Belimumab use during pregnancy: Interim results of the belimumab pregnancy registry.

BACKGROUND: Belimumab is approved for active, autoantibody-positive systemic lupus erythematosus (SLE) and lupus nephritis, but limited data exist regarding its use in pregnancy. The Belimumab Pregnancy Registry (BPR, GSK Study BEL114256; NCT01532310) was created to evaluate pregnancy and infant outcomes following belimumab exposure. METHODS: Individuals with SLE exposed to belimumab from 4 months before and/or during pregnancy can enroll into the BPR. The primary outcome is major birth defects; secondary outcomes include miscarriages, stillbirths, elective termination, pre-term birth, neonatal death, small for gestational age, and adverse infant outcomes during the first year of life. Belimumab exposure timing, concomitant medications, and other potential confounding factors are also collected. Data up to March 8, 2021, are reported descriptively. RESULTS: From an expected sample size target of 500 prospective pregnancies with a known outcome, only 55 were enrolled in the study. Among these, two pregnancy losses and 53 pregnancies with a live birth outcome were reported. Ten of the 53 live birth pregnancies resulted in a major birth defect. Ten pregnancies were enrolled after the pregnancy outcome occurred and were examined retrospectively (four live births with no defects, four miscarriages, and two elective terminations). There was no indication or pattern of birth defects associated with belimumab. CONCLUSIONS: Low recruitment numbers for the BPR and incomplete information limit the conclusions regarding belimumab exposure during pregnancy. There was no pattern or common mechanism of birth defects associated with belimumab within the BPR data.

Belimumab use during pregnancy: a summary of birth defects and pregnancy loss from belimumab clinical trials, a pregnancy registry and postmarketing reports.

OBJECTIVE: Describe available data on birth defects and pregnancy loss in women with systemic lupus erythematosus (SLE) exposed to belimumab. METHODS: Data collected from belimumab clinical trials, the Belimumab Pregnancy Registry (BPR), and postmarketing/spontaneous reports up to 8 March 2020 were described. Belimumab exposure timing, concomitant medications and potential confounding factors were summarised descriptively. RESULTS: Among 319 pregnancies with known outcomes (excluding elective terminations), 223 ended in live births from which birth defects were identified in 4/72 (5.6%) in belimumab-exposed pregnancies and 0/9 placebo-exposed pregnancies across 18 clinical trials, 10/46 (21.7%) belimumab-exposed pregnancies in the BPR prospective cohort (enrolled prior to pregnancy outcome) and 0/4 belimumab-exposed pregnancies in the BPR retrospective cohort (enrolled after pregnancy outcome), and 1/92 (1.1%) in belimumab-exposed pregnancies from postmarketing/spontaneous reports. There was no consistent pattern of birth defects across datasets. Out of pregnancies with known outcomes (excluding elective terminations), pregnancy loss occurred in 31.8% (35/110) of belimumab-exposed women and 43.8% (7/16) of placebo-exposed women in clinical trials; 4.2% (2/48) of women in the BPR prospective cohort and 50% (4/8) in the BPR retrospective cohort; and 31.4% (43/137) of belimumab-exposed women from postmarketing/spontaneous reports. All belimumab-exposed women in clinical trials and the BPR received concomitant medications and had confounding factors and/or missing data. CONCLUSIONS: Observations reported here add to limited data published on pregnancy outcomes following belimumab exposure. Low numbers of exposed pregnancies, presence of confounding factors/other biases, and incomplete information preclude informed recommendations regarding risk of birth defects and pregnancy loss with belimumab use.

Identifying Barriers to Enrollment in Patient Pregnancy Registries: Building Evidence Through Crowdsourcing.

BACKGROUND: Enrollment in pregnancy registries is challenging despite substantial awareness-raising activities, generally resulting in low recruitment owing to limited safety data. Understanding patient and physician awareness of and attitudes toward pregnancy registries is needed to facilitate enrollment. Crowdsourcing, in which services, ideas, or content are obtained by soliciting contributions from a large group of people using web-based platforms, has shown promise for improving patient engagement and obtaining patient insights. OBJECTIVE: This study aimed to use web-based crowdsourcing platforms to evaluate Belimumab Pregnancy Registry (BPR) awareness among patients and physicians and to identify potential barriers to pregnancy registry enrollment with the BPR as a case study. METHODS: We conducted 2 surveys using separate web-based crowdsourcing platforms: Amazon Mechanical Turk (a 14-question patient survey) and Sermo RealTime (a 11-question rheumatologist survey). Eligible patients were women, aged 18-55 years; diagnosed with systemic lupus erythematosus (SLE); and pregnant, recently pregnant (within 2 years), or planning pregnancy. Eligible rheumatologists had prescribed belimumab and treated pregnant women. Responses were descriptively analyzed. RESULTS: Of 151 patient respondents over a 3-month period (n=88, 58.3% aged 26-35 years; n=149, 98.7% with mild or moderate SLE; and n=148, 98% from the United States), 51% (77/151) were currently or recently pregnant. Overall, 169 rheumatologists completed the survey within 48 hours, and 59.2% (100/169) were based in the United States. Belimumab exposure was reported by 41.7% (63/151) patients, whereas 51.7% (75/145) rheumatologists had prescribed belimumab to <5 patients, 25.5% (37/145) had prescribed to 5-10 patients, and 22.8% (33/145) had prescribed to >10 patients who were pregnant or trying to conceive. Of the patients exposed to belimumab, 51% (32/63) were BPR-aware, and 45.5% (77/169) of the rheumatologists were BPR-aware. Overall, 60% (38/63) of patients reported belimumab discontinuation because of pregnancy or planned pregnancy. Among the 77 BPR-aware rheumatologists, 70 (91%) referred patients to the registry. Concerns among rheumatologists who did not prescribe belimumab during pregnancy included unknown pregnancy safety profile (119/169, 70.4%), and 61.5% (104/169) reported their patients' concerns about the unknown pregnancy safety profile. Belimumab exposure during or recently after pregnancy or while trying to conceive was reported in patients with mild (6/64, 9%), moderate (22/85, 26%), or severe (1/2, 50%) SLE. Rheumatologists more commonly recommended belimumab for moderate (84/169, 49.7%) and severe (123/169, 72.8%) SLE than for mild SLE (36/169, 21.3%) for patients trying to conceive recently or currently pregnant. Overall, 81.6% (138/169) of the rheumatologists suggested a belimumab washout period before pregnancy of 0-30 days (44/138, 31.9%), 30-60 days (64/138, 46.4%), or >60 days (30/138, 21.7%). CONCLUSIONS: In this case, crowdsourcing efficiently obtained patient and rheumatologist input, with some patients with SLE continuing to use belimumab during or while planning a pregnancy. There was moderate awareness of the BPR among patients and physicians.

Patient and healthcare professional experiences of the Salford Lung Studies: qualitative insights for future effectiveness trials.

BACKGROUND: Randomized controlled trials (RCTs) conducted in the routine care setting provide the opportunity to better understand the effectiveness of new medicines but can present recruitment difficulties. An improved understanding of the challenges/opportunities for patient and healthcare professional (HCP) engagement in clinical research is needed to enhance participation and trial experience. In this study, we explored patient and HCP drivers for, and experiences of, participation in the Salford Lung Studies (SLS), and their views on future trial participation and the overall value of such trials. METHODS: This was a qualitative study set in Salford, UK, comprising patient telephone interviews (N = 10) and HCP advisory boards (one with general practitioners [GPs], one with practice managers [PMs]); all individuals had participated in the SLS. Semi-structured telephone interviews were recorded, transcribed and analysed thematically. Advisory board meetings were analysed based on transcriptions of audio recordings and field notes. RESULTS: For patients, key positive aspects of the SLS were the ease/convenience of study assessments and excellent relationships with study nurses. GPs and PMs considered the SLS to be well-organized and highlighted the value of research nurse support; they also described minor challenges relating to trial systems, initial financial strain on practices and staff turnover. All participants indicated that they were very likely to participate in future trials, citing a design closely aligned with routine care practice as essential. Several strategies to encourage trial participation were suggested, such as clearly communicating benefits to patients and ensuring flexible study assessments. CONCLUSIONS: Patients and HCPs had positive experiences of the SLS. The study design, closely aligned with routine care, was considered important to their high likelihood of participating in future trials. The experiences of patients and HCPs in the SLS provide valuable insights that will help inform future best practice in the design and conduct of future real-world effectiveness RCTs in primary care. The detailed first-hand experiences of HCPs will be of significant value to others considering engaging in clinical research and participating in effectiveness RCTs.

Real-world mepolizumab in the prospective severe asthma REALITI-A study: initial analysis.

INTRODUCTION: Efficacy of mepolizumab, an anti-interleukin-5 monoclonal antibody, was demonstrated in randomised controlled trials; data on its real-world impact in routine clinical practice are starting to emerge. We assessed the effectiveness and safety of mepolizumab prescribed for patients in the real world. METHODS: REALITI-A is a global, prospective, observational cohort study, collecting data from routine healthcare visits from patients with asthma. Patients newly prescribed mepolizumab for severe asthma with 12 months of relevant medical history pre-mepolizumab (collected retrospectively) were enrolled. An initial analysis of data from early initiators who had completed 1 year of follow-up (as of February 28, 2019) was conducted. The primary objective was to compare the rate of clinically significant exacerbations (requiring oral corticosteroids (OCS) and/or hospitalisation and/or emergency department visit) before and after mepolizumab; exacerbations requiring hospitalisation and/or emergency department visit and change in maintenance OCS use were secondary objectives. Treatment-related adverse events were reported. RESULTS: Overall, 368 mepolizumab-treated patients were included. Rates of clinically significant exacerbations were reduced by 69% from 4.63 per person per year pre-treatment to 1.43 per person per year during follow-up (p<0.001), as were those requiring hospitalisation and/or emergency department visit (from 1.14 to 0.27 per person per year; 77% reduction). In 159 patients with maintenance OCS dose data available during the pre-treatment period, median daily dose decreased from 10.0 (pre-treatment) to 5.0 mg·day-1 by week 21-24 of follow-up, sustained until week 53-56. No new safety signals were reported. CONCLUSION: These data demonstrate that the effectiveness of mepolizumab is consistent with clinical trial results under real-world settings, with significant reductions in exacerbations and daily maintenance OCS dose.