scholarly journals POS0488 THE IMPACT OF ANTINUCLEAR ANTIBODIES INDUCED BY ANTI-TUMOUR NECROSIS FACTOR ALPHA AGENTS ON THE LONG-TERM TREATMENT OUTCOMES IN RHEUMATOID ARTHRITIS PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 476.2-477
Author(s):  
D. Santos Oliveira ◽  
A. Martins ◽  
F. R. Martins ◽  
M. Rato ◽  
F. Oliveira Pinheiro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Response ◽  
Response To Treatment ◽  
Eular Response ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Switch Rate ◽  
Factor Alpha ◽  
The Impact

Background:The seroconversion of antinuclear antibodies (ANA) induced by anti-tumour necrosis factor alpha (anti-TNF-α) therapy remains a matter of concern in various inflammatory conditions namely rheumatoid arthritis. However, evidence is still scarce regarding the impact of these autoantibodies on the clinical response to treatment in these patients.Objectives:This study aimed to explore the impact of ANA induced by anti-TNF-α therapy on the outcomes of treatment in patients with rheumatoid arthritis over two years of follow-up.Methods:An observational retrospective cohort study was conducted with two years of follow-up. Patients diagnosed with rheumatoid arthritis, according to the American College of Rheumatology (ACR) criteria, and registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα agent as first biologic between 2003 and 2018 were included. Patients with positive ANA (titer ≥100) and/or positive anti-double stranded DNA (anti-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. Disease Activity Score for 28 joints (DAS28), DAS28 delta, Health Assessment Questionnaire (HAQ), HAQ delta were assessed at baseline, 6, 12, 18 and 24 months. Clinical response was evaluated by EULAR criteria and three response categories were defined: good, mild and no response. The rate of switch of biological treatment was assessed over 24 months. To examine the differences between groups with and without ANA seroconversion independent samples t test for normally distributed continuous data, Mann-Whitney U-tests for non-normally distributed continuous data and Chi-square tests for categorical data were used. Logistic regression models were used to assess the effects of ANA seroconversion on clinical response to treatment over 6, 12, 18 and 24 months.Results:A total of 185 patients (mean age of 49.3±10.9 years old; 85.4% female) with a median follow-up of 7 [4-14] years were included. We found an ANA seroconversion rate (titer ≥100) of 77.3% (n=143) with median time of 36 [15-72.3] months. There were no differences among groups regarding age, gender, disease duration, be seropositivity or not (for rheumatoid factor and/or anti-citrullinated protein antibodies) and have an erosive disease or not. DAS28 delta was significantly different (p=0.035) between group with positive ANA (2.01±1.29) and negative ANA (1.15±1.51) at 6 months. DAS28 was significantly different (p=0.014) between group with positive ANA (5.06±3.39) and negative ANA (3.99±1.43) at 12 months. No statistically significant differences were found in the DAS28, DAS28 delta, HAQ, HAQ delta at 18 and 24 months and in the EULAR response at any time. Switch rate was significantly different between patients with ANA seroconversion (median 1[0-1]) versus absence of seroconversion (median 0[0-1]), p=0.025. In the regression model ANA seroconversion did not predict switch rate and EULAR response over time.Conclusion:This study showed that the majority of patients with rheumatoid arthritis treated with an anti-TNF-α agent developed ANA and that their presence may be associated with worse clinical results (DAS28) at 6 and 12 months. In fact, previous research suggested that a decrease in anti-TNF-α drug concentration due to the production of autoantibodies may lead to worse outcomes of treatment. Moreover, our data demonstrated that patients with ANA seroconversion had a higher switch rate. Despite these results, there are no differences in the EULAR response between the two groups and ANA seroconversion did not predict this response over time. Therefore, ANA induced by anti-TNF-α agents should be monitored in patients with rheumatoid arthritis and its impact on treatment must be considered. Further research is needed to explore these results through large-scale prospective studies.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 The Use of Rheumatic Disease Comorbidity Index for Predicting Clinical Response and Retention Rate in a Cohort of Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Alpha Inhibitors

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Martina Biggioggero ◽  
Federica Mesina ◽  
Ennio Giulio Favalli
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Response ◽  
Tumor Necrosis ◽  
Retention Rate ◽  
First Line ◽  
Necrosis Factor Alpha ◽  
Comorbidity Index ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Moderate Response

Introduction. To retrospectively evaluate the impact of comorbidities on treatment choice, 12-month clinical response, and 24-month retention rate in a cohort of patients with rheumatoid arthritis (RA) treated with a first-line tumor necrosis factor alpha inhibitor (TNFi), by using for the first time the Rheumatic Disease Comorbidity Index (RDCI). Methods. The study population was extracted from a local registry of RA patients receiving adalimumab or etanercept as first-line biologics between January 2001 and December 2013. The prevalence of comorbidities was computed, and patients were stratified according to RDCI for evaluating the role of comorbidities on TNFi choice, concomitant methotrexate, clinical response (1-year DAS28-ESR remission and low disease activity [LDA] and EULAR good-moderate response), and the 24-month retention rate. Results. 346 patients (172 adalimumab and 174 etanercept) were included. A significantly higher EULAR good/moderate response (P = 0.020) and DAS28-ESR remission (P = 0.003) were obtained according to RDCI (0, 1, 2, or ≥3). Lower RDCI (P = 0.022), male sex (P = 0.006), higher baseline DAS28-ESR (P = 0.001), ETN (P < 0.001), and concomitant methotrexate (P = 0.016) were predictors of EULAR good/moderate response. Elevated RDCI was a predictor of discontinuation of biologics (P = 0.036), whereas treatment with etanercept (P < 0.001) and methotrexate (P = 0.007) was associated with a lower risk of TNFi withdrawal. Conclusions. Multimorbidity, measured by RDCI, is a negative predictor of TNFi persistence on treatment and of achieving a good clinical response. The use of RDCI may be very useful for identifying patients with RA carrying those comorbid conditions associated with poor prognostic outcomes and for defining new treatment targets in multimorbid RA patients.

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

Blood ◽  
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.

scholarly journals Central Nervous System Demyelination Related to Tumour Necrosis Factor Alpha Inhibitor

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.

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

2016 ◽  
Vol 42 (04) ◽  
pp. 323-328 ◽  
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.

scholarly journals Modulation of Anti-Tumor Necrosis Factor Alpha (TNF-α) Antibody Secretion in Mice Immunized with TNF-α Kinoid

2012 ◽  
Vol 19 (5) ◽  
pp. 699-703 ◽  
Author(s):  
Eric Assier ◽  
Luca Semerano ◽  
Emilie Duvallet ◽  
Laure Delavallée ◽  
Emilie Bernier ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Necrosis Factor Alpha ◽  
Neutralizing Capacity ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTTumor necrosis factor alpha (TNF-α) blockade is an effective treatment for patients with TNF-α-dependent chronic inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis. TNF-α kinoid, a heterocomplex of human TNF-α and keyhole limpet hemocyanin (KLH) (TNF-K), is an active immunotherapy targeting TNF-α. Since the TNF-K approach is an active immunization, and patients receiving this therapy also receive immunosuppressant treatment, we evaluated the effect of some immunosuppressive drugs on the generation of anti-TNF-α antibodies produced during TNF-K treatment. BALB/c mice were injected intramuscularly with TNF-K in ISA 51 adjuvant. Mice were also injected intraperitoneally with one of the following: phosphate-buffered saline, cyclophosphamide, methylprednisolone, or methotrexate. Anti-TNF-α and anti-KLH antibody levels were assessed by enzyme-linked immunosorbent assay and the anti-TNF-α neutralizing capacity of sera by L929 bioassay. Our results showed that current treatments used in rheumatoid arthritis, such as methylprednisolone and methotrexate, do not significantly alter anti-TNF-α antibody production after TNF-K immunization. In contrast, the administration of cyclophosphamide (200 mg/kg) after immunization significantly reduced anti-TNF-α antibody titers and their neutralizing capacity.

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

Blood ◽  
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.

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