[Show abstract][Hide abstract] ABSTRACT: To examine the association of serum lipids, inflammation and seropositivity on coronary heart disease (CHD) and stroke in patients with rheumatoid arthritis (RA).
The incidence of hospitalised myocardial infarction (MI) or stroke was calculated in a cohort of patients with RA receiving care within the national Veterans Health Administration from 1998 to 2011. Cox proportional hazard models were used to examine the association between these outcomes and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as time-varying variables, divided into quintiles.
There were 37 568 patients with RA in the cohort with mean age of 63 years (SD 12.1); 90% were men. There was a no clear association between LDL-C and CHD/stroke. Compared with lower HDL-C (<34 mg/dL), higher HDL-C (≥54 mg/dL) was inversely associated with MI (hazard ratio (HR)=0.68, 95% CI 0.55 to 0.85) and stroke (HR=0.69, 95% CI 0.50 to 0.96). Higher CRP >2.17 mg/dL (vs CRP <0.26 mg/dL) was associated with increased risk (HR=2.43, 95% CI 1.77 to 3.33) for MI and 2.02 (95% CI 1.32 to 3.08) for stroke. ESR >47 mm/h compared with <8 mm/h had an HR 1.87 (95% CI 1.39 to 2.52) for MI and 2.00 (95% CI 1.26 to 3.18) for stroke. The association between MI was significant for RA seropositivity (HR=1.23, 95% CI 1.03 to 1.48).
In this predominantly older male RA cohort, there was no clear association between LDL-C and CHD, whereas higher HDL-C was inversely associated with MI and stroke. CRP and ESR were similarly associated with increase MI risk and stroke, reflecting the prominent role of inflammation in CHD risk in RA.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Annals of the Rheumatic Diseases 01/2015; DOI:10.1136/annrheumdis-2013-204987 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Risks of hospitalized infections associated with newer biologic agents have not been well characterized in relation to risks with anti-TNF therapy, especially in rheumatoid arthritis (RA) patients with high comorbidity burdens.
Objectives To compare the risk of hospitalized infections among RA patients switching from anti-TNF therapy to rituximab (RTX), abatacept (ABA) or another anti-TNF.
Methods Using data from 2002-10 from the U.S. Veteran’s Health Administration, we identified a cohort of 38453 RA patients. Eligible patients started RTX, ABA, or anti-TNF therapy after prior exposure to another anti-TNF agent. To minimize confounding from channeling of cancer patients to certain biologics, patients with a history of cancer were excluded to form 2 cohorts: Exclusion for any type of prior cancer using all available data (3257 episodes, 2559 patients) or exclusion only for hematologic cancer in the prior 12 months (3848 episodes, 3018 patients). Baseline characteristics defined in 1 year prior to treatment initiation. Exposure was as-treated based upon days supply (injections) or usual dosing intervals (infusions), with 12 months assumed for RTX exposure. Current exposure was extended by 90 days for all biologics. The outcome was hospitalization with primary diagnosis code for bacterial infection. The hazard ratio (HR, 95% CI) for infection for RTX and ABA vs. anti-TNFs was calculated, adjusting for multiple potential confounders.
Results 523 RTX, 366 ABA and 2959 anti-TNF switcher episodes were identified in RA patients without hematologic cancers; 15% of treatment episodes were further excluded with the more restrictive cancer exclusion to form a 2nd cohort. This cohort’s mean overall age was 60.8±10.7 years, 87% male, 25% diabetes, 15% COPD, 3% heart failure, and 66% used glucocorticoids. 2/3rd of the anti-TNF exposure was adalimumab. The most common types of hospitalized infections were pneumonia (36%), skin/soft tissue infections (26%), gastroenteritis (7%) and urinary tract infections (6%). In the less restrictive RA cohort, crude hospitalized infection rates/100person years were RTX: 15.9, ABA: 10.2 and anti-TNF: 12.7. In the less restrictive RA cohort, adjusted HRs for infection were comparable to or lower than for anti-TNF therapy: RTX: 0.85 (0.62-1.12) and ABA: 0.72 (0.50-1.10). In the more restrictive RA cohort, results were similar: adjusted HR for RTX: 0.76 (0.50-1.15) and ABA: 0.58 (0.36-0.93) compared to anti-TNF therapy. Multiple comorbidities and medications were associated with infections (diabetes HR=1.4, 95% CI 1.1-1.7; chronic lung disease HR=1.5, 1.1–1.9; prednisone >7.5mg/day HR=2.1, 1.6-2.7).
Conclusions In older, predominantly male, US veterans with RA and high comorbidities, risks of hospitalized bacterial infections for patients treated with RTX or ABA were comparable to or lower than for patients switching to a different anti-TNF therapy (mostly ADA). Ongoing work is characterizing the comparative risks of opportunistic infections.
Disclosure of Interest J. Curtis Consultant for: Roche/Genetech, UCB, Centocor CORRONA, Amgen, Pfizer, BMS, Crescendo, Abbott, S. Yang: None Declared, N. Patkar: None Declared, L. Chen: None Declared, J. Singh Grant/Research support from: Takeda, Savient, Consultant for: URL pharmaceuticals, Takeda, Ardea, Savient, Allergan, Novartis, G. Cannon: None Declared, T. Mikuls: None Declared, E. Delzell Grant/Research support from: Amgen, K. Saag Consultant for: Amgen; Lilly; Merck; Novartis; Savient; Ardea; Regeneron; URL, Abbott; DSMB – BioCryst; Roche; Lilly, M. Safford: None Declared, S. Duvall Grant/Research support from: Anolinx, LLC, Genentech, Roche, Amgen, Shire, K. Alexander Employee of: Genetech, P. Napalkov Employee of: Genetech, A. Kamauu Employee of: President- Anolinx LLC, J. Baddley Consultant for: Abbott, Merck
Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):361-361. DOI:10.1136/annrheumdis-2012-eular.2606 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare incidence rates of selected opportunistic infections among children with and children without juvenile idiopathic arthritis (JIA).
Using US national Medicaid administrative claims data from 2000 through 2005, we identified a cohort of children with JIA based on physician diagnosis codes and dispensed medications. We also identified a non-JIA comparator cohort of children diagnosed as having attention deficit hyperactivity disorder (ADHD). We defined 15 types of opportunistic infection using physician diagnosis or hospital discharge codes; criteria for 7 of these types also included evidence of treatment with specific antimicrobial agents. We calculated infection incidence rates. The rates in the ADHD comparator cohort were standardized to the age, sex, and race distribution of the JIA cohort. We calculated incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) to compare infection rates.
The JIA cohort included 8,503 children with 13,990 person-years of followup. The ADHD comparator cohort included 360,362 children with 477,050 person-years of followup. When all opportunistic infections were considered together as a single outcome, there were 42 infections in the JIA cohort (incidence rate 300 per 100,000 person-years; IRR 2.4 [95% CI 1.7–3.3] versus ADHD). The most common opportunistic infections among children with JIA were 3 cases of Coccidioides (incidence rate 21 per 100,000 person-years; IRR 101 [95% CI 8.1–5,319] versus ADHD), 5 cases of Salmonella (incidence rate 35 per 100,000 person-years; IRR 3.8 [95% CI 1.2–9.5]), and 32 cases of herpes zoster (incidence rate 225 per 100,000 person-years; IRR 2.1 [95% CI 1.4–3.0]).
Opportunistic infections are rare among children with JIA. Nevertheless, children with JIA had a higher rate of opportunistic infections, including an increased rate of Coccidioides, Salmonella, and herpes zoster compared to children with ADHD.
[Show abstract][Hide abstract] ABSTRACT: To determine among patients with autoimmune diseases in the USA whether the risk of non-viral opportunistic infections (OI) was increased among new users of tumour necrosis factor α inhibitors (TNFI), when compared to users of non-biological agents used for active disease.
We identified new users of TNFI among cohorts of rheumatoid arthritis (RA), inflammatory bowel disease and psoriasis-psoriatic arthritis-ankylosing spondylitis patients during 1998-2007 using combined data from Kaiser Permanente Northern California, two pharmaceutical assistance programmes for the elderly, Tennessee Medicaid and US Medicaid/Medicare programmes. We compared incidence of non-viral OI among new TNFI users and patients initiating non-biological disease-modifying antirheumatic drugs (DMARD) overall and within each disease cohort. Cox regression models were used to compare propensity-score and steroid- adjusted OI incidence between new TNFI and non-biological DMARD users.
Within a cohort of 33 324 new TNFI users we identified 80 non-viral OI, the most common of which was pneumocystosis (n=16). In the combined cohort, crude rates of non-viral OI among new users of TNFI compared to those initiating non-biological DMARD was 2.7 versus 1.7 per 1000-person-years (aHR 1.6, 95% CI 1.0 to 2.6). Baseline corticosteroid use was associated with non-viral OI (aHR 2.5, 95% CI 1.5 to 4.0). In the RA cohort, rates of non-viral OI among new users of infliximab were higher when compared to patients newly starting non-biological DMARD (aHR 2.6, 95% CI 1.2 to 5.6) or new etanercept users (aHR 2.9, 95% CI 1.5 to 5.4).
In the USA, the rate of non-viral OI was higher among new users of TNFI with autoimmune diseases compared to non-biological DMARD users.
Annals of the rheumatic diseases 07/2013; 73(11). DOI:10.1136/annrheumdis-2013-203407 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Herpes zoster reactivation disproportionately affects patients with rheumatoid arthritis (RA). It is unclear whether anti-tumor necrosis factor (anti-TNF) therapy elevates herpes zoster risk.
To ascertain whether initiation of anti-TNF therapy compared with nonbiologic comparators is associated with increased herpes zoster risk.
We identified new users of anti-TNF therapy among cohorts of patients with RA, inflammatory bowel disease, and psoriasis, psoriatic arthritis, or ankylosing spondylitis from 1998 through 2007 within a large US multi-institutional collaboration combining data from Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the Elderly, Tennessee Medicaid, and national Medicaid/Medicare programs. We compared herpes zoster incidence between new anti-TNF users (n=33,324) and patients initiating nonbiologic disease-modifying antirheumatic drugs (DMARDs) (n=25,742) within each inflammatory disease cohort (last participant follow-up December 31, 2007). Within these cohorts, we used Cox regression models to compare propensity score-adjusted herpes zoster incidence between new anti-TNF and nonbiologic DMARD users while controlling for baseline corticosteroid use.
Incidence of herpes zoster cases occurring after initiation of new anti-TNF or nonbiologic DMARD therapy.
Among 33,324 new users of anti-TNF therapy, we identified 310 herpes zoster cases. Crude incidence rates among anti-TNF users were 12.1 per 1000 patient-years (95% CI, 10.7-13.6) for RA, 11.3 per 1000 patient-years (95% CI, 7.7-16.7) for inflammatory bowel disease, and 4.4 per 1000 patient-years (95% CI, 2.8-7.0) for psoriasis, psoriatic arthritis, or ankylosing spondylitis. Baseline use of corticosteroids of 10 mg/d or greater among all disease indications was associated with elevated risk (adjusted hazard ratio [HR], 2.13 [95% CI, 1.64-2.75]) compared with no baseline use. For patients with RA, adjusted incidence rates were similar between anti-TNF and nonbiologic DMARD initiators (adjusted HR, 1.00 [95% CI, 0.77-1.29]) and comparable between all 3 anti-TNF therapies studied. Across all disease indications, the adjusted HR was 1.09 (95% CI, 0.88-1.36). CONCLUSION AND RELEVANCE: Among patients with RA and other inflammatory diseases, those who initiated anti-TNF therapies were not at higher risk of herpes zoster compared with patients who initiated nonbiologic treatment regimens.
JAMA The Journal of the American Medical Association 03/2013; 309(9):887-95. DOI:10.1001/jama.2013.1099 · 30.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: To evaluate the incidence of optic neuritis (ON) in patients using anti-tumor necrosis factor (TNF) alpha therapy. DESIGN: Retrospective, population-based cohort study. METHODS: We identified new users of anti-TNF therapy (etanercept, infliximab, or adalimumab) or nonbiologic disease-modifying antirheumatic drugs (DMARDs) during 2000-2007 from the following data sources: Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the Elderly, Tennessee Medicaid, and National Medicaid/Medicare. Within this cohort, we used validated algorithms to identify ON cases occurring after onset of new drug exposure. We then calculated and compared ON incidence rates between exposure groups. RESULTS: We identified 61 227 eligible inflammatory disease patients with either new anti-TNF or new nonbiologic DMARD use. Among this cohort, we found 3 ON cases among anti-TNF new users, occurring a median of 123 days (range, 37-221 days) after anti-TNF start. The crude incidence rate of ON across all disease indications among anti-TNF new users was 10.4 (95% CI 3.3-32.2) cases per 100 000 person-years. In a sensitivity analysis considering current or past anti-TNF or DMARD use, we identified a total of 6 ON cases: 3 among anti-TNF users and 3 among DMARD users. Crude ON rates were similar among anti-TNF and DMARD groups: 4.5 (95% CI 1.4-13.8) and 5.4 (95% CI 1.7-16.6) per 100 000 person-years, respectively. CONCLUSION: Optic neuritis is rare among those who initiate anti-TNF therapy and occurs with similar frequency among those with nonbiologic DMARD exposure.
American Journal of Ophthalmology 09/2012; 155(1). DOI:10.1016/j.ajo.2012.06.023 · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the incidence of hospitalized bacterial infections among children with and children without juvenile idiopathic arthritis (JIA) and to examine the effects of selected medications.
Using national Medicaid data from 2000 through 2005, we identified a cohort of children with JIA and a comparator cohort of children with attention deficit hyperactivity disorder (ADHD). Exposures to methotrexate (MTX), TNF inhibitors, and oral glucocorticoids (GCs) were determined using pharmacy claims. Patients hospitalized with bacterial infections were identified using coded discharge diagnoses. We calculated adjusted hazard ratios (HR(adj) ) to compare infection incidence rates while adjusting for relevant covariates.
We identified 8,479 JIA patients with 13,003 person-years of followup; 36% took MTX and 16% took TNF inhibitors. Compared with ADHD patients, JIA patients who were not currently taking MTX or TNF inhibitors had an increased rate of infection (HR(adj) 2.0 [95% confidence interval (95% CI) 1.5, 2.5]). Among JIA patients not receiving TNF inhibitor therapy, MTX users had a similar rate of infection as those not currently taking MTX (HR(adj) 1.2 [95% CI 0.9, 1.7]). TNF inhibitor use (irrespective of MTX) resulted in a similar rate of infection as use of MTX without a TNF inhibitor (HR(adj) 1.2 [95% CI 0.8, 1.8]). Use of high-dose GCs (≥10 mg/day of prednisone or equivalent) increased the rate of infection as compared with no GC use, after adjustment for MTX and TNF inhibitor use (HR(adj) 3.1 [95% CI 2.0, 4.7]).
Children with JIA had an increased rate of infection compared to children with ADHD. Among children with JIA, the rate of infection was not increased with MTX or TNF inhibitor use, but was significantly increased with high-dose GC use.
[Show abstract][Hide abstract] ABSTRACT: Figure 2. 2012 American College of Rheumatology (ACR) recommendations update for the treatment of established rheumatoid arthritis (RA), defined as a disease duration ≥6 months or meeting the 1987 ACR classification criteria. Depending on a patient's current medication regimen, the management algorithm may begin at an appropriate rectangle in the figure, rather than only at the top of the figure. Disease-modifying antirheumatic drugs (DMARDs) include hydroxychloroquine (HCQ), leflunomide (LEF), methotrexate (MTX), minocycline, and sulfasalazine (therapies are listed alphabetically; azathioprine and cyclosporine were considered but not included). DMARD monotherapy refers to treatment in most instances with HCQ, LEF, MTX, or sulfasalazine; in few instances, where appropriate, minocycline may also be used. Anti–tumor necrosis factor (anti-TNF) biologics include adalimumab, certolizumab pegol, etanercept, infliximab, and golimumab. Non-TNF biologics include abatacept, rituximab, or tocilizumab (therapies are listed alphabetically). For the level of evidence supporting each recommendation, please see Supplementary Appendix 7 (available in the online version of this article at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2151-4658).* Definitions of disease activity are discussed in Tables 2 and 3 and Supplementary Appendix 4 (available in the online version of this article at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2151-4658) and were categorized as low, moderate, or high.† Features of poor prognosis included the presence of 1 or more of the following: functional limitation (e.g., Health Assessment Questionnaire score or similar valid tools), extraarticular disease (e.g., presence of rheumatoid nodules, RA vasculitis, Felty's syndrome), positive rheumatoid factor or anti–cyclic citrullinated peptide antibodies (33–37), and bony erosions by radiograph (38).‡ Combination DMARD therapy with 2 DMARDs, which is most commonly MTX based, with few exceptions (e.g., MTX + HCQ, MTX + LEF, MTX + sulfasalazine, sulfasalazine + HCQ), and triple therapy (MTX + HCQ + sulfasalazine).§ Reassess after 3 months and proceed with escalating therapy if moderate or high disease activity in all instances except after treatment with a non-TNF biologic (rectangle D), where reassessment is recommended at 6 months due to a longer anticipated time for peak effect.¶ LEF can be added in patients with low disease activity after 3–6 months of minocycline, HCQ, MTX, or sulfasalazine.# If after 3 months of intensified DMARD combination therapy or after a second DMARD has failed, the option is to add or switch to an anti-TNF biologic.** Serious adverse events were defined per the US Food and Drug Administration (FDA; see below); all other adverse events were considered nonserious adverse events.†† Reassessment after treatment with a non-TNF biologic is recommended at 6 months due to anticipation that a longer time to peak effect is needed for non-TNF compared to anti-TNF biologics.‡‡ Any adverse event was defined as per the US FDA as any undesirable experience associated with the use of a medical product in a patient. The FDA definition of serious adverse event includes death, life-threatening event, initial or prolonged hospitalization, disability, congenital anomaly, or an adverse event requiring intervention to prevent permanent impairment or damage.Download figure to PowerPoint
[Show abstract][Hide abstract] ABSTRACT: To ascertain the incidence of progressive multifocal leukoencephalopathy (PML) in patients with selected rheumatic diseases, to describe the characteristics of PML cases occurring in this setting, and to evaluate the extent to which such cases occurred in the context of biologic therapies such as rituximab or tumor necrosis factor antagonists.
We conducted a large population-based study to describe the incidence and risk factors for PML among patients with rheumatoid arthritis, psoriatic arthritis, psoriasis, juvenile idiopathic arthritis, inflammatory bowel disease, and ankylosing spondylitis using national inpatient and outpatient administrative data from the entire Center for Medicare and Medicaid Services from 2000-2009. Suspected PML cases were identified using hospital discharge diagnosis codes. Risk factors for PML were evaluated using outpatient data ≥6 months prior to PML diagnosis.
Among 2,030,578 patients with autoimmune diseases of interest, a total of 53 PML cases were identified (2.6 per 100,000 patients). Most PML cases had human immunodeficiency virus (HIV) and/or cancer. Nine PML cases had evidence for biologic use prior to PML hospitalization, of which 3 had neither HIV nor malignancy and were exposed to biologics within 12 (rituximab) or 6 months (all other biologics) prior to PML diagnosis. PML occurred at an estimated incidence of 0.2 per 100,000 patients with autoimmune diseases who did not have HIV or malignancy.
PML occurs at a very low incidence among patients with rheumatic diseases but can occur even in the absence of HIV or malignancy.
[Show abstract][Hide abstract] ABSTRACT: Administrative claims databases have large samples and high generalizability. They have been used to evaluate associations of atypical femoral fractures with bisphosphonates. We developed and assessed accuracy of claims-based algorithms with hospital and physician diagnosis codes for these fractures. Medical records and radiology reports of all adults admitted at University of Alabama at Birmingham Health System from 2004 to 2008 with International Classification of Diseases, Ninth Revision hospital discharges and surgeons' fracture repair codes for subtrochanteric femoral fractures and random sample of other femoral fractures were reviewed. We identified 137 persons with suspected subtrochanteric femoral fractures and randomly selected 50 persons with either suspected diaphyseal femoral fractures or hip fractures other than subtrochanteric and diaphyseal femoral fractures (typical hip fractures). Eleven patients had radiographic features indicative of atypical femoral fractures. The positive predictive value (PPV) of claims-based algorithms varied with primary or secondary positions on discharge diagnoses and the sources of diagnosis codes. The PPV for fractures ranged 69-89% for subtrochanteric femoral, 89-98% for diaphyseal femoral, and 85-98% for typical hip fractures. The PPV of administrative codes for defining a femoral fracture as atypical was low and imprecise. Claims-based algorithms combining hospital discharges with surgeon's diagnosis codes had high PPV to identify the site of subtrochanteric or diaphyseal femoral fractures vs typical hip fractures. However, claims-based data were not accurate in identifying atypical femoral fractures. These claims algorithms will be useful in future population-based observational studies to evaluate associations between osteoporosis medications and subtrochanteric and diaphyseal femoral fractures.
[Show abstract][Hide abstract] ABSTRACT: Although tumor necrosis factor (TNF)-α antagonists are increasingly used in place of nonbiologic comparator medications, their safety profile remains incomplete.
To determine whether initiation of TNF-α antagonists compared with nonbiologic comparators is associated with an increased risk of serious infections requiring hospitalization.
Within a US multi-institutional collaboration, we assembled retrospective cohorts (1998-2007) of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis, or ankylosing spondylitis (psoriasis and spondyloarthropathies) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid, and national Medicaid/Medicare. TNF-α antagonists and nonbiologic regimens were compared in disease-specific propensity score (PS)-matched cohorts using Cox regression models with nonbiologics as the reference. Baseline glucocorticoid use was evaluated as a separate covariate.
Infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-α antagonists or nonbiologic regimens.
Study cohorts included 10,484 RA, 2323 IBD, and 3215 psoriasis and spondyloarthropathies matched pairs using TNF-α antagonists and comparator medications. Overall, we identified 1172 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. Among patients with RA, serious infection hospitalization rates were 8.16 (TNF-α antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR], 1.05 [95% CI, 0.91-1.21]). Among patients with IBD, rates were 10.91 (TNF-α antagonists) and 9.60 (comparator) per 100 person-years (aHR, 1.10 [95% CI, 0.83-1.46]). Among patients with psoriasis and spondyloarthropathies, rates were 5.41 (TNF-α antagonists) and 5.37 (comparator) per 100 person-years (aHR, 1.05 [95% CI, 0.76-1.45]). Among patients with RA, infliximab was associated with a significant increase in serious infections compared with etanercept (aHR, 1.26 [95% CI, 1.07-1.47]) and adalimumab (aHR, 1.23 [95% CI, 1.02-1.48]). Baseline glucocorticoid use was associated with a dose-dependent increase in infections.
Among patients with autoimmune diseases, compared with treatment with nonbiologic regimens, initiation of TNF-α antagonists was not associated with an increased risk of hospitalizations for serious infections.
JAMA The Journal of the American Medical Association 11/2011; 306(21):2331-9. DOI:10.1001/jama.2011.1692 · 30.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although biologic treatments have excellent efficacy for many autoimmune diseases, safety concerns persist. Understanding the absolute and comparative risks of adverse events in patient and disease subpopulations is critical for optimal prescribing of biologics.
The Safety Assessment of Biologic Therapy collaborative was federally funded to provide robust estimates of rates and relative risks of adverse events among biologics users using data from national Medicaid and Medicare plus Medicaid dual-eligible programs, Tennessee Medicaid, Kaiser Permanente, and state pharmaceutical assistance programs supplementing New Jersey and Pennsylvania Medicare programs. This report describes the organizational structure of the collaborative and the study population and methods.
This retrospective cohort study (1998-2007) examined risks of seven classes of adverse events in relation to biologic treatments prescribed for seven autoimmune diseases. Propensity scores were used to control for confounding and enabled pooling of individual-level data across data systems while concealing personal health information. Cox proportional hazard modeling was used to analyze study hypotheses.
The cohort was composed of 159,000 subjects with rheumatic diseases, 33,000 with psoriasis, and 46,000 with inflammatory bowel disease. This report summarizes demographic characteristics and drug exposures. Separate reports will provide outcome definitions and estimated hazard ratios for adverse events.
This comprehensive research will improve understanding of the safety of these treatments. The methods described may be useful to others planning similar evaluations.
Pharmacoepidemiology and Drug Safety 11/2011; 20(11):1199-209. DOI:10.1002/pds.2196 · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Newer biologic therapies such as TNF-alpha inhibitors represent important treatment advances for inflammatory and autoimmune diseases; however, risk of opportunistic infections (OIs) other than mycobacterial disease has been poorly characterized.
Methods: We identified new users of anti-TNF therapy from a cohort of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from 2000-2007 from Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the Elderly, Tennessee Medicaid and national Medicaid/Medicare. Cases of non-mycobacterial OIs were identified by use of ICD-9 codes and OI rates were estimated among initiators of TNF-alpha inhibitors and initiators of methotrexate or other non-biologic immunosuppressive agents (e.g. azathioprine, sulfasalazine). Follow-up was truncated at exposure discontinuation, death, study end or OI, whichever came first. The rate of OIs was compared between anti-TNF users and non-biologic comparator drugs in disease specific cohorts. Confounding was controlled through adjustment for the quintile of the propensity score and steroid use with Cox proportional hazards models.
Results: We identified 47235 new episodes of anti-TNF use among patients with inflammatory diseases. Among RA patients, the crude rate of non-mycobacterial, non-zoster OIs in new anti-TNF users was 236 per 100,000 person-years (adjusted hazard ratio 1.47; 95% CI: 0.73-3.3). Lower rates were seen in new anti-TNF users with PsO, PsA and AS (pooled rate, 121 per 100,000) and IBD (rate, 172 per 100,000). The crude rate of zoster in new anti-TNF users with RA was 541 per 100,000 person-years (adjusted hazard ratio 1.16; 95% CI: 0.77-1.8) and lower in patients with PsO, PsA and AS (pooled rate, 145 per 100,000) and IBD (rate, 129 per 100,000).
Conclusion: In a cohort of US patients with inflammatory diseases, overall rates for non-mycobacterial OIs are low and not significantly higher in new users of TNF drugs when compared to non-biologic comparators. Among new anti-TNF users, OI rates were lowest in patients with non-RA inflammatory diseases.
Infectious Diseases Society of America 2011 Annual Meeting; 10/2011
[Show abstract][Hide abstract] ABSTRACT: Background: Cryptococcosis (crypto) is an opportunistic fungal infection caused by C. neoformans and the emerging species C. gattii. Incidence and risk factor data for cryptococcosis in older Americans are limited.
Methods: We evaluated a 5% sample of national Medicare data for years 1999-2008 to determine incidence and risk factors for crypto. Cases were identified by ICD-9 code 117.5 and required one inpatient claim or at least two outpatient claims at least 7 days apart but within 90 days. Co-morbidities were identified by ICD-9 codes and defined as one physician claim within 6-months prior to the case date. We calculated national, regional and state-based incidence rates (per 100,000 person-years). Multivariable Poisson regression was used to determine risk factors for crypto.
Results: One hundred ninety-four cases of crypto were identified from a sample of 1,913,294 Medicare patients 65-years-of age or older. Mean age among cases was 79.6 years, 55.4% were male and 80.8% white. Ninety-day mortality among cases was 36.3%. Overall US incidence rate was 1.83/100,000 p-years and greatest in the South (2.65) and Western (1.75) regions. Incidence was highest in Arkansas (8.3) and Arizona (5.1). National and regional IR decreased during the study period (US 2.23 in 2000 to 1.09 in 2008). Multivariable regression analyses identified neutropenia (IRR 4.6), rheumatologic disease (IRR 2.6), chronic liver disease (IRR 2.4), chronic kidney disease (IRR 2.2), malignancy (IRR 2.2), COPD (IRR 2.2), diabetes (IRR 2.0), South region (IRR 2.6) and Western region (IRR 1.7) when compared to North; black race (IRR 1.6) and male gender (IRR 1.4) as significant risk factors for cryptococcosis.
Conclusion: Cryptococcosis is an uncommon infection in older Americans. Geographic variation in crypto IR was evident, with South and Western regions having increased incidence. As older Americans continue to comprise a greater proportion of the US population, identification of risk factors for cryptococcosis may aid surveillance and prevention strategies. Despite the reported emergence of C. gattii in some parts of the country, overall crypto incidence decreased during the study period.
Infectious Diseases Society of America 2011 Annual Meeting; 10/2011
[Show abstract][Hide abstract] ABSTRACT: Administrative claims data have not commonly been used to study the clinical effectiveness of medications for rheumatoid arthritis (RA) because of the lack of a validated algorithm for this outcome. We created and tested a claims-based algorithm to serve as a proxy for the clinical effectiveness of RA medications.
We linked Veterans Health Administration (VHA) medical and pharmacy claims for RA patients participating in the longitudinal Department of Veterans Affairs (VA) RA registry (VARA). Among individuals for whom treatment with a new biologic agent or nonbiologic disease-modifying agent in rheumatic disease (DMARD) was being initiated and with registry follow-up at 1 year, VARA and administrative data were used to create a gold standard for the claims-based effectiveness algorithm. The gold standard outcome was low disease activity (LDA) (Disease Activity Score using 28 joint counts (DAS28) ≤ 3.2) or improvement in DAS28 by > 1.2 units at 12 ± 2 months, with high adherence to therapy. The claims-based effectiveness algorithm incorporated biologic dose escalation or switching, addition of new disease-modifying agents, increase in oral glucocorticoid use and dose as well as parenteral glucocorticoid injections.
Among 1,397 patients, we identified 305 eligible biologic or DMARD treatment episodes in 269 unique individuals. The patients were primarily men (94%) with a mean (± SD) age of 62 ± 10 years. At 1 year, 27% of treatment episodes achieved the effectiveness gold standard. The performance characteristics of the effectiveness algorithm were as follows: positive predictive value, 76% (95% confidence interval (95% CI) = 71% to 81%); negative predictive value, 90% (95% CI = 88% to 92%); sensitivity, 72% (95% CI = 67% to 77%); and specificity, 91% (95% CI = 89% to 93%).
Administrative claims data may be useful in evaluating the effectiveness of medications for RA. Further validation of this effectiveness algorithm will be useful in assessing its generalizability and performance in other populations.
[Show abstract][Hide abstract] ABSTRACT: To investigate the epidemiology and geographic distribution of histoplasmosis, coccidioidomycosis, and blastomycosis in older persons in the United States, we evaluated a random 5% sample of national Medicare data from 1999 through 2008. We calculated national, regional, and state-based incidence rates and determined 90-day postdiagnosis mortality rates. We identified 776 cases (357 histoplasmosis, 345 coccidioidomycosis, 74 blastomycosis). Patient mean age was 75.7 years; 55% were male. Histoplasmosis and blastomycosis incidence was highest in the Midwest (6.1 and 1.0 cases/100,000 person-years, respectively); coccidioidomycosis incidence rate was highest in the West (15.2). On the basis of available data, for 86 (11.1%) cases, there was no patient exposure to a traditional disease-endemic area. Knowledge of areas where endemic mycosis incidence is increased may affect diagnostic or prevention measures for older adults at risk.
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis is a leading health problem worldwide due to the morbidity and mortality associated with fractures. However, a large number of fractures occur in persons without osteoporosis, when defined by bone mineral density alone. Numerous studies have shown that the risk of subsequent fracture is increased following fractures at most sites, and the increased risk is not limited to prior hip and vertebral fractures only. In addition, the amount of trauma present at the time of a fracture event appears to have limited impact on future fracture risk. Thus, even fractures that occur in the presence of high trauma should be recognized as evidence of possible bone fragility. Further methods to better identify persons at risk of future fracture are needed, such as through evaluation of other indicators of bone strength or recognition of modifiable, non-bone factors. Any initial fracture event is important for patients and caregivers to recognize as an implication for future fracture risk.
Current Osteoporosis Reports 06/2011; 9(3):122-8. DOI:10.1007/s11914-011-0064-1
[Show abstract][Hide abstract] ABSTRACT: Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient's individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.