Hybrid Closure of Postinfarction Apical Ventricular Septal Defect Using Septal Occluder Device and Right Ventricular Free Wall: The Apical BASSINET Concept.

BACKGROUND: Postinfarction ventricular septal defect (VSD) is a catastrophic complication of myocardial infarction. Surgical repair still has poor outcomes. This report describes clinical outcomes after a novel hybrid transcatheter/surgical repair in patients with apical VSD. METHODS: Seven patients with postmyocardial infarction apical VSD underwent hybrid transcatheter repair via subxiphoid surgical access. A transcatheter occluder (Amplatzer Septal Occluder) with a trailing premounted suture was deployed through the right ventricular wall and through the ventricular septum into the left ventricular apex. The trailing suture was used to connect an anchor external to the right ventricular wall. Tension on the suture then collapses the right ventricular free wall against the septum and left ventricular occluder, thereby obliterating the VSD. Outcomes were compared with 9 patients who underwent surgical repair using either patch or primary suture closure. RESULTS: All patients had significant left-to-right shunt (Qp:Qs 2.5:1; interquartile range [IQR, 2.1-2.6] hybrid repair versus 2.0:1 [IQR, 2.0-2.5] surgical repair), and elevated right ventricular systolic pressure (62 [IQR, 46-71] versus 49 [IQR, 43-54] mm Hg, respectively). All had severely depressed stroke volume index (22 versus 21 mL/m2) with ≈45% in each group requiring mechanical support preprocedurally. The procedure was done 15 (IQR, 10-50) versus 24 (IQR, 10-134) days postmyocardial infarction, respectively. Both groups of patients underwent repair with technical success and without intraprocedural death. One patient in the hybrid group and 4 in the surgical group developed multiorgan failure. The hybrid group had a higher survival at discharge (86% versus 56%) and at 30 days (71% versus 56%), but similar at 1 year (57% versus 56%). During follow-up, 1 patient in each group required reintervention for residual VSD (hybrid: 9 months versus surgical: 5 days). CONCLUSIONS: Early intervention with a hybrid transcatheter/surgical repair may be a viable alternative to traditional surgery for postinfarction apical VSD.

Real-world outcomes and direct care cost before and after elexacaftor/tezacaftor/ivacaftor initiation in commercially insured members with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a chronic, progressive genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene resulting in a dysfunctional CFTR protein. Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is a triple combination oral drug therapy with an annual cost greater than $300,000 and available to nearly 90% of the CF population based on age and genotype. Limited real-world direct medical cost offset data are available for ELX/TEZ/IVA among commercially insured individuals. OBJECTIVE: To describe and compare total cost of care and health care resource utilization (HRU) 180 days before and 180 days after first ELX/TEZ/IVA drug claim among CFTR modulator treatment-naive, commercially insured members. METHODS: This study was a retrospective analysis of integrated pharmacy and medical claims data from 17.9 million commercially insured members. A 180-day prestudy and 180-day poststudy design was used to compare outcomes prior to and following ELX/TEZ/IVA initiation. Study inclusion was limited to members with first ELX/TEZ/IVA claim (index date) between October 21, 2019, and December 31, 2021, continuously enrolled 180 days before and 180 days after index date, and no CFTR-modulator drug claim 180 days prior to index date. Total paid amounts from medical and pharmacy claims after network discounts (defined as total cost of care), HRU, and pulmonary exacerbation events were summarized using descriptive statistics and compared using Wilcoxon signed rank test. RESULTS: 494 members newly initiating ELX/TEZ/IVA met inclusion criteria. Prestudy to poststudy mean member total cost of care increased from $58,180 to $198,815 (difference: $140,635; P < 0.001). Mean member medical benefit costs decreased from $28,764 to $12,484 (difference: -$16,280; P < 0.001), whereas mean member pharmacy benefit costs increased from $29,416 to $186,331 (difference: $156,915; P < 0.001). Mean member inpatient hospitalizations (62% absolute reduction; P < 0.001), emergency department visits (43% absolute reduction; P < 0.01), and pulmonary exacerbation events (44% absolute reduction; P < 0.001) were significantly lower in the postperiod compared with the preperiod. CONCLUSIONS: Among members with CF newly initiating CFTR modulator with ELX/TEZ/IVA, mean member total cost of care increased 3-fold despite significant and meaningful reductions in pulmonary exacerbation events, HRU, and medical benefit spend. Pharmacy benefit spend outpaced medical benefit spend at a rate of $9.64 to $1 in the 180 days following ELX/TEZ/IVA initiation. Real-world data should be used to objectively measure the clinical and economic benefits of costly medications, such as CFTR modulators, to align price with value. DISCLOSURES: Drs Marshall, Espinosa, Starner, and Gleason are employees of Prime Therapeutics. The study was funded by Prime Therapeutics.

Transcatheter Mitral Valve Replacement in Failed Bioprosthetic Valve, Ring, and Mitral Annular Calcification Associated Mitral Valve Disease Using Balloon Expandable Transcatheter Heart Valve.

Transcatheter mitral valve replacement (TMVR) using the SAPIEN platform has been performed in failed bioprosthetic valves (valve-in-valve), surgical annuloplasty rings (valve-in-ring), and native valves with mitral annular calcification (MAC) (valve-in-MAC). Experience over the past decade has identified important challenges and solutions to improve clinical outcomes. In this review, we discuss the indication, trend in utilization, unique challenges, procedural planning, and clinical outcomes of valve-in-valve, valve-in-ring, and valve-in-MAC TMVR.

A Comparison of Thirty-Day Clinical and Echocardiographic Outcomes of Patients Undergoing Transcatheter vs. Surgical Aortic Valve Replacement for Native Aortic Insufficiency.

OBJECTIVES: We aim to compare in-hospital and 30-day outcomes of transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) for native aortic insufficiency (AI). BACKGROUND: TAVR is increasingly used off-label in patients with AI deemed high risk for SAVR. There is a paucity of data comparing TAVR and SAVR with current commercially available TAVR devices. METHODS: A single-center, retrospective cohort study of patients undergoing TAVR or SAVR for native AI between 2014 and 2020 was performed. Data were obtained from the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database, Transcatheter Valve Therapy (TVT) registry, and chart review. In-hospital and 30-day outcomes are reported. RESULTS: Of 125 total patients, 91 underwent SAVR and 34 underwent TAVR. The TAVR group had a higher STS predictive risk of mortality (PROM) (TAVR = 3.96 %, SAVR = 1.25 %, p < 0.0001). In the postoperative period, the SAVR group had higher rates of new-onset atrial fibrillation (20.9 % vs. 0 %, p < 0.001), while the TAVR group had higher rates of complete heart block requiring permanent pacemaker implantation (20.6 % vs. 2.2 %, p < 0.001). There was no difference in in-hospital or 30-day mortality, stroke, myocardial infarction, residual AI, or repeat valve intervention. CONCLUSIONS: Despite higher STS PROM and more comorbidities, patients who underwent TAVR for AI had similar in-hospital and 30-day outcomes as patients who underwent SAVR for AI. These results support TAVR in selected high-risk patients with AI, with the knowledge that pacemaker needs may be higher than patients undergoing SAVR.

Drug super spender tsunami: An integrated medical and pharmacy benefits assessment.

BACKGROUND: As new rare-disease drug therapy, gene therapies, and high-priced cancer drugs receive US Food and Drug Administration approval, there is an increasing potential for drug super spender individuals with more than $250,000 annual drug cost. OBJECTIVE: To categorize all members in a large, commercially insured population by their total annual combined drug costs from both medical and pharmacy benefits and to determine the trend in drug super spender prevalence. METHODS: Using a commercially insured population with integrated medical and pharmacy benefits, all unique members with any enrollment between January 2016 and December 2019 were identified. The sum of total cost for all pharmacy claims plus all medical benefit claim lines for drugs was determined for each member, for each calendar year. Cost was defined as the plan plus member liability at network-discounted price, with no further adjustment for any coupons or rebates. Descriptive statistics were used to describe the drug super spender growth. RESULTS: There was an average of 17.9 million members per year with at least 1 month of eligibility through the 4-year study period. In 2016, a total of 2,994 members with more than $250,000 drug cost per member accounted for $1,324 million drug spend. In 2019, there were 5,894 super spender members (97% increase), accounting for $2,579 million drug cost (95% increase), which was 9.6% of $26,618 million total drug spend. CONCLUSIONS: In this large, commercially insured population, a small (32 per 100,000) number of drug super spender members comprise a disproportionate portion of the total drug expenditures, at $1 of every $10 dollars of total drug expenditures. Health plans need to understand the drug super spender trend and develop strategies to maintain health care affordability. DISCLOSURES: This study was funded internally by Prime Therapeutics LLC. Drs Starner and Gleason are employees of Prime Therapeutics LLC, a pharmacy benefits management company. Dr Bowen is a former employee of Prime Therapeutics LLC.

Evolving computed tomography angiography for aortic valve replacement: Optimizing transcatheter and surgical therapies.

Transcatheter aortic valve replacement (TAVR) has transformed the treatment of aortic stenosis and pre-procedure planning relies heavily on advanced imaging. Multidetector computed tomography angiography, the "TAVR CT," facilitates essential planning steps of measuring the aortic root for valve sizing and feasibility and assessment of potential access vessels, making it the guideline gold standard in preprocedural TAVR work up. This Impact of Advanced Imaging Techniques on Cardiac Surgery article will examine the development of TAVR CT, illustrate the current impact and utility, and highlight potential areas of future growth. Clinicians who keep informed of these changes and can become proficient with TAVR CT analyses will offer patients the most optimal results and fuel future therapeutic growth.

Aortic Dimensions Are Larger in Patients With Fibromuscular Dysplasia.

Background Fibromuscular dysplasia (FMD) is a disease of unknown etiology that causes stenosis, aneurysmal dilatation, and dissection of vascular beds. Known to affect medium-sized arteries, FMD is not typically considered to affect the aorta. We tested the hypothesis that aortic size in FMD is abnormal compared with age- and sex-matched controls. Methods and Results Medical records and computed tomography angiography images were reviewed in female patients with a diagnosis of FMD who were seen in the vascular medicine clinic at Emory Healthcare. Aortic dimensions were measured at 6 different landmarks. Using 2 sample t tests, the aortic measurements and height-indexed measurements were compared with published normal values in healthy women of a similar age. A total of 94 female patients were included in the study. The median age was 57 (interquartile range, 50-65). FMD involvement was present most commonly in the extracranial carotid (77.7%) and renal (43.6%) arteries. All 6 aortic segments were found to be larger in both absolute measures and height-indexed measures in the FMD population (P<0.001). The largest differences were observed within the absolute measures of the sinotubular junction with mean±SD (mm) (29.9±4.1) versus (27±2.5), ascending aorta (32.7±4.4) versus (30.0±3.5), and descending aorta (24.7±3.0) versus (22.0±2.0) (P<0.001). Conclusions Aortic diameters in female patients with FMD are larger when compared with published age- and sex-matched normal values. These findings suggest that FMD may also affect the large-sized arteries.

Use of transesophageal echocardiography for transcatheter valve-in-valve implantation for patients with prior bioprosthetic surgical aortic, mitral, tricuspid, and pulmonic valves.

Valve-in-valve (ViV) transcatheter procedures are the preferred option for redo valve replacement in patients who otherwise would be high risk for surgery. Transesophageal echocardiography (TEE) is an integral imaging modality for both peri-procedural and intra-procedural guidance during transcatheter ViV replacement. When intentional leaflet laceration is needed, such as with the BASILICA (Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstructions during TAVR) or LAMPOON (Laceration of the Anterior Mitral valve leaflet to Prevent left ventricular Outlet ObstructioN) procedures, TEE is critical to proper guidewire positioning and achieving a successful laceration. In this paper we detail the role of TEE in ViV transcatheter valve replacement in patients with prior surgical aortic, mitral, tricuspid, and pulmonic valves.

Single-Barrel, Double-Barrel, and Fenestrated Endografts to Facilitate Transcatheter Pulmonary Valve Replacement in Large RVOT.

OBJECTIVES: The aim of this study was to test the hypothesis that narrowing the landing zone using commercially available endografts would enable transcatheter pulmonary valve replacement (TPVR) using commercially available transcatheter heart valves. BACKGROUND: TPVR is challenging in an outsized native or patch-repaired right ventricular outflow tract (RVOT). Downsizing the RVOT for TPVR is currently possible only using investigational devices. In patients ineligible because of excessive RVOT size, TPVR landing zones were created using commercially available endografts. METHODS: Consecutive patients with native or patch-repaired RVOTs and high or prohibitive surgical risk were reviewed, and this report describes the authors' experience with endograft-facilitated TPVR (EF-TPVR) offered to patients ineligible for investigational or commercial devices. All EF-TPVR patients were surgery ineligible, with symptomatic, severe pulmonary insufficiency, enlarged RVOTs, and severe right ventricular (RV) enlargement (>150 ml/m2). TPVR and surgical pulmonary valve replacement (SPVR) were compared in patients with less severe RV enlargement. RESULTS: Fourteen patients had large RVOTs unsuitable for conventional TPVR; 6 patients (1 surgery ineligible) received investigational devices, and 8 otherwise ineligible patients underwent compassionate EF-TPVR (n = 5 with tetralogy of Fallot). Three strategies were applied on the basis of progressively larger RVOT size: single-barrel, in situ fenestrated, and double-barrel endografts as required to anchor 1 (single-barrel and fenestrated) or 2 (double-barrel) transcatheter heart valves. All were technically successful, without procedure-related, 30-day, or in-hospital deaths. Two late complications (stent obstruction and embolization) were treated percutaneously. One patient died of ventricular tachycardia 36 days after EF-TPVR. Compared with 48 SPVRs, RV enlargement was greater, but 30-day and 1-year mortality and readmission were no different. The mean transvalvular pressure gradient was lower after EF-TPVR (3.8 ± 0.8 mm Hg vs. 10.7 ± 4.1 mm Hg; p < 0.001; 30 days). More than mild pulmonary insufficiency was equivalent in both (EF-TPVR 0.0% [n = 0 of 8] vs. SPVR 4.3% [n = 1 of 43]; p = 1.00; 30 days). CONCLUSIONS: EF-TPVR may be an alternative for patients with pulmonic insufficiency and enlarged RVOTs ineligible for other therapies.

Antegrade Intentional Laceration of the Anterior Mitral Leaflet to Prevent Left Ventricular Outflow Tract Obstruction: A Simplified Technique From Bench to Bedside.

BACKGROUND: Intentional laceration of the anterior mitral leaflet (LAMPOON) is an effective adjunct to transcatheter mitral valve replacement that prevents left ventricular outflow tract (LVOT) obstruction. To date, LAMPOON has been performed in over 150 patients using a retrograde approach that can be technically challenging. A modified antegrade transseptal technique may simplify the procedure. METHODS: Antegrade LAMPOON was developed and tested in nonsurvival pig experiments. Thereafter, antegrade LAMPOON was performed in patients at prohibitive risk of LVOT obstruction. Clinical, procedural, and angiographic details were abstracted from medical records of their index procedure, and were compared with findings in comparable patients at risk of fixed-LVOT obstruction in the LAMPOON investigational device exemption trial. RESULTS: Eight patients at risk of fixed LVOT obstruction underwent antegrade LAMPOON. Leaflet traversal and laceration were technically successful in all. There were no cases of clinically significant LVOT obstruction (mean LVOT gradient at discharge: 5.4±1.4 mm Hg). One patient suffered a ventricular wire perforation, unrelated to the antegrade LAMPOON technique, and did not survive to discharge. At the time of discharge, no patients had an increase of >10 mm Hg in LVOT gradient compared with baseline. Procedure times (from traversal to transcatheter mitral valve replacement) were shorter, compared with the retrograde technique in the LAMPOON investigational device exemption trial (39±09 versus 65±35 minutes). All patients survived (8/8, 100%) the procedure, and 7/8 (88%) survived to 30 days, similar to subjects in the LAMPOON investigational device exemption trial. CONCLUSIONS: Antegrade LAMPOON is an effective, reproducible, and simplified strategy to lacerate the anterior leaflet before transcatheter mitral valve replacement. The authors recommend the technique as the new standard for LAMPOON.

Echocardiographic Predictors of Tricuspid Ring Annuloplasty Repair Failure for Functional Tricuspid Regurgitation.

OBJECTIVE: Significant tricuspid regurgitation (TR) recurs after tricuspid valve repair of functional TR in 15% to 20% within the first year, and 30% to 70% within 5 years. Prior investigations report leaflet tethering, and not tricuspid valve annular diameter (TVAD), as predictive of recurrent TR. The authors hypothesize that pre-repair TVAD is predictive of repair failure for functional TR. PARTICIPANTS: Fifty-four patients with functional TR scheduled for left heart surgery and tricuspid valve repair with ring annuloplasty. DESIGN: Retrospective study design. Pre- and post-repair transthoracic and intraoperative transesophageal echocardiographic data included left and right ventricular functions, tricuspid leaflet tethering height, TVAD, and TR severity. Successful repair was defined as ≤2+ TR. SETTING: Tertiary care medical center. INTERVENTIONS: None. MEASUREMENTS: Forty-five patients had a successful repair and 9 did not. Preoperative and intraoperative TVAD in diastole (TVADdiast) ≥4.2 cm, and preoperative systole (TVADsyst) ≥3.7 cm, but not leaflet tethering, were predictive of repair failure. Right ventricular (RV) width >4.88 cm was associated with repair failure. Neither pre- nor post-repair pulmonary artery systolic pressures (PASP) were predictors of repair failure. However, PASP did not change nor did RV function improve in the nonsuccessful repair group. CONCLUSION: For patients with functional TR undergoing primary left heart surgery, preoperative TVAD (systole and diastole), RV width, and postoperative RV function were predictors of repair outcome. Earlier TV repair and optimizing right heart function may improve repair outcome.

Comparison of Clinical and Echocardiographic Outcomes After Surgical Redo Mitral Valve Replacement and Transcatheter Mitral Valve-in-Valve Therapy.

OBJECTIVES: There are minimal data regarding clinical outcomes and echocardiographic findings after transcatheter mitral valve-in-valve replacement (TMVR) compared with redo surgical mitral valve replacement (SMVR). BACKGROUND: TMVR therapy has emerged as therapy for a degenerated bioprosthetic valve failure. METHODS: The authors retrospectively identified patients with degenerated mitral bioprostheses who underwent redo SMVR or TMVR at 3 U.S. institutions. The authors compared clinical and echocardiographic outcomes of patients who had TMVR with those of patients who underwent redo SMVR. RESULTS: Sixty-two patients underwent TMVR and 59 patients underwent SMVR during the study period. Mean age and the Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) scores were significantly higher in patients with TMVR than in those with SMVR (age 74.9 ± 9.4 years vs. 63.7 ± 14.9 years; p < 0.001; STS PROM 12.7 ± 8.0% vs. 8.7 ± 10.1%; p < 0.0001). Total procedure time, intensive care unit hours, and post-procedure length of stay were all significantly shorter in the TMVR group. There was no difference in mortality at 1 year between the 2 groups (TMVR 11.3% vs. SMVR 11.9%; p = 0.92). Mean mitral valve pressure gradient and the grade of mitral regurgitation (MR) were similar between the TMVR group and the SMVR group (mitral valve pressure gradient 7.1 ± 2.5 mm Hg vs. 6.5 ± 2.5 mm Hg; p = 0.42; MR [≥moderate] 3.8% vs. 5.6%; p = 1.00) at 30 days. At 1 year, the mitral valve pressure gradient was higher in the TMVR group (TMVR 7.2 ± 2.7 vs. SMVR 5.5 ± 1.8; p = 0.01), although there was no difference in the grade of MR. CONCLUSIONS: Despite the higher STS PROM in TMVR patients, there was no difference in 1-year mortality between the TMVR and SMVR groups. Echocardiographic findings after TMVR were similar to SMVR at 30 days. There was a statistically significant difference in mitral gradient at 1 year, though this is likely not clinically important. TMVR may be an alternative to SMVR in patients with previous mitral bioprosthetic valves.

Cryoglobulinemic membranoproliferative glomerulonephritis associated with mucosa-associated lymphoid tissue lymphoma treated with rituximab.

Cryoglobulinemia and mucosa-associated lymphoid tissue (MALT) lymphoma are diseases characterized by B-cell dysregulation and overproduction of antibodies. Vasculitis and cutaneous manifestations are common, but renal involvement is rare. A 65-year-old woman with type 1 cryoglobulinemia and MALT lymphomas of the right lacrimal and parotid glands successfully treated by excision and chemoradiotherapy, presented with dyspnea on exertion, edema, and hematuria. Renal biopsy findings revealed type 1 cryoglobulinemic glomerulonephritis. She underwent treatment with high-dose oral prednisone and intravenous rituximab with subsequent return of creatinine to baseline levels. To our knowledge, this is the first report of a patient in whom type 1 cryoglobulinemia, multiple MALT lymphomas, and MPGN with IgM cryoglobulin deposits coexist. Evidence for rituximab is sparse with widely varying protocols and mixed results. There is a need for high quality evidence in the treatment of these conditions.

Formulary review of 2 new biologic agents: tocilizumab for rheumatoid arthritis and ustekinumab for plaque psoriasis.

BACKGROUND: Two autoimmune biologics were recently approved by the FDA: ustekinumab in September 2009 for the treatment of moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy and tocilizumab in January 2010 for adult patients with moderate to severe rheumatoid arthritis (RA) who have not responded adequately to 1 or more tumor necrosis factor (TNF) antagonist therapies. Both agents use new mechanisms of action and add to the growing group of autoimmune biologics. OBJECTIVE: To critically review the phase 3 trials for ustekinumab and tocilizumab and provide managed care considerations in the context of the 9 other biologic agents on the market in the United States that are used to treat moderate to severe RA or psoriasis. METHODS: A MEDLINE review was performed for articles published and available through January 2010 using keywords "ustekinumab" and "tocilizumab" with an emphasis on phase 3 trials. The literature search was limited to articles in English, clinical trials, randomized controlled trials, and research conducted in humans. Search results for ustekinumab included 8 articles of which 4 were excluded for not being psoriasis or psoriatic arthritis trials. Search results for tocilizumab included 16 articles of which 8 were excluded for not being RA trials or using biomarkers as primary endpoints. Additional information was obtained from the FDA website. RESULTS: Three phase 3 trials are available for ustekinumab. Ustekinumab demonstrated superior efficacy to placebo in 2 trials for the treatment of psoriasis. In a 12-week trial, ustekinumab 45 milligrams (mg) and 90 mg demonstrated significantly higher rates of 75% improvement in the psoriasis area and severity index (PASI 75) (67.5% and 73.8%, respectively) compared with etanercept (56.8%) in the first phase 3 comparative psoriasis trial between autoimmune biologics (P < 0.05 for both comparisons). In a phase 3 trial of RA patients who had failed prior TNF antagonist therapy, a 20% improvement in signs or symptoms according to the American College of Rheumatology criteria (ACR 20) at week 24 was achieved by significantly more study participants in the tocilizumab 8 mg per kilogram (kg) (50.0%) and 4 mg per kg (30.4%) groups than the placebo group (10.1%, P < 0.001 for both tocilizumab groups compared with placebo). Safety data for ustekinumab are limited to use for less than 2 years, and the prescribing information contains warnings regarding infection and malignancy. Tocilizumab is associated with neutropenia, thrombocytopenia, and elevations in lipids and liver function tests. Tocilizumab has unique adverse events when compared with other autoimmune biologics and requires laboratory testing and careful monitoring. CONCLUSIONS: Ustekinumab and tocilizumab are new additions to the treatment of autoinflammatory disease. The majority of safety data for both agents are from trials lasting 3 to 6 months. Published long-term safety data for tocilizumab are limited to less than 143 patients treated longer than 5 years, and safety data for ustekinumab are scant beyond 2 years of use; therefore, clinicians should exercise caution prior to widespread adoption. The comparative efficacy and safety trial of etanercept and ustekinumab brings important clinical information to decision makers. Tocilizumab is indicated after failure or intolerance to a TNF antagonist and has unique safety concerns. Managed care plans will consider the experience and long-term data of these agents along with efficacy data and cost when establishing management programs such as prior authorization or step therapy.

Association of prescription abandonment with cost share for high-cost specialty pharmacy medications.

BACKGROUND: In 2008, specialty medications accounted for 15.1% of total pharmacy benefit medication spending, and per member expenditures have increased by 11.1% annually from 2004 to 2008 within a commercially insured population of 8 million members. Insurers face increasing pressure to control specialty medication expenditures and to rely on increasing member cost share through creation of a fourth copayment tier within the incentive-based formulary pharmacy benefit system. Data are needed on the influence that member out-of-pocket (OOP) expense may have on prescription abandonment (defined as the patient never actually taking possession of the medication despite evidence of a written prescription generated by a prescriber). OBJECTIVE: To explore the relationship between prescription abandonment and OOP expense among individuals newly initiating high-cost medication therapy with a tumor necrosis factor (TNF) blocker or multiple sclerosis (MS) biologic agent. METHODS: This observational cross-sectional study queried a midwestern and southern U.S. database of 13,172,480 commercially insured individuals to find members with a pharmacy benefit-adjudicated claim for a TNF blocker or MS specialty medication during the period from July 2006 through June 2008. Prescription abandonment was assessed among continuously enrolled members newly initiating TNF blocker or MS therapy. Prescription abandonment was defined as reversal of the adjudicated claim with no evidence of a subsequent additional adjudicated paid claim in the ensuing 90 days. Separate analyses for MS and TNF blocker therapy were performed to assess the association between member OOP expense and abandonment rate using the Cochran-Armitage test for trend and multivariate logistic regression. Members were placed into 1 of the 7 following OOP expense groups per claim: $0-$100, $101-$150, $151-$200, $201-$250, $251-$350, $351-$500, or more than $500. The association of MS or TNF blocker abandonment rate with OOP expense was tested with logistic regression models using the $0-$100 OOP as the reference group and adjusting for age, gender, formulary status, ZIP code-level income and education, earliest specialty medication claim, and methotrexate use for the TNF blocker analysis. RESULTS: Of 2,791 members presenting a prescription to newly initiate high-cost MS therapy, 1,985 (71.1%) of the claims were for a 1-month supply with most of the remainder for a 3-month supply; 2,303 (82.5%) had an OOP expense of $0-$100, and 5.4% had an OOP expense greater than $500. The abandonment rate increased as OOP increased (test for trend, P < 0.001). Members with an OOP expense of $100 or less had an abandonment rate of 5.7%. Among members in all OOP expense groups greater than $200, the abandonment rate was significantly higher, with more than 1 in 4 members abandoning their MS claims (P < 0.001). In the multivariate logistic regression analysis, the abandonment rate became significantly higher at OOP expenses of $201 to $250 compared with an OOP expense of $100 or less (odds ratio [OR] = 7.3, 95% confidence interval [CI] = 3.3- 16.2). The odds ratios ranged between 6.1 and 7.3 for OOP expense groups greater than $200. Of 7,313 members presenting a prescription to newly initiate TNF blocker therapy, 5,809 (79.4%) of claims were for a 1-month supply with most of the remainder for a 3-month supply; 6,123 (83.7%) had an OOP expense of $0-$100 and 5.7% had an OOP expense greater than $500. The abandonment rate increased as OOP expense increased (test for trend, P < 0.001). In the multivariate logistic regression analysis, the TNF blocker medication abandonment rate was significantly higher for all OOP expense groups greater than $100, with abandonment odds ratios of 2.3 to 4.4 for OOP expense between $101 and $500 compared with OOP expense of $0-$100. The odds of abandonment at OOP expense of greater than $500 were 7-fold higher (OR = 7.0, 95% CI = 5.4-9.1). CONCLUSIONS: This is the first study to perform a focused assessment of an association between specialty medication OOP expense and new therapy prescription abandonment. The study found that per claim OOP expenses greater than $100 for TNF blocker medication and greater than $200 for MS medication were associated with increased prescription abandonment. These findings coupled with previous research identifying a negative relationship between OOP expense above $100 per month and adherence, and the commercial insurance market response to fourth-tier OOP expenses, suggests that insurers should consider the impact that specialty OOP expense may have on adherence and member satisfaction. Further prospective research should be performed to confirm these findings and assess the clinical outcomes associated with prescription abandonment.

Rosiglitazone and pioglitazone utilization from January 2007 through May 2008 associated with five risk-warning events.

BACKGROUND: Rosiglitazone was approved by the U.S. Food and Drug Administration (FDA) for type 2 diabetes in 1999. The unique mechanism of action and low risk of hypoglycemia contributed to rapid market uptake of rosiglitazone, but safety concerns became more prominent in 2007. There were 5 major events on 4 calendar days in 2007 regarding safety concerns related to rosiglitazone in certain patients: (1) the May 21, 2007, online release of the rosiglitazone meta-analysis performed by Nissen and Wolski and the FDA safety warning on the same day; (2) the July 30, 2007, conclusion of an FDA advisory committee meeting that rosiglitazone increased cardiac ischemic risk; (3) the August 14, 2007, update of thiazolidinedione (TZD) labels with a black-box warning for heart failure; and (4) the November 14, 2007, update to the warnings and precautions section of the rosiglitazone label for coadministration of nitrate or insulin. OBJECTIVES: To (1) describe TZD (rosiglitazone and pioglitazone) utilization trends from January 1, 2007, continuing through May 2008 amid public announcements of safety concerns and (2) determine the percentage of TZD users who had medical claims indicating increased cardiovascular (CV) risk before and after release (May 21, 2007) of the FDA safety warning and online release of the meta-analysis performed by Nissen and Wolski. METHODS: A retrospective analysis of pharmacy claims was performed from 9 commercial plans with a combined 9 million eligible members, including a 1.4 million-member cohort from 1 of the plans for which medical claims data were available. We evaluated trends in TZD use for each month for the 17-month period from January 1, 2007, through May 31, 2008, including the percentage of TZD users at increased CV risk. In the trend analysis, for each calendar month of 2007, we calculated mean pharmacy claim counts per day per million members for each of the 2 TZD drugs and for a comparison drug, sitagliptin, a new oral hypoglycemic agent in a different class (dipeptidyl-peptidase-IV inhibitors). For the CV risk analysis, we used the database of integrated medical and pharmacy claims for the 1.4 million-member cohort to identify patients with a current days supply of a TZD on May 20, 2007, December 7, 2007, or May 20, 2008. The medical claims for all identified patients were queried back 2 years from May 20, 2007, December 7, 2007, or May 20, 2008, respectively. Rosiglitazone users at increased CV rsk were defined as those with a medical claim with a primary diagnosis for congestive heart failure (CHF; International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 428.xx or 398.91), those with a current supply of nitrate or insulin therapy, or those with ischemic heart disease, including myocardial infarction (MI; ICD-9-CM codes 410.xx through 414.xx, or surgical procedure codes [36.0x through 36.3x for removal of obstruction and insertion of stents, bypass surgery, and revascularization] in the primary diagnosis field). Pioglitazone users at increased risk were identified from medical claims with a CHF diagnosis code. RESULTS: The average number of claims per day per million members in January 2007 was 97.3 for rosiglitazone and 107.2 for pioglitazone. The average number of claims for rosiglitazone per day per million members began to decrease in May 2007, falling to 41.0 in December 2007, for a total decrease of 58.6% from the February 2007 peak (99.1), and fell further to 31.8 in May 2008. Pioglitazone use increased 8.0% from January to June 2007 (107.2 to 115.8) and remained relatively flat through December 2007 (114.6) and through May 2008 (108.9). Sitagliptin claims increased 5-fold, at a consistent rate, from an average of 8.6 claims per day per million members in January 2007 to 43.4 in December 2007, and continued to increase to 48.7, in May 2008. Of the 5,117 rosiglitazone users on May 20, 2007, 1,296 (25.3%) were identified at increased CV risk versus 590 (22.5%) of 2,621 users on December 7, 2007 (P = 0.006), and 336 (21.8%) of 1,541 users in May 2008 (P = 0.005). Of 6,056 pioglitazone users on May 20, 2007, 170 (2.8%) had a CHF diagnosis versus 160 (2.5%) of 6,275 users on December 7, 2007 (P = 0.376), and 122 of 5,998 users in May 2008 (P = 0.006). CONCLUSIONS: Although rosiglitazone utilization per million members declined by more than half in 2007, when CV safety concerns started to emerge, about 1 in 5 rosiglitazone users had elevated CV risk at year-end 2007 and in May 2008. About 3% of pioglitazone users in May 2007 had a diagnosis of CHF in claims history, which declined to 2% in May 2008. Insurers should consider the impact of persistent utilization of TZDs among members with CV risk factors when making formulary decisions.

Utilization, cost trends, and member cost-share for self-injectable multiple sclerosis drugs--pharmacy and medical benefit spending from 2004 through 2007.

BACKGROUND: In 1993, interferon beta-1b became the first of 4 self-injectable multiple sclerosis (MS) drugs to be approved by the U.S. Food and Drug Administration. Initially covered as a medical expense, self-injectable MS drugs are increasingly considered specialty pharmaceuticals and are often covered under the pharmacy benefit. Self-injectable MS drugs are expensive, costing approximately $2,000 per month per patient in 2007. OBJECTIVES: To (1) determine the trends for price and utilization of self-injectable MS drugs, (2) meld medical and pharmacy claims data to capture total health care spending on self-injectable MS drugs, and (3) calculate the out-of-pocket cost-share for members with pharmacy benefits. METHODS: A pharmacy benefits manager with integrated medical claims for approximately 1.8 million commercial members, about 20% of its total of 9 million commercial members, analyzed self-injectable MS pharmacy claims for a 45-month period beginning in January 2004 and ending in September 2007 and integrated medical and pharmacy claims for a 42-month period beginning in January 2004 and ending in June 2007. The 9 million members are beneficiaries of 10 Blue Cross Blue Shield (BCBS) health plans distributed throughout the United States, and the subset of 1.8 million members are enrolled in 1 BCBS health plan in the Northern Plains states. Self-injectable MS drugs were identified using Generic Product Identifier (GPI) codes for the National Drug Code (NDC) numbers on pharmacy claims. Mail order pharmacy claims with up to a 90-day supply were counted as 3 claims, and community pharmacy claims dispensed with up to a 34-day supply were counted as 1 claim. Self-injectable MS drugs were identified from medical claims using Healthcare Common Procedure Coding System (HCPCS) codes: J1595 for glatiramer, J1830 for subcutaneous interferon beta-1b, Q3026 for subcutaneous interferon beta-1a, and Q3025 and J1825 for intramuscular interferon beta-1a. RESULTS: For the approximately 9 million members with data from pharmacy claims only, these 4 self-injectable MS drugs accounted for approximately 1.8% of total pharmacy benefit spending in 2004, 1.9% in 2005, 2.3% in 2006, and 2.4% in 2007. The mean average wholesale price (AWP) per member per month (PMPM) increased by 56.8%, from $1.11 PMPM in the first quarter of 2004 to $1.74 PMPM in the third quarter of 2007. Utilization was flat at about 82-83 claims per 100,000 members per month during the 45-month measurement period. The average annual price increase per unit ranged from 8.9% for interferon beta-1a to 13.3% per year for interferon beta-1b. Members paid a median out-of-pocket cost per pharmacy claim of $15 in 2004, $20 in 2005 and 2006, and $25 in the first 9 months of 2007. For the 1.8 million members with both pharmacy and medical benefit claims, the medical benefit accounted for 2.5% of total spending on MS self-injectables in 2004, 2.0% in 2005 and 2006, and 1.2% in 2007. CONCLUSION: The percentage of all pharmacy expenditures that was attributable to self-injectable MS drugs increased from 1.8% in 2004 to 2.5% in 2007. Nearly all of the increase in spending on self-injectable MS drugs over the nearly 4-year period was attributable to drug price increases because PMPM utilization was essentially unchanged. The median member cost-share was approximately 1% of the total cost of self-injectable MS drugs.