Incidence Rates Of Malignancies Research Articles

OP0124 RISK OF MALIGNANCIES ACROSS BIOLOGIC CLASSES IN RHEUMATOID ARTHRITIS: ANALYSIS OF A NATIONAL CLAIM DATABASE

Background:Objectives:To estimate the incidence rate of malignancies in biologic-treated RA patients, and to compared it to the general population and across different classes of biologicsMethods:We conducted an historical cohort study within the French the national claim database, named SNDS. This database prospectively records individual health resource of 86% of the entire French population (65 million inhabitants) since 2007. RA adult patients were identified based on ICD-10 code (M05 or M06). Patients with cancer history were excluded. Treatment exposures focused on incident first use of biologics including all anti-TNF, rituximab, abatacept, tocilizumab, ustekinumab, anakinra. To identify incident treatment periods, only patients who did not receive any biologics in the 1-year period before the index date were selected. In the base case analysis, exposure was defined with a 90-day latency after treatment initiation and a 180-day carry-over period after drug discontinuation.To compare the risk of malignancies between biologic treated patients and general population, Standardized incidence ratio (SIR [95%CI]) were calculated using FRANCIM (“France Cancer Incidence et Mortalité”) estimations as reference.To compare the risk of malignancies between biologics, a propensity score (including age, sex, year of first occurrence of RA code, date of treatment initiation, number of previous DMARDs, Charlson comorbidity index, diagnosis of tobacco and/or alcohol-associated disorders, number of hospitalizations for RA, cumulative corticosteroid dose) was calculated for each comparison. Hazard Ratios (HRs) for risk of cancer were estimated using Cox proportional hazard model using inverse probability of treatment weighting (IPTW) with propensity score. Exposure was considered as a time-dependent variable and propensity scores were estimated dynamically using pooled logistic regression reassessed for each new exposure.Results:Between 2007 and 2016, 31,792 patients (112,802 patient-years)- were exposed to biologics. The annual incidence rate of overall malignancies was 0.865 per 100 patients-years. Malignancies occurred in 730 patients exposed to anti-TNF, 235 patients exposed to another biologic and 11 exposed to both.As compared to the general population, biologic treated patients had an increased risk of lung cancer (SIR=1.35 [1.14;1.60]), a decreased risk of pancreatic cancer (SIR=0.52[0.31-0.85]) and no significant increased risk of invasive melanoma (SIR=1.15 [0.82;1.61]). Results were similar for anti-TNF-treated patients. Other biologics were not analyzed separately due to small sample sizes.The overall risk of malignancies and risk of lymphoma did not differ between anti-TNF and other biologics (analysed all together), or abatacept. Within the anti-TNF class, the overall risk of malignancies and risk of lymphoma did not differ between etanercept and monoclonal anti-TNF (table).Type of malignanciesHR [95% CI]p-valueHR [95% CI]p-valueHR [95% CI]p-valueAnti-TNF (ref) vs. other biologicsAnti-TNF (ref) vs. AbataceptMonoclonal anti-TNF (ref) vs. EtanerceptP-Y exposure83256 vs. 2564991770 vs. 468149620 vs. 36790All malignancies (excl. non-melanoma skin cancer)0.97 [0.81;1.17]p=0.71.27 [0.89;1.81]p=0.21.11 [0.94;1.32]p=0.2Solid cancer (excl. non-melanoma skin cancer)0.98 [0.80;1.20]p=0.81.23 [0.84;1.82]p=0.41.10 [0.92;1.32]p=0.3Lymphoma0.69 [0.32;1.46]p=0.31.73 [0.55;5.48]p=0.50.87 [0.49;1.57]p=0.7Conclusion:Using a large nationwide healthcare database, representative of the French population, the overall risk of malignancies did not seem to differ across the different classes of biologic. Among anti-TNF, the risk of malignancies of lymphoma did not differ between etanercept and monoclonal antibodies. The risk of organ specific cancers, except lung cancer, did not differ from that of general population.Disclosure of Interests:Raphaèle Seror Consultant of: BMS, Medimmune, Novartis, Pfizer, GSK, Lilly, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Alexandre Lafourcade: None declared, yann de-rycke: None declared, Xavier Mariette Consultant of: BMS, Gilead, Medimmune, Novartis, Pfizer, Servier, UCB, Florence Tubach Grant/research support from: Florence TUBACH is head of the Centre de Pharmacoépidémiologie (Cephepi) of the Assistance Publique – Hôpitaux de Paris and of the Clinical Research Unit of Pitié-Salpêtrière hospital, both these structures have received research funding, grants and fees for consultant activities from a large number of pharmaceutical companies, that have contributed indiscriminately to the salaries of its employees. Florence Tubach didn’t receive any personal remuneration from these companies.

P220 An updated safety profile of baricitinib for the treatment of RA up to 7 years

Abstract Background Baricitinib (BARI) is a selective inhibitor of janus kinase (JAK) 1 and JAK2, approved for the treatment of moderately to severely active rheumatoid arthritis (RA) in adults in over 50 countries. Objective: To evaluate the long-term safety of BARI in patients with RA with a specific focus on malignancies, major adverse cardiovascular events (MACE), serious infections and herpes zoster (HZ) events. Methods Data from nine completed studies (5 Phase 3, 3 Phase 2, 1 Phase 1b) and 1 long term extension (LTE) study were pooled for this analysis (data cut-off date: 13-Feb-2018). The all BARI data set included all patients exposed to any BARI dose. Results A total of 3,770 patients with RA were treated with BARI (10,127 patient years [PY]) with a maximum exposure of 7 years. Of these, 2,938 (78%) and 1,754 (47%) were on concomitant methotrexate or corticosteroids (CS; mean dose 6.2 mg/day), respectively. The incidence rates (IR) of malignancy (excluding non-melanoma skin cancer) were 0.8 (2-mg) and 1.0 (4-mg; as-randomized analysis) in the LTE. The IRs for MACE were similar between the all BARI and PBO group; however, the IR for DVT/PE were numerically higher in the BARI 4mg group during the PBO-controlled period. IRs for MACE remain stable over time. The IR of serious infections were numerically higher in the PBO group; the IR of tuberculosis and other opportunistic infections were similar between the all BARI and PBO group. During the PBO-controlled period, HZ IR was significantly higher for BARI 4-mg versus PBO (4.4 vs 1.1) (Table 1). Amongst 323 HZ patients, 11 (4%) had received prior HZ vaccination. Twenty-six [8%] cases were multidermatomal, and no visceral disease was reported. Multivariate analyses showed that older age and some geographical regions (Asia, especially Japan, Taiwan and South Korea) were associated with a higher risk of HZ. Conclusion This integrated analysis in patients with active RA exposed to BARI for up to 7 years shows that the safety profile of BARI is like that reported previously. The IRs of malignancies, MACE (including DVT/PE), serious infection, and HZ did not increase over time. Disclosures D. Walker: Honoraria; Lilly, Pfizer, Giliad, Novartis, Roche. Member of speakers’ bureau; Lilly, Pfizer, Roche. I. Kouris: Other; Lilly employee. T. Holzkämper: Shareholder/stock ownership; Lilly. Other; Lilly employee. M.W. Wu: Other; Lilly employee. R. Xavier: None. J. Smolen: Consultancies; Abbvie, Amgen, Astra Zeneca, Astro, BMS. Grants/research support; Abbvie, Eli Lilly, Novartis, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB. P. Durez: Member of speakers’ bureau; Abbvie, BMS, Celltrion, Eli Lilly. Y. Chen: None. J. Zhong: Corporate appointments; Eli Lilly Contractor. R. Liao: Other; Lilly employee. M.C. Genovese: Consultancies; Eli Lilly. K. Winthrop: Consultancies; Pfizer, UCB, Eli Lilly, Gilead, Abbvie, Roche, BMS.

Urological malignancy incidence rates over time by county rurality.

750 Background: Approximately 20% of the U.S. population resides in non-metropolitan (rural) areas. We aimed to evaluate urological cancer incidence among populations residing in metropolitan (metro) and rural counties, categorized by adjacency to a metro area. Methods: Using data from CDC’s National Program of Cancer Registries and NCI’s Surveillance, Epidemiology, and End Results Program, we compared incidence rates of prostate (PCa), kidney (KCa), and bladder (BCa) cancers diagnosed during 2007–2011 and 2012–2016 among adults age ≥ 20 years residing in metro and rural counties, as designated by rural-urban continuum codes. Rural counties were divided into those adjacent to a metro area (Rural-A) and those not adjacent to a metro area (Rural-NA). For the time period studied, these data cover approximately 97% of the US population. Rates were age-adjusted to the 2000 U.S. standard population. Results: We identified 1,980,168 PCa, 541,225 KCa, and 688,562 BCa cases newly diagnosed during 2007–2016. Patients from rural-A counties comprised 11% of all cases, rural-NA counties 6%, and metro counties 83%. Table shows the age-adjusted incidence per 100,000 with 95% confidence intervals. Overall, PCa and BCa incidence decreased over time; KCa incidence increased. PCa exhibited higher incidence rates in metro areas; KCa and BCa had higher incidence rates in rural counties (Table). Conclusions: Rural counties have higher BCa and KCa incidence relative to metro counties, but lower PCa incidence. Changes in PCa screening practices may have contributed to decreases in PCa incidence. Further investigation is needed to understand how rurality influences KCa and BCa epidemiology. Disclaimer: The findings and conclusion of this report are those of the authors and do not represent the official position of the CDC.[Table: see text]

The 5-year Tysabri global observational program in safety (TYGRIS) study confirms the long-term safety profile of natalizumab treatment in multiple sclerosis

BackgroundNatalizumab is an effective treatment for multiple sclerosis (MS) and has a well-characterized safety profile, with more than 10 years of postmarketing experience. TYGRIS was a 5-year observational cohort study designed to obtain long-term safety data in natalizumab-treated MS patients. We examined the incidence and pattern of serious adverse events (SAEs) in this large postmarketing sample of natalizumab-treated patients. MethodsInvestigators reported SAEs in natalizumab-treated patients. Malignancy incidence rates were compared with rates in the general population using external databases. ResultsOf 6508 enrolled patients, 4938 (75.9%) completed the study. SAEs occurring in more than 0.5% of patients included urinary tract infection (n = 50; 0.8%), pneumonia (n = 46; 0.7%), progressive multifocal leukoencephalopathy (PML; n = 44; 0.7%), and immune reconstitution inflammatory syndrome (n = 44; 0.7%). Fifty-five patients (0.9%) experienced treatment-emergent serious opportunistic infections, 44 of which were PML. Two patients with PML died. The overall malignancy incidence rate was 449.0 per 100,000 patient-years (95% confidence interval [CI], 375.1–533.1). With few exceptions, incidence rates for individual malignancies had 95% CIs encompassing incidence rates in the general population. Hepatotoxic events occurred in 6 patients; 4 patients had evidence of alternative cause or confounders. Of 96 fatal events, investigators considered 81 unrelated or unlikely to be related to treatment and 5 related or possibly related; causality was not provided for 10. ConclusionData from this large, long-term study indicate that the nature, character, and frequency of SAEs in real-world settings are consistent with natalizumab's known safety profile. (Funded by Biogen; ClinicalTrials.gov identifiers: NCT00477113 and NCT00483847.)

Long-term safety of certolizumab pegol in rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis and Crohn’s disease: a pooled analysis of 11 317 patients across clinical trials

ObjectiveTo review long-term certolizumab pegol (CZP) safety across all approved indications: rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn’s disease (CD).MethodsData were pooled across 49...

Risk of malignancy associated with use of tocilizumab versus other biologics in patients with rheumatoid arthritis: A multi-database cohort study

ObjectivesTo examine the rate of incident malignancies excluding non-melanoma skin cancer (NMSC) in patients with rheumatoid arthritis (RA) newly treated with tocilizumab versus other biologic drugs. MethodsWe conducted a cohort study using data from 3 U.S. insurance claims databases – Medicare (2010–2015), ‘IMS’ PharMetrics Plus (2011–2015) and Truven ‘MarketScan’ (2011–2015). Adults with RA who newly started tocilizumab or a TNF inhibitor (TNFi) after failing a different TNFi, abatacept or tofacitinib were included. The primary outcome was development of any malignancies excluding NMSC. For confounding control, tocilizumab starters were propensity score (PS)-matched to TNFi starters with a variable ratio of 1:3 within each database. Hazard ratios (HR) from the 3 PS-matched cohorts were combined by an inverse variance-weighted, fixed-effects model. We conducted a secondary analysis where we compared tocilizumab initiators with abatacept initiators. ResultsWe included 13,102 tocilizumab initiators PS-matched to 26,727 TNFi initiators in all three databases. The incidence rate of malignancies per 1,000 person-years ranged from 8.27 (IMS) to 23.18 (Medicare) in the tocilizumab group and from 9.64 (MarketScan) to 21.46 (Medicare) in the TNFi group. The risk of incident malignancies was similar between tocilizumab and TNFi initiators across all three databases, with a combined HR of 0.98 (95%CI 0.80–1.19) in tocilizumab versus TNFi. The secondary analysis comparing tocilizumab versus abatacept showed similar results (combined HR 0.97, 95%CI 0.74–1.27). ConclusionsThis large multi-database cohort study found no difference in the risk of malignancies excluding NMSC in RA patients who newly started tocilizumab compared with TNFi or abatacept.

Adalimumab Effectiveness Up to Six Years in Adalimumab-naïve Patients with Crohn's Disease: Results of the PYRAMID Registry.

BackgroundPYRAMID was an international multicenter, noninterventional, postmarketing registry assessing long-term safety and effectiveness of adalimumab (Humira), as used in routine clinical practice.MethodsAdult patients with moderately to severely active Crohn’s disease with or without prior adalimumab experience were enrolled in the registry and followed for up to 6 years. Effectiveness measurements included the Physician’s Global Assessment (PGA, a composite of Harvey Bradshaw Index [HBI] and rectal bleeding score), clinical remission (HBI < 5), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and Work Productivity and Activity Impairment (WPAI) questionnaire. Data were reported for adalimumab-naïve patients and analyzed by baseline immunomodulator use and disease duration.ResultsThis study evaluated 2057 adalimumab-naïve patients. Mean PGA improved from 7.5 (baseline) to 3.9 (year 1) and 3.3 (year 6). The proportion of patients in HBI remission increased from 29% (573 of 1969; baseline) to 68% (900 of 1331; year 1) and 75% (625 of 831; year 6). Patients stratified by baseline immunomodulator use had similar HBI remission rates; patients with disease duration <2 years achieved numerically higher HBI remission rates than patients with longer disease duration. Patient-reported SIBDQ and WPAI scores improved at year 1; all WPAI subscore improvements were clinically meaningful (≥7% point change) at year 1 and maintained through year 6. Serious infections were reported in 11.1% of patients; incidence rates of malignancies, lymphoma, and demyelinating disorders were low.ConclusionAdalimumab therapy, as used in routine clinical practice, improved physician-reported and patient-reported disease outcomes and remission rates for up to 6 years. No new safety signals were observed.

Higher risk of malignant neoplasms in young adults with end-stage renal disease receiving haemodialysis: A nationwide population-based study.

ABSTRACTAimPrevious investigations have shown that end‐stage renal disease (ESRD) is associated with an increased risk of malignancies. The aim of this study was to explore the association between ESRD in patients undergoing maintenance haemodialysis (HD) and the incidence of malignancies according to age.MethodsWe analysed a nationwide cohort retrieved from Taiwan's National Health Insurance Research Database to study the incidence of malignancies in patients who were and were not receiving HD. One million beneficiaries were randomly selected and followed from 2005 to 2013. Of these 1 000 000 patients, 3055 developed ESRD and commenced maintenance HD during this period. For each HD patient, four age‐, gender‐ and diabetes‐matched controls were selected from the database (n = 12 220). We further stratified the patients according to age. The study endpoint was the occurrence of malignancy.ResultsThe incidence rates of malignancy were 6.8% and 4.9% in the HD and control groups, respectively. Competing risk regression analysis indicated that age, HD, male gender and diabetes were associated with an increased risk of malignancy. When further stratified according to age, the odds ratios of developing cancer were 5.8, 1.9, 1.9 and 1.5 among the HD patients aged <40 years, 40–49 years, 50–59 years and 60–69 years, respectively.ConclusionThe patients with ESRD who received HD had a significantly higher cumulative risk of malignancy, especially those with a young age. Therefore, specialized cancer screening protocols for young HD patients might help to prolong their lifespan.

Infliximab Is Not Associated With Increased Risk of Malignancy or Hemophagocytic Lymphohistiocytosis in Pediatric Patients With Inflammatory Bowel Disease

Immunosuppressive therapy for inflammatory bowel disease (IBD) in pediatric patients is thought to increase the risk of malignancy and lymphoproliferative disorders, including hemophagocytic lymphohistiocytosis (HLH). We compared unadjusted incidence rates of malignancy and HLH in pediatric patients with IBD exposed to infliximab (IFX) with patients not exposed to biologics and calculated standardized incidence ratios (SIRs). We collected and analyzed data from 5766 participants in a prospective study of long-term outcomes of pediatric patients with IBD (NCT00606346), from May 31, 2007 through June 30, 2016. Patients were 17 years old or younger and had Crohn's disease, ulcerative colitis, or IBD-unclassified with 24,543.0 patient-years of follow-up. We estimated incidence rates for malignancy and HLH as events/1000 patient-years of follow-up. We calculated age-, sex-, and race-adjusted SIRs, with 95% confidence intervals (CIs), using the Surveillance, Epidemiology, and End Results Program (SEER) database. Thirteen of the 15 patients who developed a malignancy and all 5 of the patients who developed HLH had been exposed to thiopurines; 10 patients with malignancy had also been exposed to a biologic agent. Unadjusted incidence rates showed no increased risk of malignancy (0.46/1000 patient-years) or HLH (0.0/1000 patient-years) in patients exposed to IFX asthe only biologic vs those unexposed to biologics (malignancy: 1.12/1000 patient-years; HLH: 0.56/1000 patient-years). SIRs did not demonstrate an increased risk of malignancy among patients exposed to IFX (SIR, 1.69; 95% CI, 0.46-4.32) vs patients not exposed to a biologic agent (SIR, 2.17; 95% CI, 0.59-5.56), even when patients were stratified by thiopurine exposure. In determination of age-, sex-, and race-adjusted SIRs using data from a large clinical study and the SEER database, we found that IFX exposure did not associate with increased risk of malignancy or HLH in pediatric patients with IBD. Thiopurine exposure is an important precedent event for the development of malignancy or HLH in pediatric patients with IBD.

Thyroid cancer and nodular goiter of thyroid: An analysis of patients in rural South Tamil Nadu

Background: The aim of the study was to analyze the profile of nodular goiters of thyroid presenting with thyroid cancers in a tertiary hospital in rural South India. Materials and Methods: This study was conducted for 2 years since 2010 in patients with thyroid enlargements. Patients with multinodular or solitary thyroid enlargements with ultrasonogram suspicious of malignancy, fine-needle aspirate suspicious of malignancy, or persons with clinical suspicious thyroid enlargements with equivocal ultrasonogram or cytology with or without symptoms of mass effect were selected for the study. The clinical, operative, cytological, and histological data were tabulated and statistically analyzed. Results: Of 522 patients analyzed, 91.57% were females and 67.62% were between 21 and 40 years. Nearly 17.04% presented with hypothyroidism, 15.13% with hyperthyroidism, and 67.82% patients were euthyroid. Of the 522 patients, 425 (81.42%) had nodular thyroid enlargements, of whom 224 (42.91%) had multinodular goiters (MNGs), 201 (38.51%) had solitary thyroid nodules (SNT), and 97 (18.58%) had diffuse thyroid enlargements. The malignant tumors were present in 105 patients with papillary carcinoma, 20 patients with follicular carcinoma, and 6 with medullary carcinoma, of whom 76 (33.93%) had MNG and 54 (26.87%) had SNT. Conclusion: Thyroid cancers are best diagnosed through concerted clinical, radiological, cytological, and histological analyses. All nodules of thyroid, whether solitary or multinodular, should be sampled in fine-needle aspiration under radiological assistance and similarly all nodules need to be studied for malignancy in histopathology. In this study, we observed that the incidence rates of malignancy were higher than that of the existing Indian data and these patients were from the coastal regions of Tirunelveli and Thoothukudi districts. We also observed that multinodular goiters had microscopic malignant foci.

Risk for malignancy in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs compared to the general population: A nationwide cohort study in Japan

Objectives: To investigate and compare the risk for malignancy in rheumatoid arthritis (RA) patients treated with biologics in Japan to the general population.Methods: Data for 14,440 patients from 335 institutions who were given infliximab, etanercept, adalimumab, golimumab, tocilizumab, or abatacept were retrieved from the SafEty of biologics in Clinical Use in Japanese patients with RhEumatoid arthritis (SECURE) database.Results: We identified 333 incidents of malignancies in 320 patients during 49,320 patient-years (PY). The age- and sex-standardized incidence rate (ASR) (95% confidence interval [CI]) for overall malignancy of the SECURE cohort was 313.9/105 PY (271.4–361.3), and the standardized incidence rate ratio (SIR) (95% CI) was 0.745 (0.667–0.826). The ASR was decreased compared to the estimated incidence rate of malignancies in the Japanese general population (462.4/105 PY). The SIRs for site-specific nonhematopoietic malignancies of the SECURE cohort were not significantly elevated compared to the Japanese general population. A significant increase of SIR for malignant lymphoma (6.183, 95% CI, 4.809–7.643) was found in the SECURE cohort, similar to or slightly higher than the SIR previously reported from Japanese cohorts for RA patients.Conclusions: Continued vigilance with larger numbers of patients, longer observation periods, and inclusion of different biologics are recommended.

Pattern and frequency of endometrial changes and pathologies among pregnant and nonpregnant women presented with abnormal uterine bleeding in rural inhabitants of north India: A retrospective secondary data analysis

Background: Abnormal uterine bleeding i.e., dysfunctional uterine bleed is one of the most frequent problems that occur in women of all ages. It occurs due to various disorders. Endometrial biopsy remains a preferred sampling procedure for the diagnosis of endometrial pathology. This study was conducted to determine the type, frequency of endometrial pathologies in women presenting with AUB, and their association with different age groups. Materials and Methods: This was retrospective study conducted in Histopathology Section of the Pathology Department of the Rural Institute of Medical Science and Research, Saifai, Etawah. Five hundred and forty seven (547) patients who have undergone endometrial biopsies and who clinically presented with AUB were included in this study. The pattern of endometrial pathologies was diagnosed, classified, and it was compared in terms of age. Result: Out of the 563 patients who have undergone endometrial biopsies and who presented with AUB, 547 were included in study and others were discarded because of scanty tissue. The patients were aged between 15 years and 72 years, and most of the patients were aged between 41 years and 50 years (36.56%). The common clinical presentation was menorrhagia (42.96%). The most common pattern on histopathology was secretory endometrium (28.33%). Pregnancy related pathology was also forming a bulk (17.36%), whereas incidence rate of malignancy was low (1.09%). Conclusion: AUB is the common clinical complaint interfering with the quality of life in healthy women. Endometrial sampling therefore, biopsy or curettage, is an important diagnostic procedure for the evaluation of AUB with special preference above 35 years of age to rule out malignancy.

Spectrum of cancer in adolescents and young adult: An epidemiological and clinicopathological evaluation.

Changing scenario of cancer in adolescents and young adult (AYA) age group becomes an emerging and alarming problem. The age span that falls under the AYA umbrella, i.e., 15-29 years, is broad and having unique characteristic as compared to older and pediatric cohort. Only a few data are available in English literature about this age group where the spectrum of cancer varies accordingly as the function of age. The aim of this study was to evaluate the incidence and pattern of tumor in adolescents and young age group. A retrospective observational study was done at a tertiary care center. Medical records of patients aged 15-29 years registered from 2011 to 2015 were retrieved for analysis. Incidence rate of malignancy in AYA age is 5.71% in this observational study. Male:female ratio was 1.81:1. Most common cancer in this age group was head and neck cancer > central nervous system > gastrointestinal tract in the entire cohort. The malignancy spectrum, their subtypes, and demographic distribution in the AYA cohort have diversity among different cancer centers within India as well as in different countries across the world.

Cancer risk in relatives of patients with a primary disorder of lymphocyte cytotoxicity: a retrospective cohort study

Mutations in genes for perforin-dependent lymphocyte cytotoxicity are associated with haemophagocytic lymphohistiocytosis, a rare disease of severe hyperinflammation that typically becomes evident in early childhood. It has been suggested that individuals with hypomorphic biallelic mutations in genes associated with haemophagocytic lymphohistiocytosis are at increased risk of developing haematological malignancies. We aimed to assess whether relatives of patients with primary haemophagocytic lymphohistiocytosis (ie, heterozygous carriers of these mutated genes) were more likely to develop cancer. In this retrospective cohort study, we used a multigeneration registry to identify relatives (parents and grandparents) of 79 Swedish children (<15 years) with primary haemophagocytic lymphohistiocytosis diagnosed between 1971 and 2011. For each relative, we randomly selected eight matched individuals from the Swedish total population registry, stratified for sex, birth year, and birth region. Relatives and matched controls were cross-linked with the Swedish Cancer Registry to establish cancer incidence rate. We then calculated the incidence rate ratio between first-degree and second-degree relatives and the matched controls. Additionally, we assessed natural-killer-cell-mediated cytotoxicity in a subgroup of first-degree relatives using standard 4 h (51)Cr assay and flow cytometry quantification of the upregulation of surface CD107a. We identified 346 first-degree and second-degree relatives from 67 families (67 mothers, 66 fathers, 106 grandmothers, and 107 grandfathers) and 2768 matched controls. Median follow-up was 49 years, range 0-54 years. By death or last follow-up (Dec 31, 2012), first-degree relatives had a significantly increased incidence rate of malignancies than did controls (incidence rate per 1000 person-years 2.78 [95% CI 1.42-4.15] vs 1.56 [1.16-1.95]; incidence rate ratio 1.79 [95% CI 1.06-3.03]; p=0.030). Mothers had a particularly increased risk (incidence rate per 1000 person-years 4.43 [95% CI 1.99-6.87] vs 1.60 [1.08-2.11]; incidence rate ratio 2.78 [95% CI 1.48-5.21]; p=0.0014), whereas no difference was found between fathers and controls (1.24 [0.00-2.51] vs 1.52 [0.89-2.15]; 0.82 [0.29-2.29]; p=0.70) or between grandparents and controls (7.24 [5.44-9.04] vs 6.36 [5.70-7.03]; 1.14 [0.88-1.48]; p=0.33). Functional analysis of heterozygous carriers of mutations associated with haemophagocytic lymphohistiocytosis could not show significantly reduced lymphocyte cytotoxicity. Heterozygous mutations in genes associated with haemophagocytic lymphohistiocytosis might be a new risk factor for cancer. The increased risk of cancer might imply haploinsufficiency of cytotoxic lymphocyte-mediated immunosurveillance of cancer in carriers of these mutations. Our findings might support intensified screening for malignancies in relatives of patients with haemophagocytic lymphohistiocytosis. Swedish Children's Cancer Foundation, Swedish Research Council, Histiocytosis Association, Swedish Cancer Society, Swedish Cancer and Allergy Foundation, Mary Béve Foundation, Karolinska Institutet Research Foundation, Stockholm County Council (ALF-project).

Symptom and Comorbidity Burden in Chronic Disease: Comparison of HIV infection and Diabetes Mellitus in Aging Patients

Background: Data on the relative contribution of HIV-infection to aging and age-related diseases remains inconclusive, and the total burden of disease has not been compared to other chronic diseases associated with premature aging. The purpose of this study was to investigate aging with HIV-infection and to compare it to aging with diabetes mellitus (DM) type 2 and aging without severe chronic disease. Methods: This was a prospective multi-center cohort study evaluating differences in the total burden of disease between different groups of older patients (≥ 50 years). HIV-infected patients were compared to HIV-negative patients with DM type 2 and to a control group of patients without severe chronic disease. Physical constitution and activity, symptoms of aging, cardiovascular risk profile and comorbidities were analyzed. Clinical variables and patient questionnaires were assessed during 18 months follow-up. Results: Among 761 participants (255 HIV, 249 DM, and 257 controls), weakness was most frequently found in HIV-infected patients. The perceived severity of symptoms of aging was significantly higher in patients with HIVinfection or DM than in the control group. Several comorbidities such as renal, neurological and cardiovascular disorders were more common in patients with HIV-infection or DM than in the control group. After adjusting for smoking and non-modifiable risk factors, the prevalence odds of a high cardiovascular risk remained markedly increased for patients with DM and, to a lesser extent, also for patients with HIV-infection. Malignancy incidence rates were highest in HIV-infected patients, followed by patients with DM and lowest in the control group. Conclusions: This large cohort study in aging patients showed a considerable burden of disease associated with antiretrovirally treated HIV-infection as well as DM when compared to a control population without severe chronic disease – reflecting the need for specific prevention strategies and screening tools.

Breast and cervical cancer in patients with systemic lupus erythematosus

To study the incidence of tumors in a Brazilian sample of women with systemic lupus erythematosus. This is a retrospective study of 395 medical charts from women with systemic lupus erythematosus diagnosed by the presence of at least 4 of the American College of Rheumatology classification criteria for the diagnosis of this disease and followed for the last 10 years in a rheumatology outpatient clinic. Demographic data (age and ethnicity of patients), data on disease duration, use of immunomodulators and on the presence of neoplasms were listed. Results are presented in frequency and contingency tables. The incidence rate of malignancies in women with lupus was compared with that of the general population for the same demographic region for the past ten years, using data published by the Brazilian National Cancer Institute (INCA). Association studies were carried out by the Fisher and χ(2) tests, when the data were nominal, and by Mann-Whitney test, when numeric. The level of significance was set at 5%. Twenty-two cases of malignant tumors were identified during these 10 years of follow-up (22 cases/395 or 5.5% of the sample), being the most common those of the uterine cervix (10 cases/395 or 2.5% of the sample) and breast cancer (9 cases/395 or 2.2% of the sample). The presence of tumors was associated with disease duration (p=0.006) and was not influenced by treatment with methotrexate (p=0.1), azathioprine (p=0.9), cyclophosphamide (p=0.6) and glucocorticoids (p=0.3). Breast and uterine cervix tumors were more common in systemic lupus erythematosus women than in the general population (p<0.0001 for both). A high prevalence of malignant tumors was found in this sample, with tumors being more common in patients with longer disease duration. The most frequent tumors affected the breast and uterus at a higher incidence than in the general population. The presence of tumors was not influenced by the use of glucocorticoids or immunosuppressors.

Long-term safety of subcutaneous abatacept in rheumatoid arthritis: integrated analysis of clinical trial data representing more than four years of treatment.

ObjectiveTo investigate the safety of long-term subcutaneous (SC) abatacept treatment using integrated clinical trial data obtained in patients with rheumatoid arthritis refractory to traditional disease-modifying antirheumatic drugs.MethodsData from the double-blind and open-label phases of 5 clinical trials of SC abatacept were pooled. The overall and 6-month incidence rates were calculated as events per 100 patient-years of exposure.ResultsThis analysis included 1,879 patients with 4,214.6 patient-years of exposure to SC abatacept. The mean ± SD length of exposure was 27.3 ± 9.1 months. The reported incidence rate of serious infections was 1.79 (95% confidence interval [95% CI] 1.42–2.24); the most frequent infections were pneumonia (incidence rate 0.36 [95% CI 0.22–0.59]), urinary tract infection (incidence rate 0.14 [95% CI 0.06–0.32]), and gastroenteritis (incidence rate 0.10 [95% CI 0.04–0.25]). Tuberculosis occurred rarely (incidence rate 0.09 [95% CI 0.04–0.25]). The reported incidence rate of malignancies was 1.32 (95% CI 1.01–1.72), and the most common was solid organ malignancy (incidence rate 0.69 [95% CI 0.48–0.99]). The incidence rate of autoimmune events was 1.37 (95% CI 1.06–1.78), and the most frequent events were psoriasis (incidence rate 0.33 [95% CI 0.20–0.56]) and Sjögren's syndrome (incidence rate 0.24 [95% CI 0.13–0.44]). The reported incidence rate of local injection site reactions was 1.72 (95% CI 1.36–2.17); these events occurred primarily during the first 6 months of treatment, and almost all were of mild or moderate intensity. The incidence rates of serious infections, malignancies, autoimmune events, and injection site reactions did not increase over time.ConclusionLong-term treatment with SC abatacept was associated with low incidence rates of serious infections, malignancies, and autoimmune events and was well tolerated, with infrequent injection site reactions. These findings are consistent with those related to treatment with intravenous abatacept. Long-term treatment with SC abatacept did not lead to new safety signals over time.

SAT0096 Safety of TNF Inhibitors and Predictors of Its Discontinuation in Elderly Patients with Rheumatoid Arthritis

BackgroundThe concerns about development of adverse events (AEs) in elderly RA patients as a result of age-related changes in drug metabolism and the presence of comorbid illnesses are emphasizing due...

A Comparison of the Malignancy Incidence Among Patients With Psoriatic Arthritis and Patients With Rheumatoid Arthritis in a Large US Cohort

ObjectiveTo compare the incidence rates of malignancy among patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) in the Consortium of Rheumatology Researchers of North America (CORRONA) registry.MethodsWe analyzed 2,970 patients with PsA (7,133 patient‐years of followup) and 19,260 patients with RA (53,864 patient‐years of followup). Using a standardized adjudication process, we identified 40 confirmed malignancies in the patients with PsA and 307 confirmed malignancies in those with RA. Incidence rates were calculated per 100 patient‐years. Incidence rate ratios were estimated, with adjustment for age, sex, disease duration, body mass index, disease activity, year of enrollment, and medication use.ResultsThe overall malignancy incidence per 100 patient‐years was similar between patients with PsA and patients with RA (0.56 [95% confidence interval (95% CI) 0.40−0.76] and 0.56 [95% CI 0.50−0.63], respectively). Nonmelanoma skin cancer was the most common type of cancer in the overall cohort, with an incidence rate of 0.21 (95% CI 0.12−0.35) in PsA, and 0.20 (95% CI 0.17−0.24) in RA, with a calculated incidence rate ratio of 1.05 (95% CI 0.61−1.80; P = 0.85). Lymphoma rates were similar in PsA and RA (0.04 [95% CI 0.01−0.12] and 0.04 [95% CI 0.02−0.06], respectively; incidence rate ratio 1.00 [95% CI 0.17−3.11]; P = 0.67). The adjusted incidence rate ratio of malignancy in PsA versus RA was 1.17 (95% CI 0.82−1.69; P = 0.37).ConclusionThe incidence rates across malignancy subtypes were similar in the PsA and RA cohorts from a US registry.

Incidence rates of malignancies and hospitalized infectious events in patients with psoriasis with or without treatment and a general population in the U.S.A.: 2005–09

Rates of malignancies and hospitalized infectious events (HIEs) among psoriasis patients are higher than in the general population, but it is unclear if higher rates are associated with the underlying inflammatory state, treatments or both. To assess the incidence of malignancies and HIEs in a healthy US population, a psoriasis population, and four treated psoriasis populations. Using a US claims database, we identified a general population, a psoriasis cohort, and four treatment cohorts [non-biologic systemics, etanercept, other TNF blockers (adalimumab, infliximab) and phototherapy] to assess the incidence of lymphomas, nonmelanoma skin cancer (NMSC), all malignancies (excluding NMSC), and HIEs, standardized for age and sex. Among 40 987 patients with psoriasis, 11% were prescribed non-biologics, 15% etanercept, 6% other TNF blockers and 11% phototherapy. For all cancers, the psoriasis population rate (114/10 000 person-years) was 20% greater than the rate found in the general population (95/10 000 person-years). For NMSC, the psoriasis population rate (129/10 000 person-years) was 65% greater than the general population rate (78/10 000 person-years). The incidence rate for each treatment modality was lower than the overall psoriasis cohort, except for phototherapy. There was little difference in the rates of lymphomas. NMSC rates were higher among patients treated with phototherapy. HIE rates ranged from 165/10 000 person-years for the phototherapy group to 262/10 000 person-years for the other anti-TNF group. Patients with psoriasis appear to have higher rates of malignancy and HIE than the general population, with little difference in rates between the treatment methods, except for a higher rate of cancer among those receiving phototherapy.