standard Dose ◽  
Bone Marrow Failure ◽  
Statistical Significance ◽  
Murine Models ◽  
Immune Mediated ◽  
Tnf Α ◽  
Significant Difference ◽  
Ifn Γ

Recent research has found that Rapamycin (Rapa) was an effective therapy in mouse models of immune-mediated bone marrow failure. However, it has not achieved satisfactory effect in clinical application. At present, many studies have confirmed that Eltrombopag (ELT) combined with IST can improve the curative effect of AA patients. Then whether Rapa combined with Elt in the treatment of AA will be better than single drug application. In this study, we tested efficacy of Rapa combined with Elt as a new treatment in mouse models of immune-mediated bone marrow failure. Compared with AA group, the whole blood cell count of Rapa+Elt group increased significantly (Figure 1A) (P&lt;0.05). Survival of mice of Rapa+Elt group was significantly higher than that in the Rapa group (p &lt;0.01)(Figure 1B).There was no obvious difference in the numbers of NK cells and their subsets were noted in Rapa group,CsA group and Rapa+Elt group.The expression of NKG2D on peripheral functional NK cells was up-regulated in CsA group, Rapa group and Rapa+Elt group compared with AA group (P&lt;0.05). But there was no significant difference between effect of Rapa and CsA on the function of NK cells (Figure 1C).When Rapa combined with Elt, the expression of CD80 and CD86 are down-regulated more compared to Rapa group, but there is no statistical significance. Although these results suggested that Rapa+Elt had no statistical significance effect on numbers of mDC and expression of its functional molecule CD80 and CD86, the combined therapy still indicated that there is a potential synergy with immunosuppressant on AA mice to improve its outcome (Figure 1D).The results showed that CD4+/CD8+ ratio in CsA group, Rapa group, Rapa + Elt group had an obvious elevation than AA group (all P&lt;0.05). But there were no significant difference among the three groups on the CD4+/CD8+ ratio (Figure 1E,1F). As for INF-gamma, Rapa can reduce the secretion of IFN-γ from CD8+T cells with efficacy similar to that of the standard dose of CsA, and had a better outcome when combined with Elt in bone marrow failure mice (Figure 1E,1G).CsA group, Elt group, Rapa group, Rapa + Elt group showed notable increased ratio of Tregs compared with AA group, among which there were only Rapa group, Rapa + Elt group showed statistical significance(P&lt;0.05). for IL-10/Tregs ratio, Rapa group and Rapa +Elt group were superior to than CsA group(P&lt;0.05) (Figure 1H,1I).Rapa+Elt group and Rapa showed more lower level of IFN-γ compared with CsA group, and there was significant difference in Rapa+Elt group(P&lt;0.05). As for IL-10, IL-12p70, IL-2, IL-6, KC/GRO and TNF-α, the Rapa+Elt group showed more significant effect than Rapa or Elt alone(Figure1J). Thus, Rapa+Elt significantly down-regulated cytokines related to Th1 immune responses, such as IFN-γ, and upregulated cytokines related to Th2 immune responses, such as IL-10. To some extent, Rapa combined with Elt has a synergistic effect with CsA and Rapa alone in AA treatment. Conclusions In this study, Although Rapa combined with Elt had no significant improvement effect on the number and function of NK cells and their subsets, mDCs, and CD4+/CD8+ ratio in AA mice compared with Rapa alone, the Rapa+Elt can increase the secretion of IL-10 of Tregs and the number of Tregs, but has no significant effect on the number of Treg cells compared to with Rapa alone. Compared with AA group, the level of plasma IFN-γ, IL-2 and TNF-α decreased significantly (P&lt;0.05), but IL-10, IL-4, IL-5 and IL-1β increased significantly in Rapa group(P&lt;0.05). As for IL-10, IL-12p70, IL-2, IL-6, KC/GRO and TNF-α, the Rapa+Elt group showed more significant effect than Rapa alone. intervention treatment with Rapa in combination Elt in the AA mouse model more obviously ameliorated pancytopenia, improved bone marrow cellularity, and extended animal survival in a manner comparable to the standard dose of CsA and Rapa alone. Combination therapy support potential clinical utility in aplastic anemia treatment, which may further improve the efficacy of AA patients. Keywords: Rapamycin, Eltrombopag, murine models, bone marrow failure Figure 1 Disclosures No relevant conflicts of interest to declare.

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