Biologics Drugs in Behçet’s Disease: A Single Centre Experience

Introduction: Behçet´s disease (BD) is a systemic vasculitis of unknown cause. Several cytokines, such as tumor necrosis factor-alpha (TNF-α), appear to play a substantial role. Therefore, biologics such as anti-TNF-α agents are rising to control severe or refractory BD´s manifestations. We aimed to describe the biological therapy´s outcomes in BD patients. Methods: A longitudinal, prospective, unicentric cohort study with patients followed in a specialized outpatient clinic. We collected data regarding BD´s manifestations, treatments, and outcomes during follow-up. Results: Our cohort includes 243 patients, of whom 31% were male. During follow-up, 20 patients (8%) were treated with biological drugs. Patients who received biological therapies were younger (p = 0.030), had less frequently genital aphthosis (p = 0.009), and more frequently erythema nodosum (p = 0.009), polyarthritis (p = 0.002), spondyloarthritis (p = 0.024), retinal vasculitis (p = 0.011) and gastrointestinal manifestations (p = 0.024), namely gastroduodenal ulcer (p = 0.035), digestive bleeding from ulcers (p = 0.002), and bowel perforation (p = 0.004). Anti-TNF-α agents were used in all of these patients, most frequently infliximab. Patients started biologicals after classical immunosuppressors failure, and most went into remission (93%). Three patients developed tuberculosis during treatment, regardless of regular screening tests. It was possible to stop biological therapy in five patients, so far, without recurrence, with 33 months of mean follow-up time after suspension. Discussion: Anti-TNF-α agents are highly effective for refractory BD´s manifestations, although they are not innocuous. Little is known about the optimal duration of these therapies, regarding when and how to stop these drugs. This issue is essential not only to avoid relapses but also to reduce therapy side-effects.

Download Full-text

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3255 ◽

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

Download Full-text

Depressed Monocytic Activity may be a Predictor for Sepsis

Journal of Laboratory Physicians ◽

10.4103/0974-2727.154785 ◽

2015 ◽

Vol 7 (01) ◽

pp. 026-031 ◽

Cited By ~ 2

Author(s):

Nidhi Bhardwaj ◽

Purva Mathur ◽

Subodh Kumar ◽

Amit Gupta ◽

Deepak Gupta ◽

...

Keyword(s):

Blood Culture ◽

Bacterial Infections ◽

Trauma Patients ◽

Healthy Controls ◽

Necrosis Factor Alpha ◽

Trauma Population ◽

Immune Paralysis ◽

Tnf Α ◽

Causes Of Mortality

ABSTRACT Introduction: Trauma is one of the leading causes of mortality worldwide with infections as important causes of death in such patients. Bacterial infections cause activation of monocytes with excessive synthesis of pro-inflammatory cytokines. Hence, this prospective study was conducted to assess the activity of monocytes in traumatized sepsis patients using flow cytometry and to assess if they have any prognostic potential. Materials and Methods: A total of 16 consecutive trauma patients with sepsis and having positive blood culture were enrolled, along with four healthy controls during the period of March 2013 to July 2013. Blood from septic patients were collected on the same day when blood culture was positive and on days 2 and 5 thereafter. Surface staining for monocytes with CD14 and intracellular staining for interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) was done and results were analyzed by flow cytometer. Procalcitonin (PCT) assay was done using MiniVidas. Complete clinical follow-up was done for the patients. Results: Of the 16 patients, four died due to infections by various microorganisms. Isolated abdominal trauma (25%) was the most common injury among the enrolled patients of sepsis. Levels of TNF-α were significantly decreased when stimulated with lipopolysaccharide in the fatal patients as compared to the healthy controls. Patients having sepsis who survived had an increased level of TNF-α during the follow-up periods. Conclusion: This study showed that activity of monocytes to produce TNF-α and IL-6 were reduced in severe sepsis. Early identification of such immune-paralysis can help in earlier intervention to salvage this vulnerable trauma population.

Download Full-text

Risk of Non-Hodgkin Lymphoma Following Treatment of Inflammatory Conditions with Tumor Necrosis Factor-Alpha Inhibitors

Blood ◽

10.1182/blood.v126.23.2653.2653 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2653-2653

Author(s):

Gregory S. Calip ◽

Wan-Ju Lee ◽

Todd A. Lee ◽

Glen T. Schumock ◽

Brian C.-H. Chiu

Keyword(s):

Fusion Protein ◽

Tumor Necrosis ◽

Necrosis Factor Alpha ◽

Non Hodgkin Lymphoma ◽

Inflammatory Conditions ◽

Immunosuppressive Medications ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

Abstract Purpose Tumor necrosis factor-alpha (TNF-α) inhibitors are an increasingly common biologic treatment for moderate to severe inflammatory conditions such as psoriasis and rheumatoid arthritis. A limited number of studies and case reports of aggressive lymphoma and other malignancies in children and adolescent patients prompted a U.S. Food and Drug Administration black box warning for all TNF-α inhibitors. Although the two types of TNF-α inhibitors, anti-TNF monoclonal antibodies and TNF fusion protein, have similar clinical efficacy, their pharmacologic activity and modulation of immune pathways are different. Our objective was to examine and compare the incidence of non-Hodgkin lymphoma (NHL) among patients with inflammatory conditions treated with anti-TNF antibodies and TNF fusion protein. Patients and Methods We conducted a retrospective cohort study of new users of TNF-α inhibitors between 2009 and 2013 in the Truven Health MarketScan Research Database. Patients were included if they were ages 15+ years and had ≥12 months of continuous enrollment prior treatment initiation. Exclusion criteria included presence of any cancer, HIV or stem cell transplant in the year prior to first TNF-α inhibitor use. Using longitudinal pharmacy claims data, we measured continuous use of anti-TNF antibodies (infliximab, adalimumab, golimumab, certolizumab), TNF fusion protein (etanercept) and other immunosuppressive medications. NHL cases were identified using a validated algorithm with administrative claims and ICD-9 diagnosis codes. These data were also used to identify diagnoses of inflammatory conditions and calculate Charlson comorbidity index scores. NHL incidence rates per 100,000 person-years (PY) and 95% confidence intervals (CI) were calculated and compared to age-standardized expected rates in Surveillance, Epidemiology and End Results Program registries from the same time period and geographic regions with stratification by type of TNF-α inhibitor, gender and age group (15-39, 40-64, 65+ years). Standardized incidence ratios (SIR) and exact 95% CI were calculated using Poisson regression. NHL risk with use of anti-TNF antibodies was compared to etanercept use in multivariable Cox proportional hazards models. We estimated hazard ratios (HR) and 95% CI with adjustment for inflammatory conditions and concurrent immunosuppressive medications. Results In a cohort of 118,050 TNF-α inhibitor users, 85,327 (72%) used anti-TNF antibodies and 42,406 (36%) used TNF fusion protein alone or consecutively after switching TNF-α inhibitor type. The most prevalent indications for TNF-α inhibitors were rheumatoid arthritis (47%), followed by inflammatory bowel disease (23%), psoriasis (21%), psoriatic arthritis (15%) and ankylosing spondylitis (6%). During the 212,479 PY of follow-up, a total of 194 TNF-α inhibitor users developed NHL; and the crude NHL incidence rate (91 per 100,000 PY) was greater than expected (28 per 100,000 PY, age-standardized). Compared to non-cases, TNF-α inhibitor users that developed NHL were older (median age 59 vs. 48 years) and had more concurrent use of corticosteroids (77% vs. 56%) and methotrexate (48% vs. 37%). The overall age-standardized incidence ratio for NHL was 3.7 (95% CI 3.1-4.2) for TNF-α inhibitor users. Observed SIR was even higher in adolescent and young adult patients (15-39 years: SIR=7.3, 95% CI 4.5-11.3). Compared to etanercept users, patients treated with anti-TNF antibodies had greater risk of NHL (HR=1.5, 95% CI 1.1-2.0). This increased risk with anti-TNF antibodies was present in female users (HR=1.8, 95% CI 1.2-2.8) but less apparent in male users (HR=1.2, 95% CI 0.8-1.8). Conclusions In this large sample of patients treated with TNF-α inhibitors, we found higher incidence of NHL than expected in a similarly aged population and greater lymphoma risk with anti-TNF antibodies vs. etanercept. Further research with long-term follow up and clinical information on duration and severity of inflammatory conditions are needed to confirm these findings. Treatment of moderate to severe inflammatory conditions with TNF-α inhibitors is chronic and the potential lifetime exposure to these and other immunomodulating drugs is high, particularly for younger patients. Thus, determining the comparative safety of lymphoma among different types of TNF-α inhibitors has potentially significant implications and warrants continued evaluation. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Central Nervous System Demyelination Related to Tumour Necrosis Factor Alpha Inhibitor

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/20552173211070750 ◽

2022 ◽

Vol 8 (1) ◽

pp. 205521732110707

Author(s):

Shin Yee Chey ◽

Allan G. Kermode

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Tumour Necrosis ◽

Tumour Necrosis Factor Alpha ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

Background An association between tumour necrosis factor alpha (TNF-α) inhibitors exposure and central nervous system (CNS) demyelinating disorders has been postulated but is poorly understood. Objectives Describe the clinical spectrum and progress of a cohort of patients who developed demyelinating disorder following exposure to TNF-α inhibitor. Methods Retrospective chart review of patients who presented to a single neurologist in Western Australia between May 2003 and July 2020. Results 7 patients (6 females and 1 male) were identified. Mean age was 49.1 years. Mean follow-up time was 2.9 years. Mean interval between commencement of TNF-α inhibitor and onset of demyelinating event was 3 years. The spectrum of demyelinating events included transverse myelitis ( N = 3), acute brainstem syndrome ( N = 1) and optic neuritis ( N = 1). 2 patients had an atypical presentation but had MRI findings which unequivocally showed demyelinating changes. 2 patients had a monophasic event while the other 5 patients were diagnosed to have multiple sclerosis. All symptomatic patients with multiple sclerosis were started on disease modifying therapy and remained relapse free during follow-up. Conclusion Exposure to TNF-α inhibitor appears to increase the risk of demyelinating event. Whether TNFα inhibition directly results in CNS demyelination or trigger demyelination in susceptible individuals requires further research.

Download Full-text

Serum Levels of IL-17, IL-6, TNF-α and Disease Activity in Patients with Rheumatoid Arthritis

Aktuelle Rheumatologie ◽

10.1055/s-0035-1564141 ◽

2016 ◽

Vol 42 (04) ◽

pp. 323-328 ◽

Cited By ~ 1

Author(s):

M. Beyazal ◽

G. Devrimsel ◽

M. Cüre ◽

A. Türkyılmaz ◽

E. Çapkın ◽

...

Keyword(s):

Disease Activity ◽

Severe Disease ◽

Serum Levels ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

High Level ◽

Necrosis Factor

Abstract Objective: The aim of this study was to evaluate serum levels of interleukin (IL)-17, IL-6, and tumor necrosis factor alpha (TNF-α) in RA patients and to assess the correlation of these cytokines with clinical and laboratory parameters. Materials and Methods: 48 patients with RA and 35 healthy volunteers were enrolled in the study. Disease activity was determined by disease activity score (DAS28) in patients with RA. Patients with RA were categorized as mild (DAS28≤3.2), moderate (3.2<DAS28≤5.1), and severe (5.1<DAS28) according to DAS28. The serum levels of IL-17, IL-6 and TNF-α cytokines were measured by enzyme-linked immuno sorbent assay. Results: The mean serum IL-17 and TNF-α levels did not differ between RA patients and controls (P>0.05). Serum IL-6 levels were significantly elevated in RA patients compared with controls (P<0.001). The increasing trend in mean serum IL-6 levels across group with mild, moderate, and severe disease activity was significant (P<0.001, respectively). In RA patients, serum IL-6 concentrations were significantly correlated with ESR, CRP, DAS28, and VAS (r=0.371, P=0.009; r=0.519, P<0.001; r=0.536, P<0.001; r=0.539, P<0.001, respectively). Also, Serum IL-17 concentrations demonstrated significant correlations with ESR, CRP, but not DAS28 (r=0.349, P=0.015; r=0.299, P=0.039; r=0.274, P=0.060, respectively). Serum TNF-α showed no significant correlation with disease activity indices. Conclusions: This study showed that patients with RA had significantly increased cytokine level for IL-6, but not IL-17 and TNF-α and high level of serum IL-6 cytokine was associated with disease activity. However, further follow-up studies involving large samples are required to clarify precise role of these cytokines in disease development and progress.

Download Full-text

Safety and Efficacy of Vaccines during COVID-19 Pandemic in Patients Treated with Biological Drugs in a Dermatological Setting

Healthcare ◽

10.3390/healthcare9040401 ◽

2021 ◽

Vol 9 (4) ◽

pp. 401

Author(s):

Oriana Simonetti ◽

Giulio Rizzetto ◽

Elisa Molinelli ◽

Federico Diotallevi ◽

Giulia Radi ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Biological Therapy ◽

Previous History ◽

Biological Drugs ◽

Level Of Evidence ◽

Safety And Efficacy ◽

Tnf Α ◽

History Of ◽

Inactivated Vaccines ◽

Broad Overview

The BNT162b2 and mRNA-1273 vaccines, consisting of mRNA, have recently become available. The absolute novelty of these vaccines introduces questions about their safety and efficacy, especially in patients who are treated with biological drugs in dermatology. The aim of our review was to provide a broad overview of the current use of all available vaccinations in concomitance with biological therapy and to suggest indications for the new mRNA Covid-19 vaccines. We conducted a narrative review of the literature regarding the indications and safety of the various types of vaccines currently available in dermatological patients treated with biological therapy. The safety and efficacy of administering inactivated vaccines in patients undergoing biological therapy with inhibitors of TNF-α, IL-17, IL-12/23, and IL-4/13 was confirmed. Inactivated vaccines can be administered during therapy with inhibitors of IL-23 and IgE, taking into account that the level of evidence is lower due to the lack of specific studies. Live attenuated vaccines were contraindicated in concomitance with all biological therapies considered, except omalizumab. According to this evidence, we assume that there are currently no contraindications to the administration of the new Covid-19 BNT162b2 and mRNA-1273 vaccines during biological therapy with inhibitors of TNF-α, IL-17, IL-12/23, IL-23, and IL-4/13, since these vaccines are comparable to inactivated ones. For patients with chronic urticaria or allergic asthma treated with omalizumab, we currently recommend caution in using the mRNA Covid-19 vaccines (30 min observation). The only contraindications were a previous history of hypersensitivity to the Covid-19 vaccines themself or to their excipients. In conclusion, further randomized clinical trials are needed to evaluate the efficacy of the antibody response in these patients.

Download Full-text

Tumor Necrosis Factor-Alpha Inhibitor Medications for Inflammatory Conditions and Incidence of Multiple Myeloma

Blood ◽

10.1182/blood.v126.23.2954.2954 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2954-2954

Author(s):

Gregory S. Calip ◽

Wan-Ju Lee ◽

Todd A. Lee ◽

Glen T. Schumock ◽

Brian C.-H. Chiu

Keyword(s):

Fusion Protein ◽

Claims Data ◽

Incidence Rates ◽

Necrosis Factor Alpha ◽

Inflammatory Conditions ◽

Tnf Α ◽

Inflammatory Bowel ◽

Factor Alpha ◽

Necrosis Factor

Abstract Purpose Tumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine that regulates a wide variety of cellular responses including proliferation and differentiation. This potent mediator of inflammation and bone resorption is elevated in plasma of multiple myeloma (MM) patients, and inhibition of TNF-α is hypothesized to enhance the effects of MM treatments. However, the effects of TNF-α inhibitors on incidence of MM have not been fully characterized. Some reports indicate a possible increased risk of hematological malignancies with anti-TNF therapies. The purpose of this study was to examine incidence of MM among adults with inflammatory conditions treated with anti-TNF monoclonal antibodies and TNF fusion protein. Patients and Methods We conducted a retrospective cohort study of new users of TNF-α inhibitors from 2009-2013 using the Truven Health MarketScan Database. Patients were required to be 20+ years old and have 12 months of continuous enrollment prior to first TNF-α inhibitor use. Exclusion criteria included presence of the following in the year prior to first TNF-α inhibitor use: any malignancy, HIV+, and hematopoietic stem cell transplant. We used longitudinal pharmacy claims data to measure continuous use of infliximab, adalimumab, golimumab, certolizumab and etanercept, as well as other immunosuppressive medications. MM cases were identified using a validated algorithm for administrative claims data and ICD-9 diagnosis codes. Data from the year prior to first TNF-α inhibitor use were also used to calculate Charlson comorbidity index scores and document diagnoses of inflammatory conditions, including rheumatoid arthritis, psoriasis, psoriatic arthritis, inflammatory bowel disease (Crohn's disease, ulcerative colitis) and ankylosing spondylitis. Incidence rates of MM per 100,000 person-years (PY) with 95% confidence intervals (CI) were calculated for the cohort with stratification by gender, age group (20-49, 50-64, 65+ years) and type of TNF-α inhibitor (anti-TNF antibody, TNF fusion protein). Observed rates were compared to MM incidence rates from Surveillance, Epidemiology and End Results Program registries in the same time period and geographic regions. Standardized incidence ratios (SIR) and exact 95% CIs were calculated for those strata using Poisson regression. Results Among 114,045 incident users of TNF-α inhibitors, 82,003 (72%) used anti-TNF antibodies and 41,468 (36%) used TNF fusion protein alone or consecutively (after switching) during median follow up of 27 months and 205,635 PY overall. Rheumatoid arthritis (47%), psoriasis (21%) and inflammatory bowel disease (22%) were the most prevalent indications for TNF-α inhibitors, while fewer had psoriatic arthritis (15%) and ankylosing spondylitis (6%). There were 51 patients that developed MM during follow up, for a crude incidence rate (25 per 100,000 PY) that was higher than the expected rate (9 per 100,000 PY, age-standardized). TNF-α inhibitor users that developed MM were older (median: 57 vs. 49 years in non-cases) and had more concurrent treatment with corticosteroids (84% vs. 56%). The overall age-standardized incidence ratio for MM was SIR=3.2 (95% CI 2.4-4.2), with even higher than expected incidence in younger age groups (20-49 years: SIR=5.5, 95% CI 2.5-10.5; 50-64 years: SIR=8.0, 95% CI 5.1-11.5) but not in older patients (65+ years: SIR=1.8, 95% CI 1.0-3.1). Estimates were slightly higher for anti-TNF antibodies (SIR=3.6, 95% CI 2.6-5.0) vs. TNF fusion protein (SIR=2.8, 95% CI 1.6-4.5) and slightly lower in females (SIR=3.0, 95% CI 2.0-4.3) vs. males (SIR=3.5, 95% CI 2.3-5.2). Conclusions In this large sample of patients treated with TNF-α inhibitors, we observed a higher incidence of MM diagnoses than would be expected from a similarly aged population. Other than a causal association between TNF-α inhibitors and increased MM risk, a possible explanation for these findings could be the relationship between the underlying autoimmune, inflammatory conditions and myeloma etiology, particularly with the greater disease severity that would warrant these medications vs. other, non-biologic disease-modifying antirheumatic drugs (DMARDs). Future research on the comparative safety with long-term use of TNF-α inhibitors and other DMARDs that can incorporate clinical information on disease severity is needed to better understand these conditions, their treatment and subsequent MM risk. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Thalidomide in Axial Spondyloarthropathy: An Eastern Indian Experience

Bengal Physician Journal ◽

10.5005/jp-journals-10070-5202 ◽

2018 ◽

Vol 5 (2) ◽

pp. 3-6

Author(s):

Rudrajit Paul ◽

Arijit Sarkar ◽

Urmimala Bhattacharjee ◽

Ritasman Baisya ◽

Pallab Biswas ◽

...

Keyword(s):

Tertiary Care ◽

Human Leukocyte ◽

Limiting Factor ◽

Care Hospital ◽

Necrosis Factor Alpha ◽

Mediators Of Inflammation ◽

Axial Spondyloarthropathy ◽

Tnf Α ◽

One Year

ABSTRACT Background Axial spondyloarthropathy (SpA) is seronegative arthritis which mainly affects young adults and causes much morbidity. Tumor necrosis factor-alpha (TNF-α) is one of the main mediators of inflammation in joints and enthuses in SpA. Nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and biologics like TNF-α inhibitors are the mainstay of therapy in SpA. However, in India, the cost is one limiting factor in the use of biologics for the treatment of SpA in eligible patients. Thalidomide is an oral TNF-α inhibitor which has reported benefit in axial SpA, and it is a cheap option in the Indian setting. However, there is almost no Indian data on its efficacy. Materials and methods This is a retrospective analysis of patients receiving thalidomide for axial SpA in the rheumatology clinic of a tertiary care hospital of Kolkata. In this clinic, thalidomide was used at 100 mg/day. Patients receiving thalidomide, who had completed at least one year follow up were included in the analysis. Assessment of SpondyloArthritis International Society (ASAS)-20, ASAS-40, and ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP) were measured three monthly during the follow-up. Side effect profile of thalidomide was also recorded. Results The completed data of 66 patients were analyzed. All patients were human leukocyte antigen (HLA) B27 positive. Ninety-five point percent fulfilled ASAS-20 criteria at 12 months and 71.2% fulfilled the ASAS-40 criteria at 12 months. Three patients were nonresponders. The average ASDAS-CRP score also decreased from 2.9 to 1.5 over one year. Conclusion In our study, oral thalidomide resulted in significant improvements in axial SpA. Further randomized controlled trials are needed to find the relative efficacy of thalidomide with respect to other forms of treatment.

Download Full-text

FRI0477 SYSTEMIC TREATMENT IN SARCOIDOSIS. STUDY OF 377 PATIENTS FROM A SINGLE UNIVERSITY HOSPITAL

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3827 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 835.1-836

Author(s):

M. Calderón-Goercke ◽

R. Fernández-Ramón ◽

J. L. Martín-Varillas ◽

L. Sanchez-Bilbao ◽

D. Martínez-López ◽

...

Keyword(s):

Biological Therapy ◽

Systemic Treatment ◽

University Hospital ◽

Research Support ◽

Biological Drugs ◽

Systemic Corticosteroids ◽

Multisystemic Disease ◽

Granulomatous Diseases ◽

Treatment Of Sarcoidosis

Background:Sarcoidosis is a multisystemic disease characterized by the formation of non-necrotizing granulomas. The most frequently affected organs are lungs, skin and eyes. Systemic corticosteroids are the most used drugs in the treatment of this disease. Conventional and biological immunosuppressants (IS) may also be used(1-3).Objectives:To evaluate the systemic treatment of sarcoidosis according to clinical domains.Methods:Study of all consecutive patients diagnosed with sarcoidosis between 1/1/1999 and 1/1/2019 in a tertiary university hospital. The diagnosis was established following the ATS/ERS/WASOG criteria(Eur Respir J. 1999;14(4):735-737):compatible clinical and radiological presentation, evidence of non-caseifying granulomas and exclusion of other granulomatous diseases.Results:We studied 377 patients (188 men/189 women), mean age at diagnosis of 46.0±14.8 years. After a mean follow-up of 13.0±9.3 years, 161 (42.7%) patients did not require treatment. The remaining 216 (57.3%) received oral glucocorticoids (206, 54.6%) with a maximum mean dose of 43.2±19.0 mg/day, conventional IS (60, 16.2%), biological therapy (28, 7.4%) and/or endovenous methylprednisolone (15, 4.0%). Biological therapy was indicated by pulmonary (9, 32.1%), ocular (9, 32.1%), neurological (3, 10.7%), muskuloeskeletal (3, 10.7%), cutaneous (2, 7.1%), nephrological involvement (1, 3.6%); and Heerfordt’s syndrome (1, 3.6%). Adalimumab and Infliximab were the biologics used more frequently (Table).TABLESystemic treatment of sarcoidosis according to clinical domains.Conclusion:Compared to other studies, the high percentage of patients who required systemic treatment is remarkable. It also highlights the frequency of the use of biological drugs in more severe organ involvement (ocular and neurological), which is consistent with the trend in recent years.References:[1]Riancho-Zarrabeitia L, et al. Semin Arthritis Rheum. 2015; 45:361-8.[2]Vegas-Revenga N, et al. Am J Ophthalmol. 2019; 200:85-94.[3]Calvo-Río V, et al.. Clin Exp Rheumatol. 2014;32(4 Suppl 84): S54-7.Disclosure of Interests:Monica Calderón-Goercke: None declared, Raúl Fernández-Ramón: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Janssen and Celgene, Speakers bureau: Pfizer and Lilly, Lara Sanchez-Bilbao Grant/research support from: Pfizer, David Martínez-López: None declared, Iñigo González-Mazón: None declared, Jorge Javier Gaitán-Valdizán: None declared, Rosalía Demetrio-Pablo: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Download Full-text

Tumor Necrosis Factor Alpha (TNF-a) Blockade and Risk of Lymphoma: Systematic Review and Analysis of Literature

Blood ◽

10.1182/blood.v112.11.5278.5278 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5278-5278

Author(s):

Jeyanthi Ramanarayanan ◽

Shalu Pahuja ◽

Myron S Czuczman ◽

Francisco J. Hernandez-Ilizaliturri

Keyword(s):

Rheumatoid Arthritis ◽

English Language ◽

Critical Role ◽

Control Group ◽

Necrosis Factor Alpha ◽

Inflammatory Disorders ◽

Number Of Patients ◽

Increased Risk ◽

Tnf Α

Abstract BACKGROUND: TNF-α plays a critical role in the regulation of cytokine mediated cancer immunosurveillance. Evidence suggests that depletion of TNF-α may result in abrogated anti-tumor immunity and increase in the risk of malignancies. Anti-TNF-α therapy (infliximab, adalimumab and etanercept) is known to halt the progression of certain inflammatory disorders and has been approved for the treatment of at least five autoimmune/inflammatory conditions. Given the widespread use of these biological agents, it is vital to explore the associated increased risk of malignancies especially lymphoma. OBJECTIVE: Risk of lymphoma associated with anti-TNF-α therapy is controversial in rheumatoid arthritis (RA) and has not been extensively studied in other inflammatory disorders. With the expanding role of anti-TNF-α therapy, we evaluated the risk of lymphoma among all approved indications for which they are currently in use. METHODOLOGY: We conducted a systematic electronic search of MEDLINE using the terms TNF-α, infliximab, adalimumab, etanercept, rheumatoid, psoriasis, arthritis, inflammatory bowel disease, ankylosing spondylitis from January 1998 to December 2007. Studies analyzed were restricted to those in English language, full text published articles, randomized controlled trials (RCT), meta-analysis (MT), review articles, extension studies, reports from national databases (ND) and postmarketing surveillance studies. Risk of lymphoma from ND was obtained as odds ratio with 95% confidence interval. Incidence of lymphoma reported from RCT was analyzed as percentage fraction of the total number of patients enrolled in the study and follow up. RESULTS: Overall 51 studies (2 MT, n=10,370; 4 ND, n=29,099 and 45 RCT, n=54,637) that included anti-TNF-α therapy in inflammatory disorders were analyzed. Treatment/follow up period were variable from 12 weeks to 8 years. Ten patients (0.09%) from MT treated with anti-TNF-α therapy developed lymphoma vs 0 in the non-anti-TNF-α group. Report from one of the 3 ND showed an increased risk (11.5 RR 95% CI 3.7–26.9) of lymphoma among the anti-TN-α exposed group. Among the RCT, 16 patients (0.02%) in the anti-TNF-α group developed lymphoma vs 3 (0.005%) in the control group. CONCLUSION: Existing data suggests that anti-TNF-α therapy in rheumatoid arthritis is associated with an increased risk of lymphoma but this may be attributed to the severity of the disease itself. Among other inflammatory disorders, a rise in lymphoma risk could not be established. Whether anti-TNF-α therapy in the long term can in fact decrease the incidence of lymphoma by altering the disease severity remains to be determined.

Download Full-text