O-132 Sustained efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT 52-week data

Study question To assess the long-term (52-week) efficacy and safety of relugolix combination therapy (Relugolix-CT) in the treatment of endometriosis-associated pain. Summary answer Relugolix-CT demonstrated a sustained improvement of endometriosis-associated pain and maintenance of bone mineral density (BMD) over the extension treatment period. It was well tolerated. What is known already Endometriosis is a chronic condition characterized by symptoms of menstrual and non-menstrual pain, and dyspareunia, which have a substantial impact on women’s lives. SPIRIT 1 and 2 were Phase 3, randomized, double-blind, placebo-controlled studies of once-daily Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) in premenopausal women (age 18–50 years) with surgically diagnosed endometriosis and moderate-to-severe dysmenorrhea and non-menstrual pelvic pain (NMPP) at baseline. These trials demonstrated a significant improvement of dysmenorrhea, NMPP and dyspareunia in women treated with Relugolix-CT, with a minimal decline in BMD vs placebo over 24 weeks. Study design, size, duration Women who completed the 24-week pivotal studies (SPIRIT 1 and 2 trials) were eligible to enroll in an open-label, single-arm, long-term safety and efficacy extension study for an additional 80 weeks. All women received once-daily oral Relugolix-CT. Analyses were done based on original randomization in pivotal studies: Relugolix-CT, delayed Relugolix-CT (relugolix 40 mg alone for 12 weeks, then Relugolix-CT for 12 weeks), or placebo. Here, 52-week efficacy and safety outcomes are presented. Participants/materials, setting, methods The primary endpoints were the proportion of dysmenorrhea and NMPP responders at Week 52, based on daily Numerical Rating Scale (NRS) scores (0=no pain, 10=worst pain imaginable). A responder was a woman who achieved a predefined, clinically meaningful reduction from baseline in NRS score with no increase in analgesic use. Secondary efficacy endpoints included change in Endometriosis Health Profile-30 (EHP-30) pain domain scores, and analgesic/opioid use. Safety endpoints included adverse events (AEs) and BMD evaluation. Main results and the role of chance Of 1261 randomized patients, 1044 completed the primary studies; 802 enrolled in the long-term extension and 681 completed 52 weeks of treatment. Baseline demographics and clinical characteristics of the extension population were consistent with those of the original randomized population. Sustained improvement of endometriosis-associated pain was demonstrated with Relugolix-CT through 52 weeks, the proportion of responders for dysmenorrhea was 84.8% and 73.3% for NMPP. NRS least squares (LS) mean scores for dysmenorrhea and NMPP decreased from 7.4 (severe) and 6.0 (moderate) at SPIRIT study baseline to 1.3 (mild) and 2.2 (mild) at Week 52, equating to 82.8% and 62.9% reduction in dysmenorrhea and NMPP, respectively. Mean NRS for dyspareunia decreased from 5.9 (moderate) to 2.4 (mild), demonstrating 60.1% reduction with Relugolix-CT. Daily functioning measured by the EHP-30 pain domain score was improved (–38.1 point) and the majority of women (85.6%) were opioid-free at Week 52. There was no disproportionate increase in the incidence of AEs in the Relugolix-CT group with no new safety signals identified through the 52 weeks. BMD was preserved over the extension period with overall LS mean change from baseline to Week 52 of –0.83% (95% CI: –1.34, –0.32) for lumbar spine in the Relugolix-CT group. Limitations, reasons for caution The study was conducted as an open-label study without a control group over the 28 weeks of the extension period. Wider implications of the findings Relugolix-CT demonstrated a sustained improvement of dysmenorrhea, NMPP, and dyspareunia, and reduced pain-related functional limitations and the need for opioids over 52 weeks in women with moderate-to-severe endometriosis-associated pain. Relugolix-CT was generally well tolerated and associated with minimal BMD loss after treatment initiation followed by BMD maintenance over 52 weeks. Trial registration number NCT03654274

O-131 The effect of time since surgical diagnosis of endometriosis on treatment outcomes with relugolix combination therapy in women with endometriosis-associated pain: SPIRIT program

Study question To assess the efficacy of Relugolix-CT vs placebo in women who were surgically diagnosed with endometriosis <5 and > = 5 years ago. Summary answer Treatment outcomes did not differ for dysmenorrhea and daily functioning between subgroups of patients with <5 years or ≥ 5 years since surgical diagnosis. What is known already Time since clinical manifestation and diagnosis of endometriosis may influence the treatment success of patients with endometriosis-associated pain. SPIRIT 1 and 2 were randomized, double-blind, placebo-controlled Phase 3 studies of Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) in premenopausal women (age 18–50 years) with surgically diagnosed endometriosis and a history of moderate-to-severe dysmenorrhea and non-menstrual pelvic pain (NMPP). These studies previously demonstrated that Relugolix-CT significantly reduced dysmenorrhea and NMPP, and improved daily functioning measured by the Endometriosis Health Profile-30 (EHP-30) pain domain score vs placebo over 24 weeks. Study design, size, duration Premenopausal women with surgically diagnosed endometriosis and moderate-to-severe dysmenorrhea and NMPP at baseline were randomized 1:1:1 to 24 weeks of treatment with once daily oral Relugolix-CT, delayed Relugolix-CT (relugolix 40 mg monotherapy for 12 weeks followed by Relugolix-CT for 12 weeks), or placebo. The proportion of dysmenorrhea and NMPP responders at Week 24/End-of-Treatment (EoT), based on daily Numerical Rating Scale (NRS), and analgesic use status were co-primary endpoints. Participants/materials, setting, methods Pooled SPIRIT 1 and 2 data of patients who received 24 weeks of treatment with once daily Relugolix-CT (N = 418) or placebo (N = 416) are presented. Outcomes for the delayed Relugolix-CT group were only for the safety assessment and therefore not reported here. Analyses of NRS scores for dysmenorrhea, NMPP, and EHP-30 pain domain score were carried out in the subgroups of patients with time since diagnosis of < 5 years (N = 579) and ≥5 years (N = 255). Main results and the role of chance Baseline demographics and clinical characteristics were comparable between the time since diagnosis subgroups except for a numerically higher mean age in the ≥5-years subgroup. Mean time since diagnosis (standard deviation) was 2.1 (1.5) years with both Relugolix-CT and placebo for <5-years subgroup, and 8.0 (2.8) and 7.8 (2.3) years, respectively, for ≥5-years subgroup. In Relugolix-CT-treated patients, mean NRS score for dysmenorrhea decreased from 7.5 (severe) to 1.8 (mild) in the <5-years subgroup and from 6.9 (moderate) to 1.8 (mild) in the ≥5-years subgroup with a significant difference to placebo (p < 0.0001, both subgroups), and demonstrating 74.8% and 72.7% reduction in pain from baseline to Week 24/EoT, respectively. Mean NRS score for NMPP decreased from 6.0 (moderate) to 3.0 (mild) with a significant difference compared with placebo (p < 0.0001), equating to 48.8% pain reduction in the <5-years subgroup, and from 5.6 (moderate) to 2.7 (mild) equating to 51.5% pain reduction (p = 0.089) in the ≥5-years subgroup. Improvement of daily functioning as measured by EHP-30 pain domain score was significantly greater with Relugolix-CT vs placebo in both subgroups, with decrease in EHP-30 pain score from 59.1 to 24.0 in the <5-years subgroup, and from 57.4 to 21.1 in the ≥5-years subgroup (p < 0.0001, both subgroups). Limitations, reasons for caution A lower number of patients were included into the subgroup with ≥5-years since surgically diagnosed endometriosis. Five-year dichotomy was close to the mean time since surgical diagnosis in the studies and to certain extent is arbitrary. Furthermore, time since surgical diagnosis is not the same as time since symptom onset. Wider implications of the findings In women with endometriosis-associated pain, Relugolix-CT vs placebo significantly reduced dysmenorrhea and improved daily functioning in both groups: with surgical diagnosis of < 5 years or ≥ 5 years. Substantial decrease in NMPP was also observed and was significantly different to placebo in the <5-years subgroup. Trial registration number NCT03204318 and NCT03204331

Manfaat Aromaterapi Jasmine Sambac dalam Meningkatkan Libido pada Akseptor KB Suntik DMPA

Latar Belakang. DMPA adalah kontrasepsi suntik hormonal yang banyak dipakai masyarakat, dengan salah satu efek samping adalah penurunan libido. Salah satu cara mengatasinya adalah dengan menggunakan aromaterapi jasmine sambac. Tujuan. Penelitian ini bertujuan untuk mengujicobakan aromaterapi jasmine sambac untuk meningkatkan libido pada akseptor suntik DMPA di PMB Aini Kabupaten Kudus. Metode. Jenis penelitian ini adalah quasi experiment dengan desain one group pre-test and post-test without control. Sampel dalam penelitian ini adalah 16 akseptor suntik DMPA yang diambil dengan Teknik purposive. Responden menggunakan aromaterapi jasmine sambac dalam bentuk lilin pada malam hari menjelang tidur, dengan durasi 2,5 jam selama 14 hari. Tingkat libido diukur menggunakan kuesioner FSFI. Analisa data menggunakan uji Wilcoxon. Hasil. Rata-rata responden mengalami peningkatan total tingkat libido sebesar 15,8 point. Rata-rata peningkatan perdomain aspeknya adalah keinginan 2,3 point, gairah 2,5 point, lubrikasi 2,6 point, orgasme 2,8 point, kepuasan 2,5 point, dan nyeri 3,2 point. Hasil uji Wilcoxon didapatkan ada perbedaan yang signifikan pada tingkat libido total dan semua domain aspeknya (p value ≤ 0,05). Kesimpulan. Aromaterapi jasmine sambac berpengaruh signifikan dalam meningkatkan total libido, termasuk 6 domain aspeknya, dimana rata-rata peningkatan yang paling banyak adalah pada domain nyeri, dan yang paling sedikit rata-rata peningkatnnya adalah pada domain gairah. Kata Kunci : aromaterapi, jasmine, libido ABSTRACT Background. DMPA is a hormonal injection contraceptive that is widely used by the community, with one of the side effects is a decrease in libido. One way to overcome this problem is to use jasmine sambac aromatherapy. Destination. Objective. To try out the aromatherapy jasmine sambac to increase libido in DMPA injection acceptors in PMB Aini, Kudus Regency. Method. This type of research is a quasi experiment with one group pre-test and post-test designs without control. The sample in this study were 16 DMPA injection acceptors taken by purposive technique. Respondents used jasmine sambac aromatherapy in the form of candles at night before bed, with a duration of 2.5 hours for 14 days. Libido level was measured using the FSFI questionnaire. Data analysis using the Wilcoxon test. Result. The average of respondents experienced an increase in the total level of libido by 15.8 points. The average increase in aspects per domain is 2.3 points of desire, 2.5 points of arousal, 2.6 points of lubrication, 2.8 points of orgasm, 2.5 points of satisfaction, and 3.2 points of pain. The results of the Wilcoxon test showed that there were significant differences in the level of total libido and all domain aspects (p value ≤ 0.05). Conclusion. Jasmine sambac aromatherapy has a significant effect in increasing total libido, including its 6 domain aspects, where the average increase is the most in the pain domain, and the least average increase is in the arousal domain. Keywords: aromatherapy, jasmine, libido

Comparing two dry needling interventions for plantar heel pain: a randomised controlled trial

ObjectivesTo compare the effectiveness of dry needling (DN) versus percutaneous needle electrolysis (PNE) for improving the level of pain, function and quality of life (QoL) of patients suffering from plantar heel pain (PHP) provoked by myofascial trigger points.DesignA prospective, parallel-group, randomised controlled trial with blinded outcome assessment.SettingA single treatment facility in the State of Kuwait.Participants118 participants were screened for eligibility. Of these, 102 participants were enrolled (30 men (49.5±8.9 years) and 72 women (48.1±8.8 years)) and 68 of them completed the trial.InterventionsTwo parallel groups, one study arm received DN and a stretching protocol whereas the other arm received percutaneous needling electrolysis with a stretching protocol.Primary and secondary outcome measuresThe primary outcome measure was the Foot Pain domain of the Foot Health Status Questionnaire, with 13 questions related to foot health-related domains. Secondary outcome measures included the 0–10 numerical rating scale pain visual analogue scale (VAS) scores, performed before and after each treatment session. In addition, QoL was measured using the EuroQoL-5 dimensions. All measurements were taken at baseline, at 4, 8, 12, 26 and 52 weeks.ResultsFoot Pain domain improved at all time points for DN group (p<0.001; 29.7 (17.8 to 41.5)) and percutaneous needling electrolysis group (p<0.001; 32.7 (18.3 to 47.0)), without significant differences between groups. Pain VAS scores decreased at all time points for both DN (p<0.001; −2.6 (−4.0 to −1.2)) and percutaneous needling electrolysis group (p<0.001; −3.0 (−4.5 to −1.6)). QoL improved at 4 weeks for both DN (p<0.01; 0.15 (0.5 to 0.25)) and percutaneous needling electrolysis group (p<0.01; 0.09 (0.01 to 0.17)) and at 8 and 52 weeks for the PNE group (p<0.01; 0.10 (0.02 to 0.18)), with significant differences between groups for the QoL at 52 weeks (p<0.05; 0.10 (0.01 to 0.18)). There were two small haematomas in the PNE group and one in the DN group. No serious adverse events were reported.ConclusionsBoth PNE and DN were effective for PHP management, reducing mean and maximum pain since the first treatment session, with long lasting effects (52 weeks) and significant differences between groups in the case of QoL at 52 weeks in favour of the PNE group.Trial registration numberNCT03236779.

The association of Boswellia resin extract and propolis derived polyphenols can improve quality of life in patients affected by prostatitis-like symptoms

Objectives: Chronic prostatitis syndrome is a bothering and poorly understood condition. Many patients report genitourinary pain and Lower Urinary Tract Symptoms as a main complaint. Many different pharmacological or behavioural therapies are prescribed in daily clinical practice, but efficacy data are still lacking. The aim of our study was to test the efficacy and safety of a transrectal delivered association of Boswellia resin extract and propolis derived polyphenols for the relief of prostatitis - like symptoms. Materials and methods: Patients affected by chronic/recurrent prostatitis - like symptoms were prospectively enrolled in our study from December, 2016 to December, 2018. Patients were screened at baseline through clinical examination and validated questionnaires administration: Chronic Prostatitis Symptom Index (CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF). Inclusion criteria were: age ≥ 18; prostatitis symptoms persisting for at least 3 of the last 6 months; CPSI pain domain score ≥ 5; previous negative Meares-Stamey test. Treatment consisted on the administration of 1 suppository containing Boswellia resin extract and propolis derived polyphenols, once a day for 20 days. The primary endpoint of the study was the improvement of quality of life after treatment, defined by a reduction of ≥ 2 points, or ≥ 25%, of mean CPSI pain domain score, compared to baseline. Secondary endpoints were the improvement of post-treatment CPSI total score and the analysis of treatment - related adverse events. All patients were re-evaluated 1 month after treatment. Results: 40 patients were enrolled in our study. Median age (Inter - Quartile Range IQR) was 51.5 (41.5-63.2) years. Mean baseline CPSI scores were: 22.15 (total score), 9.67 (pain domain), 5.15 (micturition domain) and 7.35 (quality of life domain), respectively. No significant adverse events were reported. At 1 month follow-up, CPSI scores appeared modified as follows: 16.40 (total score, p = 0.001); 6.92 (pain domain; p = 0.001; 4.02 (micturition domain, p = 0.09); 5.45 (quality of life domain, p = 0.002). Mean CPSI pain domain score reduction was -2.75 points (-28.5%). Mean CPSI total score reduction was -5.75 points (-26%). Conclusions: The association of Boswellia resin extract and propolis derived polyphenols can reduce genitourinary pain and then improve quality of life of men affected by bothersome prostatitis - like symptoms.

Validation of the Ankle Osteoarthritis Scale Instrument for Preoperative Evaluation of End-Stage Ankle Arthritis Patients Using Item Response Theory

Background: Significant ankle arthritis results in functional limitations and patient morbidity. There is a need to measure symptoms and the impact of interventions on patient’s quality of life using valid and reliable patient-reported measurement instruments. The objective of this research was to validate the Ankle Osteoarthritis Scale instrument in the preoperative setting using factor analysis, item response theory, and differential item function methods. Methods: This research is based on secondary analysis of patients scheduled for ankle arthrodesis or total ankle replacement in Vancouver, Canada. Participants completed the instrument between September 2014 and August 2017. Item response theory was used to estimate item difficulty and discrimination parameters, controlling for study participants’ underlying level of ankle function. Differential item function was examined for sex, age group, and surgery. There were 88 participants. Results: Modification indices suggested that item 10, “walking around the house,” would better fit the pain domain rather than the disability domain. Items in the pain domain displayed a range of discrimination and difficulty. Items in the disability domain exhibited a range of discrimination, though the disability domain had low difficulty. Differential item functioning for sex, age group, and ankle arthrodesis or total ankle replacement appeared to be ignorable. Conclusion: This evaluation of the Ankle Osteoarthritis Scale found the instrument to be a strong measure of the effect of pain and dysfunction among patients with end-stage ankle arthritis, even when removing items 7 and 8, supporting its prior use in numerous clinical studies. Level of Evidence: Level II, prospective comparative study.

Quality of Life in Patients with Gluten Neuropathy; Case-Controlled Study

Background: Gluten neuropathy (GN) is defined as an otherwise idiopathic peripheral neuropathy in the presence of serological evidence of gluten sensitivity (positive antigliadin and/or transglutaminase or endomysium antibodies). We aimed to compare the quality of life (QoL) of GN patients with control subjects and to investigate the effect of a gluten free diet (GFD) on the QoL. Methods: All consecutive patients with GN attending a specialist neuropathy clinic were invited to participate. Overall Neuropathy Limitations Scale (ONLS) was used to assess the severity of neuropathy. The SF-36 questionnaire was used to measure participants&rsquo; QoL. A strict GFD was defined as effectively been able to eliminate all circulating gluten sensitivity-related antibodies whilst on the diet. Results: Fifty-three patients with GN and 53 age and gender matched controls were recruited. Compared to controls, GN showed significantly worse scores in physical functioning, role limitations due to physical health, energy/fatigue and general health subdomains of SF-36. After having adjusted for age, gender and disease severity, being on a strict GFD correlated with better SF-36 scores on the pain domain of the SF-36 (beta 0.317, p=0.019) and the overall health change domain of the SF-36 (beta 0.306, p=0.017). Conclusion: In GN physical dysfunctioning is the major determinant of poor QoL compared to controls. Routine checking for elimination of gluten sensitivity-related antibodies that results from a strict GFD should be encouraged as such elimination ameliorates the overall pain and health scores, indicating better QoL.

Female Sexual Function in Women with Suspected Deep Infiltrating Endometriosis

Objective To evaluate the quality of the sexual function of women with suspected deep infiltrating endometriosis. Methods A cross-sectional, observational and prospective study was conducted between May 2015 and August 2016, in which 67 patients with deep infiltrating endometriosis, suspected or diagnosed, were assessed for epidemiological and clinical characteristics, such as pain level through a visual analog scale (VAS), features of deep infiltrating endometriosis lesions and score on the Female Sexual Function Index (FSFI) before the onset of treatment. The statistical analysis was performed using the software STATA version 12.0 (StataCorp LLC, College Station, TX, USA) to compare the variables through multiple regression analysis. Results The average age of the patients was 39.2 years old; most patients were symptomatic (92.5%); and the predominant location of the deep infiltrating lesions was on the rectosigmoid colon (50%), closely followed by the retrocervical region (48.3%). The median overall score on the FSFI was 23.4; in 67.2% of the cases the score was ≤ 26.5 (cutoff point for sexual dysfunction). Deep dyspareunia (p = 0.000, confidence interval [CI]: 0.64–0.83) and rectosigmoid endometriosis lesions (p = 0.008, CI: 0.72–0.95) showed significant correlation with lower FSFI scores, adjusted by bladder lesion, patients' age and size of lesions. Deep dyspareunia (p = 0.003, CI: 0.49–0.86) also exhibited significant correlation with FSFI pain domain, adjusted by cyclic bowel pain, vaginal lesion and use of gonadotropin-releasing hormone (GnRH) analog. These results reflect the influence of deep dyspareunia on the sexual dysfunction of the analyzed population. Conclusion Most patients exhibited sexual dysfunction, and deep dyspareunia was the pelvic painful symptom that showed correlation with sexual dysfunction.