Short-term costs associated with non-medical switching in autoimmune conditions.

OBJECTIVES: To estimate short-term costs associated with non-medical switch (NMS) from originator biologics to biosimilars among stable patients with autoimmune conditions in rheumatology, gastroenterology, and dermatology from a US provider's and third-party payer's perspective. METHODS: An economic model was constructed to estimate switching costs related to physician time and healthcare resource utilisation (HRU) at the initial NMS visit and over 3 months. The proportion of patients with relevant conditions treated with originators and expected NMS rate, physician time, HRU, and payer reimbursement were derived from a physician survey. Switching costs were estimated for a practice of 1,000 patients with relevant conditions by therapeutic area and for an insurance plan with 1 million individuals by therapeutic area and all areas combined. Switching cost drivers were assessed with one-way sensitivity analyses. RESULTS: Physicians expected extra 6 minutes for the NMS visit and 22 minutes over 3 months; NMS rates of 14.4%, 15.5%, and 17.7%; and 11.3%, 16.2%, and 33.2% of time not reimbursed for gastroenterology, rheumatology, and dermatology, respectively. The total switching costs for payer's were $771,460 (for n = 3,609 patients with an NMS rate of 16.6%), mostly due to follow-up visits and additional laboratory tests/procedures. In sensitivity analyses, the NMS rate was the main cost driver. Increasing the NMS rate to 25% and 50% increased payer's total switching costs to $1.19 and $2.39 million, respectively. CONCLUSIONS: Originator-to-biosimilar NMS in stable patients with autoimmune conditions could result in considerable switching costs for both providers and payers.

Healthcare Providers Underestimate Patients' Glucocorticoid Use in Crohn's Disease.

BACKGROUND: One of the therapy goals for Crohn's disease (CD) is glucocorticoid-free remission. Studies have shown care setting-specific variations in inflammatory bowel disease (IBD) management. AIMS: The principal objective of this study was to assess concordance between patient-reported and physician-reported outcomes in two different care settings (IBD centers and community practices). METHODS: Data of overall and long-term (≥ 3 months) glucocorticoid, immunosuppressant, and biologics use in participants ≥ 18 years old with a confirmed diagnosis of CD were collected. HCPs were grouped by IBD centers and community practices. Quality of life (using EuroQol 5D [EQ-5D]) and work/activity days lost were assessed. Agreement between patients' and HCPs' responses to survey questions was tested using kappa statistics. RESULTS: Data from 812 patients were examined. Significantly more patients versus HCPs reported oral glucocorticoid use (25.9% vs. 20.8%, κ = 0.735, P < 0.0001). Long-term use of oral glucocorticoids was similar for patients versus HCPs (67.7% vs. 63.8%, κ = 0.598, P = 0.53). Immunosuppressant use was 52.4% vs. 51.1% (κ = 0.784) and biologics use was 49.5% vs. 47.0% (κ = 0.909) for patients vs. HCPs. Patients and HCPs reported greater rates of symptom improvement with vs without biologic therapy (patients: 33.3% vs 16.8%; HCPs: 29.3% vs 13.5%, both P < 0.001). Patients with versus without routine follow-up were less likely to be treated with long-term glucocorticoid monotherapy (10.3% vs. 20.7%, P < 0.01) and had fewer lost work/activity days (5 vs. 8 days, P < 0.05). CONCLUSIONS: Patients reported more oral glucocorticoid use than physicians thought. Routine follow-up and higher rates of biologic use are associated with improvement in disease symptoms and general health among patients with CD.

Reduced Imaging Radiation Exposure and Costs Associated with Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.

BACKGROUND: Radiation exposure from diagnostic imaging may increase cancer risk of Crohn's disease (CD) patients, who are already at increased risk of certain cancers. AIM: To compare imaging radiation exposure and associated costs in CD patients during the year pre- and post-initiation of anti-tumor necrosis factor (anti-TNF) agents or corticosteroids. METHODS: Adults were identified from a large US claims database between 1/1/2005 and 12/31/2009 with ≥ 1 abdominal imaging scan and 12 months of enrollment before and after initiating therapy with anti-TNF or corticosteroids. Imaging utilization, radiation exposure, and healthcare costs pre- and post-initiation were examined. RESULTS: Anti-TNF-treated patients had significantly fewer imaging examinations the year prior to initiation than corticosteroid-treated patients. Cumulative radiation doses before initiation were significantly higher for corticosteroid patients compared to anti-TNF patients (22.3 vs. 17.7 millisieverts, P = 0.0083). After therapy initiation, anti-TNF-treated patients had significantly fewer imaging examinations (2.9 vs. 5.2, P < 0.0001) and less radiation exposure (7.4 vs. 15.4 millisieverts, P <0.0001) than corticosteroid-treated patients in the follow-up period. Reductions in imaging costs adjusted for 1000 patient-years after initiation of therapy were - $275,090 and - $121,960 (P = 0.0359) for anti-TNF versus corticosteroid patients, respectively. CONCLUSIONS: This analysis demonstrated that patients treated with anti-TNF agents have fewer imaging examinations, less radiation exposure, and lower healthcare costs associated with imaging than patients treated with corticosteroids. These benefits do not account for additional long-term benefits that may be gained from reduced radiation exposure.

Risk of Ocular Complications in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis.

PURPOSE: Noninfectious uveitis results in vision loss and ocular complications without adequate treatment. We compared the risk of developing ocular complications between patients with noninfectious intermediate uveitis, posterior uveitis, or panuveitis (NIIPPU) and matched controls. DESIGN: Retrospective analysis of insurance claims data (OptumHealth, Eden Prairie, MN; January 1, 1998-March 31, 2012). PARTICIPANTS: Cases 18 to 64 years of age with 2 or more NIIPPU diagnoses (International Classification of Diseases, 9th Revision, Clinical Modification codes) were matched 1:1 by sex, age, region, company, employment status, and index date with controls without uveitis. Patients with an ocular complication during baseline were excluded. METHODS: Continuous eligibility for 6 months or more before the first NIIPPU diagnosis date was required. Risks of ocular complications developing during patients' continuous eligibility in the study period were compared using unadjusted Kaplan-Meier survival analysis to estimate risk of and time to complications and adjusted Cox regression analysis to estimate hazard ratios (HRs). MAIN OUTCOME MEASURES: Percentages of cases and controls who demonstrate ocular complications and 1-, 5-, and 10-year risks and HRs for each complication. RESULTS: Mean age of the 1769 cases and matched controls was 47 years and 47% were men; 302 cases had persistent NIIPPU. During the study period, NIIPPU cases had a higher risk of any ocular complication (P < 0.001); the 5-year risk of any ocular complication was 66% for patients versus 24% for controls. Specifically, NIIPPU patients had greater 5-year risks of glaucoma (20% vs. 9%), cataract (35% vs. 13%), visual disturbance (29% vs. 9%), blindness or low vision (5% vs. 0.5%), retinal detachment (11% vs. 0.8%), and retinal disorder (28% vs. 2%) compared with controls. Hazard ratios indicated greater risks of ocular complications in cases versus controls during the overall observation period (HR, 5.2 for any ocular complication; HR, 4.8 for visual disturbance; HR, 3.2 for cataract; and HR, 2.7 for glaucoma; all P < 0.001). Hazard ratios for persistent cases indicated even greater risks. CONCLUSIONS: Noninfectious intermediate uveitis, posterior uveitis, or panuveitis, particularly persistent disease, is associated with a substantial risk of ocular complications. Optimal treatment initiatives remain imperative to reduce the ocular complication-related burden of NIIPPU.

Increased risk of venous thromboembolic events with corticosteroid vs biologic therapy for inflammatory bowel disease.

BACKGROUND & AIMS: We investigated whether treatment of active inflammatory bowel disease with biologic agents is associated with a reduced risk of venous thromboembolic events (VTEs) compared with corticosteroid therapy. METHODS: We performed a retrospective analysis of 15,100 adults with inflammatory bowel disease who were identified from the Truven Health MarketScan databases. We analyzed data from patients who received 6 months of continuous medical and prescription coverage before and 12 months after their first diagnosis and had no VTE during the 6 months before they first received biologic or corticosteroid therapy. The outcome assessed was any VTE that occurred during the 12-month follow-up period. A multivariate logistic regression model was used to evaluate the effects of biologic, corticosteroid, and combination therapies (biologics and corticosteroids) on VTE risk. RESULTS: Three hundred twenty-five VTEs occurred during the study period (in 2.25% of patients receiving only corticosteroids, in 0.44% of patients receiving biologics, and in 2.49% of patients receiving combination therapy). Compared with patients receiving only corticosteroids, the odds ratio for VTE in patients receiving only biologics was 0.21 (95% confidence interval, 0.05-0.87) in the multivariate model, and the odds ratio for VTE in patients on combination therapy was 1.01. CONCLUSIONS: Compared with treatment with only a biologic agent, corticosteroid therapy is associated with a nearly 5-fold increase in risk for VTE. Combination therapy with corticosteroids and biologic agents was associated with the same risk for VTE as that of corticosteroids alone. Corticosteroids therefore appear to increase risk for VTE.

Adalimumab therapy is associated with reduced risk of hospitalization in patients with ulcerative colitis.

BACKGROUND & AIMS: Adalimumab is effective for induction and maintenance of remission in patients with moderate to severe ulcerative colitis (UC). We assessed whether adalimumab, in addition to standard UC therapy, reduced the risk for hospitalization (from all causes, from complications of UC, or from complications of UC or the drugs used to treat it) and colectomy in patients with moderate to severe UC compared with placebo. METHODS: Data were combined from patients that received induction therapy (a 160-mg dose followed by an 80-mg dose of adalimumab) or placebo in 2 trials (ULTRA 1 and ULTRA 2; n = 963). The risks of hospitalization and colectomy were compared between groups using unadjusted rates during the 8-week induction period, and patient-year-adjusted rates during 52 weeks. Statistical differences between groups were determined using the χ(2) method and Z score normal approximations. Numbers of hospitalizations were compared using Poisson regression with time offset. RESULTS: Significant reductions in risk of all-cause, UC-related, and UC- or drug-related hospitalizations (by 40%, 50%, and 47%, respectively; P < .05 for all comparisons) were observed within the first 8 weeks of adalimumab therapy compared with placebo. Significantly lower incidence rates for all-cause (0.18 vs 0.26; P = .03), UC-related (0.12 vs 0.22; P = .002), and UC- or drug-related (0.14 vs 0.24; P = .005) hospitalizations were observed during 52 weeks of adalimumab therapy compared with placebo. Rates of colectomy did not differ significantly between patients given adalimumab vs placebo. CONCLUSIONS: In patients with moderate to severe UC, the addition of adalimumab to standard of care treatment reduced the number of hospitalizations for any cause, as well as for UC-related and UC- or drug-related complications, compared with placebo. ClinicalTrials.gov numbers, NCT00385736 and NCT00408629.

Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: Data from ULTRA 1, 2, and 3.

OBJECTIVES: The safety and efficacy of adalimumab for patients with moderately to severely active ulcerative colitis (UC) has been reported up to week 52 from the placebo-controlled trials ULTRA (Ulcerative Colitis Long-Term Remission and Maintenance with Adalimumab) 1 and 2. Up to 4 years of data for adalimumab-treated patients from ULTRA 1, 2, and the open-label extension ULTRA 3 are presented. METHODS: Remission per partial Mayo score, remission per Inflammatory Bowel Disease Questionnaire (IBDQ) score, and mucosal healing rates were assessed in adalimumab-randomized patients from ULTRA 1 and 2 up to week 208. Corticosteroid-free remission was assessed in adalimumab-randomized patients who used corticosteroids at lead-in study baseline. Maintenance of remission per partial Mayo score and mucosal healing was assessed in patients who entered ULTRA 3 in remission per full Mayo score and with mucosal healing, respectively. As observed, last observation carried forward (LOCF) and nonresponder imputation (NRI) were used to report efficacy. Adverse events were reported for any adalimumab-treated patient. RESULTS: A total of 600/1,094 patients enrolled in ULTRA 1 or 2 were randomized to receive adalimumab and included in the intent-to-treat analyses of the studies. Of these, 199 patients remained on adalimumab after 4 years of follow-up. Rates of remission per partial Mayo score, remission per IBDQ score, mucosal healing, and corticosteroid discontinuation at week 208 were 24.7%, 26.3%, 27.7% (NRI), and 59.2% (observed), respectively. Of the patients who were followed up in ULTRA 3 (588/1,094), a total of 360 patients remained on adalimumab 3 years later. Remission per partial Mayo score and mucosal healing after ULTRA 1 or 2 to year 3 of ULTRA 3 were maintained by 63.6% and 59.9% of patients, respectively (NRI). Adverse event rates were stable over time. CONCLUSIONS: Remission, mucosal healing, and improved quality of life were maintained in patients with moderately to severely active UC with long-term adalimumab therapy, for up to 4 years. No new safety signals were reported.

Multiscale adaptive marginal analysis of longitudinal neuroimaging data with time-varying covariates.

Neuroimaging data collected at repeated occasions are gaining increasing attention in the neuroimaging community due to their potential in answering questions regarding brain development, aging, and neurodegeneration. These datasets are large and complicated, characterized by the intricate spatial dependence structure of each response image, multiple response images per subject, and covariates that may vary with time. We propose a multiscale adaptive generalized method of moments (MA-GMM) approach to estimate marginal regression models for imaging datasets that contain time-varying, spatially related responses and some time-varying covariates. Our method categorizes covariates into types to determine the valid moment conditions to combine during estimation. Further, instead of assuming independence of voxels (the components that make up each subject's response image at each time point) as many current neuroimaging analysis techniques do, this method "adaptively smoothes" neuroimaging response data, computing parameter estimates by iteratively building spheres around each voxel and combining observations within the spheres with weights. MA-GMM's development adds to the few available modeling approaches intended for longitudinal imaging data analysis. Simulation studies and an analysis of a real longitudinal imaging dataset from the Alzheimer's Disease Neuroimaging Initiative are used to assess the performance of MA-GMM. Martha Skup, Hongtu Zhu, and Heping Zhang for the Alzheimer's Disease Neuroimaging Initiative.

Discontinuation and Switchback After Non-Medical Switching from Originator Tumor Necrosis Factor Alpha (TNF) Inhibitors to Biosimilars: A Meta-Analysis of Real-World Studies from 2012 to 2018.

INTRODUCTION: To examine the prevalence rates of biosimilar discontinuation and switchback to the originator tumor necrosis factor alpha (TNF) inhibitors following non-medical switch (NMS) in patients. METHODS: Real-world studies reporting biosimilar discontinuation and switchback rates following NMS published between January 2012 and August 2018 were identified through a systematic literature review. A meta-analysis estimated the annualized discontinuation and switchback rates. A subsequent meta-analysis assessed annualized incremental discontinuation rate among studies reporting both discontinuation rates in patients who underwent an NMS (switchers) and patients who remained on originators (non-switchers). RESULTS: A total of 66 publications were identified: 31 in gastroenterology, 32 in rheumatology, and 3 in both. Half of the studies reported switchback rates; only 9 studies reported discontinuation rates for both switchers and non-switchers. Across studies, the mean/range sample size of the NMS patient population was 136/9-1641; mean/range follow-up was 10/3-24 months. Annualized biosimilar discontinuation rate was 21% (95% confidence interval [CI] 18%, 25%). Switchback rate was 14% (95% CI 10%, 17%) among all NMS patients and 62% (95% CI 44%, 80%) among discontinuers. The mean/range sample size of switchers and non-switchers was 344/89-1621 and 768/19-2870, respectively; mean/range follow-up was 11/6-18 and 12/6-8 months, respectively. Annualized incremental biosimilar discontinuation rate was 18% (95% CI 4%, 31%). CONCLUSION: Biosimilar discontinuation was found to be prevalent among patients who underwent an NMS from an originator TNF inhibitor to its biosimilar(s) in the real world. In addition, switchback to the originator TNF inhibitors was common following biosimilar discontinuation. Careful consideration is necessary when switching patients already on an originator TNF inhibitor to its biosimilar(s). Main limitations included the heterogeneity of the studies and the limited comparability of the data.

Inhibitory motor control in response stopping and response switching.

While much is known about the neural regions recruited in the human brain when a dominant motor response becomes inappropriate and must be stopped, less is known about the regions that support switching to a new, appropriate, response. Using functional magnetic resonance imaging with two variants of the stop-signal paradigm that require either stopping altogether or switching to a different response, we examined the brain systems involved in these two forms of executive control. Both stopping trials and switching trials showed common recruitment of the right inferior frontal gyrus, presupplementary motor area, and midbrain. Contrasting switching trials with stopping trials showed activation similar to that observed on response trials (where the initial response remains appropriate and no control is invoked), whereas there were no regions that showed significantly greater activity for stopping trials compared with switching trials. These results show that response switching can be supported by the same neural systems as response inhibition, and suggest that the same mechanism of rapid, nonselective response inhibition that is thought to support speeded response stopping can also support speeded response switching when paired with execution of the new, appropriate, response.

Sex differences in grey matter atrophy patterns among AD and aMCI patients: results from ADNI.

We used longitudinal magnetic resonance imaging (MRI) data to determine whether there are any gender differences in grey matter atrophy patterns over time in 197 individuals with probable Alzheimer's disease (AD) and 266 with amnestic mild cognitive impairment (aMCI), compared with 224 healthy controls participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). While previous research has differentiated probable AD and aMCI groups from controls in brain atrophy, it is unclear whether and how sex plays a role in patterns of change over time. Using regional volumetric maps, we fit longitudinal models to the grey matter data collected at repeated occasions, seeking differences in patterns of volume change over time by sex and diagnostic group in a voxel-wise analysis. Additionally, using a region-of-interest approach, we fit longitudinal models to the global volumetric data of predetermined brain regions to determine whether this more conventional approach is sufficient for determining sex and group differences in atrophy. Our longitudinal analyses revealed that, of the various grey matter regions investigated, males and females in the AD group and the aMCI group showed different patterns of decline over time compared to controls in the bilateral precuneus, bilateral caudate nucleus, right entorhinal gyrus, bilateral thalamus, bilateral middle temporal gyrus, left insula, and right amygdala. As one of the first investigation to model more than two time points of structural MRI data over time, our findings add insight into how AD and aMCI males and females differ from controls and from each other over time.

A developmental neuroimaging investigation of the change paradigm.

This neuroimaging study examines the development of cognitive flexibility using the Change task in a sample of youths and adults. The Change task requires subjects to inhibit a prepotent response and substitute an alternative response, and the task incorporates an algorithm that adjusts task difficulty in response to subject performance. Data from both groups combined show a network of prefrontal and parietal areas that are active during the task. For adults vs. youths, a distributed network was more active for successful change trials versus go, baseline, or unsuccessful change trials. This network included areas involved in rule representation, retrieval (lateral PFC), and switching (medial PFC and parietal regions). These results are consistent with data from previous task-switching experiments and inform developmental understandings of cognitive flexibility.

Altered neural function in pediatric bipolar disorder during reversal learning.

OBJECTIVE: Data documenting the functional impairment associated with the diagnosis of bipolar disorder (BD) in children and adolescents highlight the need for greater understanding of its pathophysiology. Toward that end, we demonstrated previously that BD youth have behavioral deficits on reversal learning tasks. On such tasks, participants must first acquire a stimulus/response relationship through trial-and-error learning, and then discern when the stimulus/reward relationship reverses. Here, we use event-related functional magnetic resonance imaging (fMRI) to elucidate neural correlates of reversal learning deficits in euthymic BD youth compared to typically developing controls. METHOD: We compared euthymic pediatric BD participants (n = 16) versus age-, sex-, and IQ-matched controls (n = 16). Our main outcome measure was blood oxygen level-dependent (BOLD) signal measured with fMRI during an event-related probabilistic reversal task. RESULTS: Pediatric BD participants had significantly greater neural activity than controls in fronto-parietal regions during the reversal phase, particularly in response to punished reversal errors (p < 0.05 corrected for multiple comparisons). CONCLUSIONS: Our current study suggests that during reversal learning, BD youths inefficiently recruit regions associated with processing response conflict and implementing alternative responses, including subdivisions of the frontal cortex and the parietal cortex. Such deficits are present in euthymic BD youth. Further work is necessary to evaluate the specificity of such alterations.

Comparison of Biologics and Oral Treatments for Plaque Psoriasis: A Meta-analysis.

Importance: The clinical benefits of novel treatments for moderate to severe psoriasis are well established, but wide variations exist in patient response across different therapies. In the absence of head-to-head randomized trials, meta-analyses synthesizing data from multiple studies are needed to assess comparative efficacy among psoriasis treatments. Objective: To estimate the relative short-term and long-term efficacy of biologics and oral agents for the treatment of moderate to severe psoriasis. Data Sources: A systematic literature review was conducted on December 4, 2017, and updated on September 17, 2018. The Embase, MEDLINE, and Cochrane Central Register databases were included. Study Selection: Phase 2, 3, or 4 randomized clinical trials of treatments licensed by the US Food and Drug Administration and the European Medicines Agency for adults with moderate to severe psoriasis with data on Psoriasis Area and Severity Index assessment of 75%, 90%, and 100% reductions (PASI 75, 90, and 100) at 10 to 16 weeks (short-term efficacy) or 44 to 60 weeks (long-term efficacy) from baseline. Data Extraction and Synthesis: Data were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. A bayesian network meta-analysis was conducted to estimate short-term PASI response rates; to account for variation across trials, an ordinal model that adjusted for reference arm response was implemented. The long-term PASI rates were estimated via a traditional meta-analysis. Main Outcomes and Measures: PASI 75, 90, and 100 response rates at 10 to 16 weeks and 44 to 60 weeks from baseline. Results: Sixty trials meeting all inclusion criteria were included. At weeks 10 to 16, the highest PASI 90 rates were seen with risankizumab-rzaa (71.6%; 95% credible interval [CrI], 67.5%-75.4%), brodalumab (70.8%; 95% CrI, 66.8%-74.6%), ixekizumab (70.6%; 95% CrI, 66.8%-74.6%), and guselkumab (67.3%; 62.5%-71.9%). At weeks 44 to 60, the treatments with the highest PASI 90 rates were risankizumab-rzaa (79.4%, 95% CI, 75.5%-82.9%), guselkumab (76.5%; 95% CI, 72.1%-80.5%), brodalumab (74.0%; 95% CI, 69.3%-78.1%), and ixekizumab (73.9%; 95% CI, 69.9%-77.5%). Findings were consistent for short-term and long-term PASI 75 and 100 responses. Conclusions and Relevance: This study provides an assessment of the comparative efficacy among treatments for moderate to severe plaque psoriasis. The meta-analysis suggests that brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa were associated with the highest PASI response rates in both short-term and long-term therapy.

Economic Impact of Non-Medical Switching from Originator Biologics to Biosimilars: A Systematic Literature Review.

INTRODUCTION: A systematic literature review was conducted to review and summarize the economic impact of non-medical switching (NMS) from biologic originators to their biosimilars (i.e., switching a patient's medication for reasons irrelevant to the patient's health). METHODS: English publications reporting healthcare resource utilization (HRU) or costs associated with biosimilar NMS were searched in PubMed and EMBASE over the past 10 years and from selected scientific conferences over the past 3 years, along with gray literature for all biologics with an approved biosimilar (e.g., tumor-necrosis factor inhibitors, erythropoiesis-stimulating agents, insulin and hormone therapies). RESULTS: A total of 1311 publications were retrieved, where 54 studies met the selection criteria. Seventeen studies reported increased real-world HRU or costs related to biosimilar NMS, e.g., higher rates of surgery (11%), steroid use (13%) and biosimilar dose escalating (6-35.4%). Among the studies that the estimated cost impact associated with NMS, 33 reported drug costs reduction, 12 reported healthcare costs post-NMS without a detailed breakdown, and 5 reported NMS setup and managing costs. Cost estimation/simulation studies demonstrated the cost reduction associated with NMS. However, variation across studies was substantial because of heterogeneity in study designs and assumptions (e.g., disease areas, scenarios of drug price discount rates, cost components, population size, study period, etc.). CONCLUSION: Real-world studies reporting the economic impact of biosimilar NMS separately from drug costs are emerging, and those that reported such results found increased HRU in patients with biosimilar NMS. Studies of cost estimation have been largely limited to drug prices. Comprehensive evaluation of the economic impact of NMS should incorporate all important elements of healthcare service needs such as drug price, biologic rebates, HRU, NMS program setup, administration and monitoring costs. FUNDING: AbbVie.

Risk of Developing Additional Immune-Mediated Manifestations: A Retrospective Matched Cohort Study.

INTRODUCTION: Immune-mediated inflammatory diseases (IMIDs) cause significant impairment in quality of life. Although they share similar genetic factors, environmental precipitants, and pathophysiological mechanisms, there is little evidence on the risk of developing subsequent IMIDs after an initial IMID diagnosis. We sought to assess the risk of developing subsequent IMIDs among patients diagnosed with an initial IMID. METHODS: This retrospective matched cohort study used a large US commercial health insurance claims database (01/01/2006-09/30/2015). The risks of developing secondary IMIDs among patients aged 18-64 years with a diagnosis of one of nine IMIDs of interest (ankylosing spondylitis, celiac disease, hidradenitis suppurativa [HS], inflammatory bowel disease, lupus, psoriatic arthritis [PsA], psoriasis, rheumatoid arthritis, and uveitis) as identified from diagnosis codes on medical claims were compared with up to 1000 matched controls without the primary IMID using Cox proportional hazards models. RESULTS: Across the nine IMIDs of interest, there were 398,935 unique case patients matched to 256,795,796 non-unique control patients. Case patients with an initial IMID had higher risks of developing each, any one, and any two of the other eight secondary IMIDs compared to their matched controls. Hazard ratios [95% confidence intervals] for the risk of developing any one secondary IMID ranged from 5.4 [5.0, 5.8] (initial IMID: HS) to 62.2 [59.9, 64.6] (initial IMID: PsA), and hazard ratios for developing any two secondary IMIDs ranged from 3.0 [2.3, 3.8] (HS) to 75.2 [69.3, 81.7] (PsA). CONCLUSIONS: This study demonstrates that the risk of developing a second IMID is significantly higher for individuals who have already experienced a first IMID in a large and contemporary US claims database. Certain pairs of IMIDs co-occur more frequently than others. The risk of developing subsequent IMIDs may be an important consideration for clinicians when selecting treatment strategies. FUNDING: Abbvie.

Processing of differentially valued rewards and punishments in youths with bipolar disorder or severe mood dysregulation.

BACKGROUND: Youths with chronic irritability and hyperarousal (i.e., severe mood dysregulation, SMD) have reward- and punishment-processing deficits distinct from those exhibited by children with episodic symptoms of mania (i.e., narrow-phenotype bipolar disorder, BD). Additionally, youths with SMD, like those with psychopathy, have prominent reactive aggression. Therefore, we hypothesized that SMD, but not BD, youths would be impaired on a decision-making task that has identified reward- and punishment-processing deficits in individuals with psychopathy. METHODS: A decision-making task was used in which BD (n = 23), SMD (n = 37), and control subjects (n = 31) were asked to choose between two images associated with different levels of reward or punishment. RESULTS: No between-group differences in task performance were found. CONCLUSION: These results suggest that BD, SMD, and normal youths do not differ in their ability to select between rewards and punishments of different value. Effect-size analyses suggest that this finding is not secondary to a type II error. Unlike individuals with psychopathy, neither SMD subjects nor those with BD differ from controls in their ability to select between differentially valued rewards and punishments.

Systematic review and network meta-analysis: effect of biologics on radiographic progression in rheumatoid arthritis.

AIM: To evaluate the comparative effectiveness of biologics in inhibiting radiographic progression among rheumatoid arthritis (RA) patients. MATERIALS & METHODS: Bayesian network meta-analysis of published trials investigating the USA FDA approved biologics treatment in RA patients, using methotrexate (MTX) as the reference comparator. RESULTS: Nine trials met the inclusion criteria for base case analysis. Compared with MTX, most biologics (except golimumab) + MTX had significantly lower rates of radiographic progression at 1 year. Mean difference in radiographic progression rates between MTX monotherapy and biologics + MTX was highest for adalimumab + MTX (-3.8) and lowest for tocilizumab + MTX (-0.7). Inhibition of radiographic progression was sustained. CONCLUSION: Biologics inhibit radiographic progression in patients with RA at 1 year; however, published evidence beyond 1 year is limited.

Is Patient Support Program Participation Associated with Longer Persistence and Improved Adherence Among New Users of Adalimumab? A Retrospective Cohort Study.

INTRODUCTION: Adalimumab (ADA) is a medication used in the treatment of several autoimmune diseases. Despite the beneficial effects of ADA, its adherence and persistence rates are low. Patients treated with ADA from Clalit Health Services (CHS) can enroll in AbbVie's patient support program (PSP), which aims to improve ADA adherence and persistence. Therefore, we examine whether PSP participation is associated with a longer persistence and/or an improved adherence to ADA. METHODS: A real-world retrospective cohort study of all new ADA users from CHS, comparing those enrolled in the offered PSP to those not enrolled. The data regarding PSP users can be tracked using CHS's data warehouse. The index date was defined as the date of the patients' first purchase of ADA occurring between August 1, 2012 and December 31, 2014. The follow-up data were collected at 12, 24, and 36 months. Persistence was assessed using survival analyses of time until discontinuation, and adherence was assessed using medication possession ratio (MPR). RESULTS: There were 1520 patients in the study, 755 (49.7%) of whom were PSP users. PSP users were 54.3% female vs. 51.9% among non-PSP users (p = 0.355) and they were significantly younger than non-PSP users (mean age 42.3 vs. 45.0 years, p = 0.002) The PSP and non-PSP users' persistence was 673 and 574 days, respectively (p < 0.001). Further, the PSP users were more likely than the non-PSP users to be persistently taking medication at the 12-month follow-up (57.5% vs. 45.6%, p < 0.001). The 12-month mean adherence rate among those with at least 12 months of persistence was significantly improved for the PSP users compared to the non-PSP users (94.1% vs. 92.9%, p = 0.026). CONCLUSION: The AbbVie PSP provided to CHS patients was associated with a longer persistence among new users of ADA. It was also associated with significantly higher adherence rate within the first 12 months. FUNDING: AbbVie Inc.

Development of the Rheumatoid Arthritis Symptom Questionnaire (RASQ): a patient reported outcome scale for measuring symptoms of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA), a chronic, progressive inflammatory, autoimmune disease, can substantially reduce health-related quality of life (HRQoL) and lead to severe disability and early mortality. Patient-reported outcome (PRO) instruments are used to assess the patient experience of RA symptoms and impacts, and can capture RA treatment effects. To address limitations in existing PRO instruments, this research aimed to establish the content validity of a new instrument, the Rheumatoid Arthritis Symptom Questionnaire (RASQ), to assess the signs and symptoms of RA. METHOD: The most important and relevant sign and symptom concepts for RA patients were identified through a targeted review of the published literature, expert opinion, and concept elicitation patient interviews. Cognitive interviews were conducted with patients to test the comprehensibility and comprehensiveness of the RASQ. RESULTS: Seven symptoms emerged consistently across the conceptual research: joint pain, joint swelling, joint stiffness, joint tenderness, joint warmth, muscle pain, and tiredness. Draft item content was developed to assess these symptoms, in addition to a single impact item, resulting in three RASQ versions: two utilizing a 7 day recall period (one assessing symptoms at their worst, the other on average) and a third using a 24 hour recall period assessing symptoms at their worst. Cognitive interview results demonstrated patient understanding and ability to use the instrument. CONCLUSIONS: Content validity of the RASQ was established in accordance with instrument development guidelines. The RASQ fills a measurement gap by assessing the RA signs and symptoms most important to patients. Research evaluating the RASQ's psychometric properties is underway.