Ventricular arrhythmias and sudden death events following acalabrutinib initiation.

Acalabrutinib, a next-generation Bruton's tyrosine kinase inhibitor (BTKi), associates with dramatic efficacy against B-cell malignancies. Recently, unexplained ventricular arrhythmias (VAs) with next-generation BTKi-therapy have been reported. Yet, whether acalabrutinib associates with VAs in long-term follow-up is unknown. Leveraging a large-cohort of 290 consecutive B-cell malignancy patients treated with acalabrutinib from 2014 to 2020, we assessed the incidence of VAs. The primary-endpoint was incident VA development (ventricular fibrillation, ventricular tachycardia, and symptomatic premature ventricular contractions). Probability-scores were assessed to determine likelihood of acalabrutinib-association. Incident rates as function of time-on-therapy were calculated. Weighted average observed incidence rates were compared with expected population rates using relative-risks. Absolute excess risk (AER) for acalabrutinib-associated VAs was estimated. Over 1063 person-years of follow-up, there were 8 cases of incident-VAs, including 6 in those without coronary disease (CAD) or heart failure (HF) and 1 sudden-death; median time-to-event 14.9 months. Among those without prior ibrutinib-use, CAD, or HF, the weighted average incidence was 394 per 100 000 person years compared with a reported incidence of 48.1 among similar-aged non-BTKi-treated subjects (relative risk, 8.2; P < .001; AER, 346). Outside of age, no cardiac or electrocardiographic variables associated with VA development. Collectively, these data suggest VAs may be a class-effect of BTKi therapies.

Prognostic relevance of circulating lymphoma cells at diagnosis in newly diagnosed follicular lymphoma patients.

Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma. Circulating lymphoma (CL) cells can be seen at diagnosis in some FL patients, however, previous studies evaluating this have shown mixed results. Therefore, we sought to evaluate the impact of CL at diagnosis on outcomes in patients with newly diagnosed FL using data from a single center. Patients were divided into CL+ and CL- based on immunophenotyping via peripheral blood (PB) flow cytometry. CL was defined as detectable clonally restricted B-cells that matched the actual or expected B-cell immunophenotype of FL. The primary endpoint was progression-free survival (PFS) after first-line treatment and secondary endpoints included overall response rate (ORR), overall survival (OS), diagnosis to treatment interval (DTI), progression of disease within 2 years of diagnosis (POD24), and cumulative incidence of transformation between the two groups. Among the 541 patients with FL, 204 had PB flow cytometry performed at diagnosis, and after excluding patients not meeting the eligibility criteria, 147 cases remained with 24 (16%) CL+ at diagnosis. Patients in the CL+ group were younger (53 vs. 58 years, p = 0.02), had more extranodal involvement (83% vs. 44%, p < 0.01), follicular lymphoma international prognostic index 3-5 (55% vs. 31%, p = 0.01), and a higher proportion received first-line immunochemotherapy (75% vs. 43%, p = 0.01) compared to the CL-group. The median PFS was not significantly different between CL+ (6.27 years, 95% CI = 3.61-NR) and CL- (6.61 years, 95% CI = 5.10-9.82) cohorts regardless of the first-line treatment or level of absolute PB CL cells. There was no significant difference in ORR, median OS, DTI, POD24, and cumulative incidence of transformation between the two groups. In our study, we found that the presence of CL cells at diagnosis in FL in the contemporary era did not impact outcomes and survival.

Post-relapse survival in Waldenstrom macroglobulinemia patients experiencing therapy failure following autologous transplantation.

Waldenström macroglobulinemia (WM) is a rare B-cell lymphoproliferative malignancy. Autologous hematopoietic cell transplantation (auto-HCT) is considered in a subset of WM patients with relapsed disease. While registry data has shown a benefit for auto-HCT in relapsed WM, there is a paucity of data on outcomes of patients relapsing after auto-HCT. Eligibility criteria included adult patients with relapsed/refractory WM who underwent auto-HCT between 2007 and 2017. The primary endpoint was post-relapse overall survival (PR-OS). Secondary endpoints were to identify factors prognostic of PR-OS. Of the 48 patients with WM who underwent auto-HCT, 22 (46%) experienced relapse following auto-HCT. Median PR-OS of relapsed WM patients after auto-HCT (n = 22) was not reached (NR) (95% confidence interval [CI]: 17.5 months-NR). Among patients who relapsed <1 year versus ≥1 year from auto-HCT, the median PR-OS was 18.4 months (95%CI: 0.8-NR) months and NR (95%CI: 17.5-NR), respectively (p = 0.06). Of note, disease status at the time of transplant, CR/VGPR versus partial remission did not appear to impact PR-OS. The median PR-OS was significantly longer in patients who received ibrutinib in the post-transplant setting compared to those who did not (NR vs. 18.4 months, 95%CI: 9.1-NR, p = 0.02). On univariable analysis, the presence of complex karyotype (RR = 4.87, 95% CI = 1.22-19.53) and a higher number of prior lines of therapy (RR = 1.81, 95% CI = 1.23-2.67) were associated with a significantly higher risk of relapse. This is the only study to date that evaluated outcomes of WM patients who relapsed following auto-HCT and provides a benchmark for future trials evaluating survival following auto-HCT relapse.

Developmental subtypes assessed by DNA methylation-iPLEX forecast the natural history of chronic lymphocytic leukemia.

Alterations in global DNA methylation patterns are a major hallmark of cancer and represent attractive biomarkers for personalized risk stratification. Chronic lymphocytic leukemia (CLL) risk stratification studies typically focus on time to first treatment (TTFT), time to progression (TTP) after treatment, and overall survival (OS). Whereas TTFT risk stratification remains similar over time, TTP and OS have changed dramatically with the introduction of targeted therapies, such as the Bruton tyrosine kinase inhibitor ibrutinib. We have shown that genome-wide DNA methylation patterns in CLL are strongly associated with phenotypic differentiation and patient outcomes. Here, we developed a novel assay, termed methylation-iPLEX (Me-iPLEX), for high-throughput quantification of targeted panels of single cytosine guanine dinucleotides from multiple independent loci. Me-iPLEX was used to classify CLL samples into 1 of 3 known epigenetic subtypes (epitypes). We examined the impact of epitype in 1286 CLL patients from 4 independent cohorts representing a comprehensive view of CLL disease course and therapies. We found that epitype significantly predicted TTFT and OS among newly diagnosed CLL patients. Additionally, epitype predicted TTP and OS with 2 common CLL therapies: chemoimmunotherapy and ibrutinib. Epitype retained significance after stratifying by biologically related biomarkers, immunoglobulin heavy chain mutational status, and ZAP70 expression, as well as other common prognostic markers. Furthermore, among several biological traits enriched between epitypes, we found highly biased immunogenetic features, including IGLV3-21 usage in the poorly characterized intermediate-programmed CLL epitype. In summary, Me-iPLEX is an elegant method to assess epigenetic signatures, including robust classification of CLL epitypes that independently stratify patient risk at diagnosis and time of treatment.

Prognostic significance of translocations in the presence of mutated IGHV and of cytogenetic complexity at diagnosis of chronic lymphocytic leukemia.

Mutations of the IGH variable region in patients with chronic lymphocytic leukemia (CLL) are associated with a favorable prognosis. Cytogenetic complexity (>3 unrelated aberrations) and translocations have been associated with an unfavorable prognosis. While mutational status of IGHV is stable, cytogenetic aberrations frequently evolve. However, the relationships of these features as prognosticators at diagnosis are unknown. We examined the CpG-stimulated metaphase cytogenetic features detected within one year of diagnosis of CLL and correlated these features with outcome and other clinical features including IGHV. Of 329 untreated patients, 53 (16.1%) had a complex karyotype (16.1%), and 85 (25.8%) had a translocation. Median time to first treatment (TFT) was 47 months. In univariable analyses, significant risk factors for shorter TFT (p3.5, log-transformed WBC, unmutated IGHV, complex karyotype, translocation, and FISH for trisomy 8, del(11q) and del(17p). In multivariable analysis, there was significant effect modification of IGHV status on the relationship between translocation and TFT (p=0.002). In IGHV mutated patients, those with a translocation had over 3.5 times higher risk of starting treatment than those without a translocation (p.

Intrauterine device use, sexually transmitted infections, and fertility: a prospective cohort study.

BACKGROUND: In the 1970s, numerous medical reports, media coverage, and litigation around the Dalkon Shield intrauterine device led to a perception that all intrauterine devices cause upper genital tract infection and infertility. OBJECTIVE: This study aimed to assess the association between intrauterine device use and time to conception. STUDY DESIGN: The Fertility After Contraceptive Termination Study is a multicenter, prospective cohort study of women stopping their contraceptive method to attempt conception. We recruited participants between 2011 and 2017. Participants were a convenience sample of women recruited from academic centers in Philadelphia, PA; Los Angeles, CA; St. Louis, MO; Indianapolis, IN; Aurora, CO; and Salt Lake City, UT. Women were eligible if they stopped their contraceptive method within the past 120 days before enrollment, were between 18 and 35 years of age, had no history of infertility or sterilization, and had at least 6 months of follow-up. Baseline data included demographic and reproductive characteristics, past contraceptive use, nucleic acid amplification testing for sexually transmitted infections, and serology for past infection with Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma genitalium. The primary exposure was intrauterine device use (ever); the primary outcome was time to conception. All participants were observed longitudinally for up to 24 months. We used piecewise exponential proportional hazards models with multiple imputation to provide hazard ratios and their respective 95% confidence intervals. RESULTS: Of the 461 participants, mean age was 28.2 years, 178 (38.7%) were Black, 157 (34.1%) were considered as low socioeconomic status, and 275 (59.7%) had a history of intrauterine device use. Without adjusting for any covariates, the median time to conception was shorter for participants who had a history of intrauterine device use (5.1 months) than participants who never used an intrauterine device (7.5 months). After controlling for potential confounders, the association of past intrauterine device use with time to conception was not statistically significant (adjusted hazard ratio, 1.25; 95% confidence interval, 0.99-1.58). In our multivariable model, age, nulligravidity, Black race, low socioeconomic status, and past Mycoplasma genitalium infection were associated with longer times to conception (hazard ratio, 0.76; 95% confidence interval, 0.58-0.99). Conception by 12 months was lower in participants with past Mycoplasma genitalium infection (68% vs 80% without past infection; P=.019). CONCLUSION: We found no impairment of fertility with ever use of an intrauterine device. Serologic evidence of past Mycoplasma genitalium infection was associated with longer times to conception and higher rates of infertility. Mycoplasma genitalium infection is a potential modifiable cause of infertility.

Lenalidomide and Vorinostat Maintenance after Autologous Transplantation in Multiple Myeloma: Long- Term Follow-Up.

Post-autologous stem cell transplantation (ASCT) maintenance therapy with lenalidomide is standard of care for patients with multiple myeloma (MM). Effective and tolerable drug combinations may further enhance the clinical response post-ASCT. Vorinostat, a histone deacetylase inhibitor, induces antiproliferative and proapoptotic effects in patients with MM. We hypothesized that combination maintenance therapy would further prolong the clinical response achieved from transplantation. We previously reported that the combination of lenalidomide and vorinostat as maintenance post-ASCT was tolerable in 16 patients with MM. We now present the long-term follow up of these patients. Progression-free survival (PFS) and overall survival (OS) outcomes were characterized using the Kaplan-Meier method. Five patients (31%) had high-risk disease, and the median number of lines of therapy before ASCT was 1 (range, 1 to 5). With a median follow-up of 89.8 months from ASCT, the median PFS was 64.3 months (range, 21.7 months to not reached [NR]), and OS was not reached (median, 53.0 months to NR). At the time of this report, 5 patients remained on the study. The combination of vorinostat and lenalidomide as maintenance post-ASCT is tolerable and induces a durable response. A phase III randomized study of lenalidomide versus a combination with vorinostat is warranted.

Preclinical activity and a pilot phase I study of pacritinib, an oral JAK2/FLT3 inhibitor, and chemotherapy in FLT3-ITD-positive AML.

Activating FLT3 internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) associate with inferior outcomes. We determined that pacritinib, a JAK2/FLT3 inhibitor, has in vitro activity against FLT3-ITD and tyrosine kinase domain (TKD) mutations. Therefore, we conducted a phase I study of pacritinib in combination with chemotherapy in AML patients with FLT3 mutations to determine the pharmacokinetics and preliminary toxicity and clinical activity. Pacritinib was administered at a dose of 100 mg or 200 mg twice daily following a 3 + 3 dose-escalation in combination with cytarabine and daunorubicin (cohort A) or with decitabine induction (cohort B). A total of thirteen patients were enrolled (five in cohort A; eight in cohort B). Dose limiting toxicities include hemolytic anemia and grade 3 QTc prolongation in two patients who received 100 mg. Complete remission was achieved in two patients in cohort A, one of whom had a minor D835Y clone at baseline. One patient in cohort B achieved morphologic leukemia free state. Seven patients (two in cohort A; five in cohort B) had stable disease. In conclusion, pacritinib, an inhibitor of FLT3-ITD and resistant-conferring TKD mutations, was well tolerated and demonstrated preliminary anti-leukemic activity in combination with chemotherapy in patients with FLT3 mutations.

Comparison of Two Doses of Antithymocyte Globulin in Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation.

The appropriate dose of antithymocyte globulin (ATG) to be used in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) is yet to be determined. We retrospectively analyzed the outcomes of patients who underwent unrelated or mismatch related RIC allo-HSCT for hematologic malignancies and received r-ATG (4.5 mg/kg, 141 patients) versus R-ATG (6 mg/kg, 216 patients). There was a higher incidence of cytomegalovirus (P < .001) and Epstein-Barr virus viremia (P =.03) in the R-ATG group than in the r-ATG group. The cumulative incidences of acute graft-versus-host disease (aGVHD) grades II to IV at day 180 in the r-ATG and R-ATG groups were 59% and 44% (P = .006) and grades III to IV 20% and 12% (P = .029), respectively. In multivariable models adjusting for disease diagnosis, the risk of aGVHD grades III to IV did not reach statistical significance (P = .087). The respective cumulative incidences of chronic GVHD in the r-ATG and R-ATG groups were 26% and 15% (P = .10), respectively. There were no significant differences in relapse rate (P = .24), nonrelapse mortality (P = .96), progression-free survival (P = .24), overall survival (P = .70), and GVHD-free relapse-free survival (P = .24). In this retrospective analysis, aGVHD incidence was higher in those treated with r-ATG compared with R-ATG, but this did not translate into significant differences of clinical outcome. Given the increasing use of RIC allo-HSCT for treating malignant hematologic conditions, the correct dose and schedule of ATG administration should be defined by prospective randomized controlled trials.

BEAM versus BUCYVP16 Conditioning before Autologous Hematopoietic Stem Cell Transplant in Patients with Hodgkin Lymphoma.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (AHSCT) is a standard of care for patients with relapsed Hodgkin lymphoma. Different conditioning regimens before AHSCT have been used, with the 2 most common being BEAM (carmustine, etoposide, cytarabine, and melphalan) and BUCYVP16 (busulfan, cyclophosphamide, and etoposide). We retrospectively compared the outcomes of patients treated with BEAM (n = 128) or BUCYVP16 (n = 105) followed by AHSCT. After a median follow-up of 4.2 years for BEAM and 3.8 for BUCYVP16 from AHSCT, the 5-year cumulative incidence of relapse was 29% with BEAM compared with 56% with BUCYVP16 (P < .001). Median progression free survival (PFS) and overall survival (OS) were not reached with BEAM and were 2.0 and 7.8 years with BUCYVP16, respectively. Improved PFS (P < .001) and OS (P = .001) were observed with BEAM for patients who needed transplant within 24 months from diagnosis and for patients not in complete remission (non-CR; P = .001 and P < .001, respectively) at AHSCT. In this large retrospective comparison the use of BEAM conditioning before AHSCT resulted in a statistically significant improved PFS and OS and lower relapse compared with BUCYVP16. This supports the use of BEAM as a frontline conditioning regimen before AHSCT for early relapsed and non-CR Hodgkin lymphoma.

Effect of baseline menstrual bleeding pattern on copper intrauterine device continuation.

BACKGROUND: Heavy menstrual bleeding is a leading cause of copper intrauterine device discontinuation. Thus, girls and women with heavy baseline menstrual bleeding may be at increased risk for early copper intrauterine device discontinuation. OBJECTIVE: Our objective was to assess if there was an association between baseline menstrual bleeding pattern prior to intrauterine device insertion and discontinuation rate at 12 months among study participants who chose copper intrauterine device at baseline. STUDY DESIGN: We performed a secondary analysis of the Contraceptive CHOICE Project, a prospective observational cohort study of 9256 girls and women offered no-cost contraception for 2-3 years. Included in our study were participants who chose copper intrauterine device for contraception and for whom method continuation data at 12 months were available. Prior to contraception initiation, participants were asked to qualify their menstrual bleeding over the past year as: light, moderate, moderately heavy, or heavy. Light bleeding corresponded to using ≤10 pads/tampons per period. Moderate, moderately heavy, and heavy bleeding corresponded to 11-20 pads/tampons, 21-30 pads/tampons, and >30 pads/tampons per period, respectively. Subjects were then categorized into either a "heavy" baseline group (those reporting moderately heavy or heavy bleeding at baseline), or a "not heavy" group (those reporting light or moderate bleeding). The 12-month continuation rate for each group was then calculated using Kaplan-Meier survival function, and hazard ratio for risk of discontinuation was evaluated using a Cox proportional hazard model to determine if moderately heavy or heavy bleeding at baseline was associated with early discontinuation. RESULTS: Of the 918 girls and women meeting the inclusion criteria for this analysis, 165 were in the heavy baseline bleeding group, while 753 were in the not heavy bleeding group. The 12-month continuation rates for groups were similar: 80.2% (heavy) and 85.0% (not heavy; P = .24). Patients reporting either moderately heavy or heavy baseline bleeding were not at increased risk for early discontinuation of copper intrauterine device (hazard ratio, 1.21; 95% confidence interval, 0.88-1.66). Our sample size provided >90% power to detect a clinically important difference of 15% (assuming 20% discontinuation rate in not heavy bleeding group and a 35% discontinuation rate in the heavy bleeding group). CONCLUSION: We did not find that girls and women who reported baseline moderately heavy or heavy menstrual bleeding were at increased risk for early discontinuation. Thus, we do not believe that girls and women with heavy menstrual bleeding should be discouraged from using this safe and highly effective form of contraception.

Anticipated pain as a predictor of discomfort with intrauterine device placement.

BACKGROUND: Intrauterine devices have been gaining popularity for the past 2 decades. Current data report that >10% of women who use contraception are using an intrauterine device. With <1% failure rates, the intrauterine device is one of the most effective forms of long-acting reversible contraception, yet evidence shows that fear of pain during intrauterine device placement deters women from choosing an intrauterine device as their contraceptive method. OBJECTIVES: The objective of this analysis was to estimate the association between anticipated pain with intrauterine device placement and experienced pain. We also assessed other factors associated with increased discomfort during intrauterine device placement. We hypothesized that patients with higher levels of anticipated pain would report a higher level of discomfort during placement. STUDY DESIGN: We performed a secondary analysis of the Contraceptive CHOICE Project. There were 9256 patients enrolled in Contraceptive CHOICE Project from the St. Louis region from 2007-2011; data for 1149 subjects who came for their first placement of either the original 52-mg levonorgestrel intrauterine system or the copper intrauterine device were analyzed in this study. Patients were asked to report their anticipated pain before intrauterine device placement and experienced pain during placement on a 10-point visual analog scale. We assessed the association of anticipated pain, patient demographics, reproductive characteristics, and intrauterine device type with experienced pain with intrauterine device placement. RESULTS: The mean age of Contraceptive CHOICE Project participants in this subanalysis was 26 years. Of these 1149 study subjects, 44% were black, and 53% were of low socioeconomic status. The median expected pain score was 5 for both the levonorgestrel intrauterine system and the copper intrauterine device; the median experienced pain score was 5 for the levonorgestrel intrauterine system and 4 for the copper intrauterine device. After we controlled for parity, history of dysmenorrhea, and type of intrauterine device, higher anticipated pain was associated with increased experienced pain (adjusted relative risk for 1 unit increase in anticipated pain, 1.19; 95% confidence interval, 1.14-1.25). Nulliparity, history of dysmenorrhea, and the hormonal intrauterine device (compared with copper) also were associated with increased pain with intrauterine device placement. CONCLUSION: High levels of anticipated pain correlated with high levels of experienced pain during intrauterine device placement. Nulliparity and a history of dysmenorrhea were also associated with greater discomfort during placement. This information may help guide and treat patients as they consider intrauterine device placement. Future research should focus on interventions to reduce preprocedural anxiety and anticipated pain to potentially decrease discomfort with intrauterine device placement.

Dual method use among long-acting reversible contraceptive users.

OBJECTIVE: To compare rates of dual method use (concurrent use of condoms and an effective method of contraception) in long-acting reversible contraceptive (LARC) and non-LARC hormonal contraceptive users, and to determine factors associated with dual method use. METHODS: We conducted a secondary analysis of the Contraceptive CHOICE Project, an observational, prospective cohort study of 9256 women in St. Louis, MO, USA. Our sample included 6744 women who initiated a contraceptive method within 3 months of enrollment, continued use at 6 months post-enrollment, and responded regarding dual method use. Our primary outcome was the rate of dual method use at 6 months post-enrollment. RESULTS: Dual method use was reported by 32% of LARC and 45% of non-LARC hormonal contraceptive users (p < .01). After adjusting for other covariates and comparing to non-LARC hormonal contraceptive users, LARC users were less likely to report dual method use (RRadj 0.76, 95% CI 0.70-0.83). Factors associated with dual method use in our multivariable analysis were age <25 years, black race, lower education, single relationship status, baseline dual method use, baseline diagnosis of sexually transmitted infection (STI), greater partner willingness to use a condom, and higher condom self-efficacy score. CONCLUSIONS: LARC users are less likely to report dual method use compared to non-LARC hormonal contraceptive users, but other factors also impact dual method use. Further studies should be performed to determine whether this lower dual method use increases the risk of STI. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov Identifier NCT01986439.

Provision of no-cost, long-acting contraception and teenage pregnancy.

BACKGROUND: The rate of teenage pregnancy in the United States is higher than in other developed nations. Teenage births result in substantial costs, including public assistance, health care costs, and income losses due to lower educational attainment and reduced earning potential. METHODS: The Contraceptive CHOICE Project was a large prospective cohort study designed to promote the use of long-acting, reversible contraceptive (LARC) methods to reduce unintended pregnancy in the St. Louis region. Participants were educated about reversible contraception, with an emphasis on the benefits of LARC methods, were provided with their choice of reversible contraception at no cost, and were followed for 2 to 3 years. We analyzed pregnancy, birth, and induced-abortion rates among teenage girls and women 15 to 19 years of age in this cohort and compared them with those observed nationally among U.S. teens in the same age group. RESULTS: Of the 1404 teenage girls and women enrolled in CHOICE, 72% chose an intrauterine device or implant (LARC methods); the remaining 28% chose another method. During the 2008-2013 period, the mean annual rates of pregnancy, birth, and abortion among CHOICE participants were 34.0, 19.4, and 9.7 per 1000 teens, respectively. In comparison, rates of pregnancy, birth, and abortion among sexually experienced U.S. teens in 2008 were 158.5, 94.0, and 41.5 per 1000, respectively. CONCLUSIONS: Teenage girls and women who were provided contraception at no cost and educated about reversible contraception and the benefits of LARC methods had rates of pregnancy, birth, and abortion that were much lower than the national rates for sexually experienced teens. (Funded by the Susan Thompson Buffett Foundation and others.).

Condom use and incident sexually transmitted infection after initiation of long-acting reversible contraception.

BACKGROUND: Use of more effective contraception may lead to less condom use and increased incidence of sexually transmitted infection. OBJECTIVE: The objective of this study was to compare changes in condom use and incidence of sexually transmitted infection acquisition among new initiators of long-acting reversible contraceptives to those initiating non-long-acting reversible contraceptive methods. STUDY DESIGN: This is a secondary analysis of the Contraceptive CHOICE Project. We included 2 sample populations of 12-month continuous contraceptive users. The first included users with complete condom data (baseline, and 3, 6, and 12 months) (long-acting reversible contraceptive users: N = 2371; other methods: N = 575). The second included users with 12-month sexually transmitted infection data (long-acting reversible contraceptive users: N = 2102; other methods: N = 592). Self-reported condom use was assessed at baseline and at 3, 6, and 12 months following enrollment. Changes in condom use and incident sexually transmitted infection rates were compared using χ2 tests. Risk factors for sexually transmitted infection acquisition were identified using multivariable logistic regression. RESULTS: Few participants in either group reported consistent condom use across all survey time points and with all partners (long-acting reversible contraceptive users: 5.2%; other methods: 11.3%; P < .001). There was no difference in change of condom use at 3, 6, and 12 months compared to baseline condom use regardless of method type (P = .65). A total of 94 incident sexually transmitted infections were documented, with long-acting reversible contraceptive users accounting for a higher proportion (3.9% vs 2.0%; P = .03). Initiation of a long-acting reversible contraceptive method was associated with increased sexually transmitted infection incidence (odds ratio, 2.0; 95% confidence ratio, 1.07-3.72). CONCLUSION: Long-acting reversible contraceptive initiators reported lower rates of consistent condom use, but did not demonstrate a change in condom use when compared to preinitiation behaviors. Long-acting reversible contraceptive users were more likely to acquire a sexually transmitted infection in the 12 months following initiation.

Risk of unintended pregnancy based on intended compared to actual contraceptive use.

BACKGROUND: After initiating a new contraceptive method, the provider has little control of how or whether that method is used. OBJECTIVE: We sought to compare unintended pregnancy rates by the initial chosen contraceptive method after counseling to traditional contraceptive effectiveness in the same study population. STUDY DESIGN: The Contraceptive CHOICE Project provided reversible contraception to 9252 women at no cost during 2-3 years of follow-up. We performed 2 analyses of contraceptive efficacy in this prospective cohort: (1) intent-to-use (ITU), grouping participants based on their chosen method at enrollment; and (2) as-used, categorizing participant time according to the method used. In ITU analysis, switching of methods and method continuation were not considered, as we wanted to assess outcomes based on the method chosen at baseline. We used Cox proportional hazards models to compare rates of unintended pregnancy. RESULTS: During 20,017 person-years, we identified 615 unintended pregnancies. In ITU analysis, pregnancy rates were 5.3, 5.5, 2.0, 1.7, and 1.9 per 100 person-years for women initiating oral, injectable, implantable, copper, and hormonal intrauterine contraception (IUC) at baseline, respectively. The adjusted hazard ratio for injectable contraception compared to hormonal IUC was 2.4 (95% confidence interval, 1.8-3.3). Delaying initiation of IUC or implantable contraception increased unintended pregnancies by 60% (adjusted hazard ratio, 1.6; 95% confidence interval, 1.2-2.0). In as-used analysis, pregnancy rates were 6.7, 1.6, 0.2, 0.6, and 0.2 per 100 person-years for women using oral, injectable, implantable, copper, and hormonal IUC, respectively. CONCLUSION: Although highly effective in the as-used analysis, women initially choosing injectable contraception had pregnancy rates similar to oral contraception and significantly worse than IUC or implantable contraception. Despite switching and discontinuation, women choosing an IUC or implantable contraception at baseline were much less likely to have an unintended pregnancy compared to those selecting other methods.