V. Coret

Eficiencia de diferentes dosis de rituximab en la artritis reumatoide

OBJECTIVE Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. MATERIAL AND METHODS Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1g infusions separated by 15 days; (G2) First course 2 infusions of 1g followed by 2 infusions of 500mg; (G3) First course and followed by 2 infusions of 500mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analysed by groups. RESULTS Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8 to 70.7] months vs 33.5 [22.7 to 44.3]; P<.001) and a lower rate of severe adverse events with only a slight increase in the rate of retreatment (courses/patient-year [95% CI] 1.66 [1.39 to 1.93] vs. 1.01 [0.69 to 1.34]; P=.005), and in the costs (median/patient-month, €484.89 vs. €473.45). Although group 3 was €41.20/patient-month cheaper than group 2, it was associated with a higher rate of re-treatments and shorter retention of rituximab (P<.001). CONCLUSIONS The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option.

AB1078-HPR Telephone Follow-Up, Standardized To The Initiation of Biologic Therapy of Patients with Rheumatoid Arthritis (RA) in A Specific Unit of Biologic Therapy. Pilot Study

Objectives To know the usefulness of follow-up call legalized at the beginning of biologic therapy and patient contact with consultation of nursing after the start of treatment. Methods Observational study cross.Patients: We collected 120 patients who began treatment with biologic therapy, intravenous or subcutaneous from December 2013 to November 2015. Protocol: Protocol is education for self-management of subcutaneous biological therapy at the beginning of the treatment. This Protocol includes a follow-up call from the consultation of nursing that matches the first administration of the treatment at home or within 3–5 days after the first infusion. This call is made in the case of the biological subcutaneous as per guideline: etanercept (7 days), adalimumab (14 days), golimumab (28 days), tocilizumab (7days), certolizumab (14 days), abatacept (7days) either guideline prescribed in case of dose reduction. Offers the possibility of contact (telephone and e-mail) with the consultation of nurses in case of doubt or incidence during treatment and is analytical control to the month of the beginning of nurse telephone consultation. Statistical analysis: a descriptive analysis of the main variables. Results 120 patients with RA initiated treatments were: etanercept 33,3% (n40), adalimumab 8,3% (10), tocilizumab sc 20% (24), abatacept sc 12,5% (15), golimumab 13,3% (16), rituximab 6,7% (8), certolizumab pegol 3,3% (4), biosimilar 2,5% (3). In terms of the associated FAME: none 38,3% (46), methotrexate 49,2% (59), Leflunomide 8.3% (10), sulfasalazine 1,7% (2), hydroxychloroquine 2,5% (3).They were detected in the Protocol call patients with incidences 14,16% (17): local reaction3.3% (4), pruritus 5.8% (7), upset general 0.8% (1), diarrhea 0.8% (1), constipation 0.8% (1), headache 1.7% (2). The patients called the nursing consultation to communicate incidences 10.83% (13): anemia 0.8% (1), hypertransaminasemia 1,7% (2), implant dental 0.8% (1), bruising 0,8% (1), inefficiency 6.7% (8). Also communicated to the consultation of nursing infections during 16.6% (20): urinary tract infection 5,8% (7), upper respiratory tract infection 1,7% (2), upper respiratory tract infection+herpes simplex 0,8% (1), lower respiratory tract infection 3,3% (4), surgical wound infection 0.8% (1), dental infection 0,8% (1), herpes simplex 0,8% (1), gastroenteritis 0,8% (1), not frightening infection 1,7% (2).Patients who started biologic therapy in the period studied only 8.3% (10) changed treatment.The emergence of new comorbidities were detected during treatment with biologic therapy 4,16% (5): hypertension 0,8% (1), hypertension + diabetes mellitus II 1,7% (2), nonspecific Interstitial pneumonia 0,8% (1), psoriasis 0,8% (1). Conclusions The follow-up call is a useful tool for the control of security of the new beginnings of biological agents. It could foster adherence to treatment monitoring at home and offering the possibility to communicate with the nursing. Disclosure of Interest None declared

AB1109 Dose de-escalation in a specialized outpatient clinic on biological therapy: cost minimization observational study

Objectives To estimate the annual cost in the use of biological therapy (BT) in patients with different rheumatic diseases when dose modifications are undertaken in daily clinical practice in a specialized outpatient clinic during 2016 and to compare the results with data obtained in 2013. Methods Design: Cost minimization observational study under conditions of clinical practice. Patients: Patients with different rheumatic diseases who come to a specialized outpatient clinic on BT in the Rheumatologic department at a tertiary Spanish hospital (with a tight follow-up) that had been treated with BT under reduced doses during 2016 were collected. Protocol: Reductions in treatment dose or dose frequency were established empirically and were carried out by their rheumatologist in those patients who were in remission (DAS 28 <2,6) for at least 6 months without steroids. Main outcome: Reduction of annual average cost in euros in BT used in patients who are in dose reduction in clinical practice in 2016. Secondary outcome:Differences in annual costs reduction in 2016 compared with 2013. The cost reduction was calculated by comparing the actual expenditure (after modifying treatment dose in clinical practice) with the theoretical costs (official price) in case you had not made the adjustment. Statistical analysis: Sample descriptive analysis. Reducing annual absolute costs and by treatment after tapering down doses in clinical practice in 2016 and the differences found between 2013 were calculated. Results During 2016, the dose of the BT of 168 patients (94 Subcutaneous BT and 74 intravenous BT) were modified in clinical practice after reaching clinical remission:mean of DAS 28 (mean±SD)=2.31±0.76 or BASDAI (mean±SD)=2.15±1.39 without radiographic progression. Most patients were women (n=113;67%)and had rheumatoid arthritis (n=103;62%) and the rest were distributed among: spondyloarthritis (n=28;17%), psoriatic arthritis (n=22;13%), juvenile idiopathic arthritis (n=10;5%) and Systemic Lupus Erithematosus (n=5;3%). No patients treated with certolizumab or anakinra was modified treatment doses. During this period, 5 patients discontinued BT (3 remissions and 2 minor adverse events). Table 1 shows the number of patients by type of BT and costs. The BT dose reduction in clinical practice during 2016 represented a saving of 676,501.67€ and a greater efficiency of treatments while in 2013, only 86 patients (30 etanercept, 15 adalimumab, 16 Infliximab (Remicade), 15 Tocilizumab IV and 55 Rituximab) had a modified dose of BT in clinical practice assuming a saving of 396,995.46€. The difference in the annual cost reductions in 2016 compared to 2013 meant a saving of 279.506,21€ more in the last year. Table 1. Conclusions In rheumatic diseases we may do a dose de-escalation of BT in patients who go into remission and therefore we could reduce the associated costs of BT and being more efficient with the treatments. We believe that it is important to create specialized outpatient clinics on BT where a tight-control management of these patients and an individualized treatment are carried out. Disclosure of Interest None declared

SAT0201 Treatment Adherence in Rheumatoid Arthritis (RA) Patients Followed in a Specific Biological Therapy Unit. a Pilot Study: Table 1.

Objectives To study the adherence to biologic therapy (BT) of patients with RA. Methods Design: Cross-sectional study. Patients: 40 RA-pts treated with BT (50% wit subcutaneously [sc] and 50% with intravenously [iv]) with or without synthetic DMARDs were consecutively recruited from a specific unit of BT. Protocol: Patients with sc BT are alternately reviewed every three months in general and specific (only BT pts) outpatient clinic. Iv BT patients are checked each time the drug is infused. At 5 days from 1st iv BT infusion or in the day that 2nd dose of sc BT is given, patients receive a call from the nurse to confirm that everything went well. Patients with sc BT have a self-injections diary and direct free telephone access to the nurse. Variables: Demographic, clinical and laboratory, therapeutic, Morisky-Green adherence questionnaire (MGAQ), control of the number of sc BT doses withdrawn from outpatient hospital pharmacy, assisting to infusions in the case of iv BT and removal of synthetic DMARDs in the drugstores using “XXI electronic prescription” (a software used to control the dispensations in the public health system in Andalusia) in the last 6 months. Outcome variables: (1) level of adherence and (2) compliance level with MGAQ. MGAQ considers that the patients are adherents when they give 3 or more responses indicative of adherence. Good drug withdrawal from hospital pharmacy or drugstore was defined as removal of >80% of the prescribed dose. Adherence to BT and synthetic DMARDs was measured independently. The degree of adhesion was classified as good (3 or 4 correct responses in MGAQ and good drug withdrawal), medium (3 or 4 good responses in MGAQ but bad drug withdrawal or vice versa) and bad (<3 good responses in MGAQ and bud drug withdrawal). Statistical analysis: Descriptive analysis of the main variables. Adherence between sc BT and iv BT was compared using T-Student. Results The main characteristics of the patients (n=40) are shown in the table. 10/40 patients were in monotherapy. 37/40 (92.5%) showed good adherence to BT, 3/40 (7.5%) moderate and bad none. There was no difference in the level of adherence to BT among sc BT and iv. BT (90% vs. 95% good adhesion; p=0.50) nor between BT alone or in combination with DMARDs (70% vs. 100% good adhesion; p=0.12). The level of adherence was good with BT in 100% of the patients and in the 70% with synthetic DMARDs.Table 1. Demographic-clinical features Variables Patients Age (years), mean (DE) 57,1 (9,3) Sex (Female), n (%) 32 (80) Race (Caucasian), n (%) 38 (95) Rheumatoid factor, n (%) 35 (87,5) Anti–cyclic citrullinated peptide, n (%) 33 (82,5) Erosions, n (%) 32 (80) DAS28 at protocol, mean (DE) 2,9 (0,9) HAQ at protocol, mean (DE) 1,1 (0,6) Delay to diagnosis (months), mean (DE) 21,9 (2,34) Disease duration (months), mean (DE) 138,8 (6,4) Conclusions Adherence to BT in RA-patients in a specific unit of BT that controls the treatment adherence is very good with the BT and good with synthetic DMARDs. Patients treated with sc or iv. BT and those with monotherapy or combination therapy are equally adherents. These data represent are only a preliminary study. Disclosure of Interest None declared

FRI0177 Analysis of Effectiveness, Safety and Cost of Different Doses of Rituximab in a Cohort of Patients with Rheumatoid Arthritis

Objectives To evaluate the effectiveness, cost and safety of Rituximab (RTX) in patients with rheumatoid arthritis (RA) depending on the dose used. Methods Design: Observational, retrospective study. Patients: Patients with RA treated with at least one dose of RTX and followed in the department of Rheumatology, Hospital de Malaga, were included. According to the doses used, 3 groups were obtained: (1): First and following courses consisting of 2 infusions of 1g, 15 days apart; (2): First course of 2 infusions of 1g followed by courses of 2 infusions of 500mg, 15 days apart; and (3): First course and following courses consistent on 2 infusions of 500mg, 15 days apart. Courses were repeated “on demand”, according to clinical presentation. Outcome variables: Primary: Effectiveness of treatment between groups. Secondary: cost and incidence rate of adverse effects (AE).Protocol and description of variables: RA patients who had received at least one infusion with RTX from 2007-2012 were included. The number of courses adjusted to treatment time (patient-years) were analyzed, the direct costs were defined as the cost of treatment with RTX per group and were compared with the theoretical costs of systematic semiannual courses. AE rates by type and severity stratified by treatment group. Statistical analysis: the primary endpoint of effectiveness, duration of treatment with RTX, was analyzed using Kaplan Meier and the comparation between groups was made with the Log Rank. Incidence rates of AE was performed. Results 52 patients were included. The groups showed only differences in sex ratio and order of RTX was used compared to other biologic therapies. The cohort was followed for 135.34 patient-years. Group 2 was the one with longer time in treatment with RTX. Group 1 required less adjusted to time courses. Group 2 was the most expensive with a median cost per patient of € 484.89 per month. The savings per patient per year in group 3 compared with group 2 was 556.48€ and in group 1 compared to group 2 was 137.28€. The biggest saving occurred with the administration of courses “on demand” respect “systematic” (479.32€ versus 799.74€). No differences were found in the incidence of total AE (group 1 =33%, group 2 =35%, group 3 =33%). When only considered severe, the incidence rate (IR) was higher in group 1 (11%) compared to the other 2 (group 2 =3% and group 3 =0%; p=0, 05). The IR of serious infections was higher in group 1. Conclusions The administration of a full dose course followed by reduced dose courses seems slightly more expensive but the most effective option. Patients treated from the start with full dose courses, needed fewer courses/patient-year. Dose reducted courses from full dose courses do not produce huge savings compared to money spare achieved by the administration “on demand”. The rate of AE may be greater in patients treated with full doses of RTX compared with those treated with low doses, although these differences might be biased, in part, by the greater proportion of first line biologic treated patients of group 1. The IR of serious infections was similar to the expected in a first biological treatment option. Disclosure of Interest None declared

SAT0089 Cost Minimization Observational Study after Dose Optimization in A Specialized Outpatient Clinic on Subcutaneous Biological Therapy

Objectives To estimate annual cost in the use of subcutaneous BT (scBT) in patients with rheumatic diseases when dose modifications are undertaken in daily practice in a specialized outpatient clinic of a tertiary hospital during 2013 and to compare the results with data obtained in 2012. Methods Cost minimization, cross-sectional observational study.Patients with different rheumatic diseases who are following a tight control care in a specialized scBT outpatient clinic of a tertiary Spanish hospital who have been treated with BT under conventional and modified doses during 2013 were collected.Reductions in treatment dose were made at the discretion of their physician in patients who were in remission for at least 6 months.Main outcome:Reduction of annual average cost in euros in scBT used in clinical practice in 2013. Secondary variables:demographics, type of rheumatic disease, clinical and laboratory data. The cost reduction was calculated by comparing the real expenditure (after modifying treatment dose) with the theoretical costs if he had not made the adjustment. Statistical analysis:Descriptive analysis was performed. Reducing annual absolute costs and by treatment after the adequacy of dose in 2013 and the differences found between 2012-2013 were calculated. Results A total of 204 patients were followed in the monographic scBT clinic in 2013, with 333 visits [1.58 visits/patient (min.1-max.5)]. Most patients had RA (n=123, 60.3%) and the rest were distributed among: spondyloarthritis (n=37, 17.6%), psoriatic arthritis (n=33; 16.2%), juvenile idiopathic arthritis (n=11; 5.4%) and one SAPHO (0.5%) treatments received in the outpatient clinic were:etanercept, adalimumab, golimumab, abatacept, certolizumab and anakinra. During 2013, the dose of the scBT of 43 (21.1%) patients (19 RA,6 SpA,16 PsA,2 JIA) were modified in clinical practice because they reached clinical remission:DAS28[(mean (±SD)]=2.57 (0.85) or BASDAI [(mean (±SD)]=2.67 (1.59), without radiographic progression. No patients treated with golimumab, abatacept, certolizumab or anakinra was modified treatment doses. Among the 43 patients, 28 patients were treated with Etanercept and 15 with Adalimumab. The BT dose reduction in clinical practice during 2013 represented a saving of €205,947.68 and a greater efficiency of treatments while in 2012, only 28 patients (18 etanercept and 10 adalimumab) had a modified dose of scBT in clinical practice assuming a saving of €124,120.79. Conclusions In rheumatic diseases we may adjust the dose of treatment in patients who go into remission reducing the associated costs of scBT and being more efficient with the treatments. A largest number of patients in dose reduction, during 2013, could be attributed to a tight-control management carried out since the creation of a specialized BT outpatient clinic. We believe it is important to create outpatient clinics specialized in BT where periodic assessments with close monitoring of these patients and an individualized treatment are carried out. Disclosure of Interest S. Manrique-Arija Grant/research support: Pfizer, C. Romero-Barco: None declared, M. Ordoñez-Cañizares: None declared, I. Ureña: None declared, L. Cano: None declared, F. Jimenez-Nuñez: None declared, L. Nieves-Martin: None declared, N. Mena-Vazquez: None declared, M. Irigoyen: None declared, A. Ponce: None declared, V. Coret: None declared, M. Belmonte-Lopez: None declared, M. Rodriguez: None declared, A. Fernandez-Nebro Grant/research support: Pfizer, Roche, Speakers bureau: Pfizer, Roche, Abbvie, MSD, BMS DOI 10.1136/annrheumdis-2014-eular.4525

AB0583 Effectiveness and safety of short-term treatment of active rheumatoid arthritis (RA) moderate to severe with tocilizumab

Objectives To evaluate the effectiveness and safety of tocilizumab (TCZ) for the treatment of active RA in our department. Methods Type of study: Prospective cohort. Inclusion criteria: RA-patients (new ACR-EULAR criteria) who have failed to at least one anti-TNF drug. Variables and Statistic: We evaluated the monthly changes of DAS28 and HAQ during the first year of treatment with TCZ using repeated measures ANOVA and survival of TCZ over the first 2 years with survival curves of Kaplan-Meier. Safety was assessed collecting adverse events, withdrawals due to safety and deaths. Results We included 35 patients, 19 of them from clinical trials (88.6% women with a mean age of 55.3±11.1 years) with a total follow-up for 29.7 person-years, a median duration of disease of 10.0±7.3 years. Anti-CCP was positive in 22 patients (64%) and the rheumatoid factor in 31 (89%). Thirty-one (89%) had radiographic erosions and 1 patient had previous orthopedic surgery (arthroplasty of both knees). The number of previous DMARDs: 6 (17%) had received one, 11 (31%) two, 11 (31%) three, 1 (3%) four, 2 (5.7%) five, and one (3%) six DMARDs. The mean of DMARDs was 2.4±1.3 per patient. Twenty (60%) patients had taken MTX (mean dose 16.4±4.8 mg/week), 6 (17%) had received LF (mean dose 20mg/24 h) and 1 (3%) hydroxychloroquine (mean dose of 400mg/24 h). The number of previous biological therapies used was: 8 (22.9%) patients had received one, 13 (37%) two, 7 (20%) three and 6 (17%) four, which represented an average of 2, 3±1.0 per patient biologics. The DAS28 improved progressively during the first year with TCZ (F =17.8; Trace Pilai p=0.008). Although the most significant change occurred in the first month (mean difference 1.9 (95% CI =0.4 to 3.3, p=0.002, Bonferroni adjustment p=0.010) after 1 year reached an estimated mean difference of 3.1 (95% CI =1.3 to 4.8, Bonferroni adjustment p=0.002).The HAQ also improved progressively with TCZ the first 3 months (F =3.5; Trace Pilai p=0.043), but in a much slower than the DAS28 [mean difference from baseline to third month in 0.436 (95% CI = - 0056 to -0929; Bonferroni adjustment p=0.103). Twenty (57.1%) patients continued with treatment after a median of 18 months (CI 95% 11.7 to 24.2 months) which resulted in the suspension rates of 14%, 17% and 26% at 3, 6 and 12 months, respectively. The causes of withdrawal or abandonment of treatment with TCZ were: 2 (6%), infections (severe cellulitis, and conjunctivitis), 2 (6%) due to failure of efficacy, 3 (9%) for infusional reaction, 1 (3%) by asymptomatic neutropenia, 3 (9%) patient’s decision, 2 (6%) due to gastrointestinal intolerance and 1 (3%) for protocol violation. Of all dropouts, only 8 patients were withdrawn due to adverse effects (including the only serious case was a right lower limb cellulitis). Conclusions In patients with RA who have previously failed other biologic therapies, TCZ produced a rapid improvement of inflammatory activity and physical function. The rate of discontinuation due to adverse events was relatively low for this subgroup of patients (23%), and serious adverse events were unusuals. Disclosure of Interest None Declared

AB0731 Risk factors and prevalence of osteoporosis in patients with systemic lupus erythematosus

Objectives To determine the prevalence and risk factors of osteoporosis in patients with Systemic Lupus Erythematosus (SLE) in our hospital. Methods Design: Retrospective study. 101 SLE-patients were studied in the Rheumatology Department in Carlos Haya Hospital in Malaga. Patients’ disease and demographic data (including SLEDAI) were collected. Bone mineral density (BMD) was measured at the lumbar spine (LS) and femoral neck (FN) with a DEXA-LUNAR- PRODIGY. The results were classified according to WHO criteria. Thoracic and lumbar spine radiographies were assessed using the Genant method. Results Data from 98 SLE-patients were available for analysis (94% women, mean age 42±14 years). Only 61 patients (62%) had a DEXA. Patients with DEXA were similar to others in terms of gender, race, history of fracture, alcohol, tobacco, sedentary, photosensitivity or use of corticosteroids. However, patients with DEXA were older (42.3±14 years vs. 40.6±13.5 years, T-test p=0.002), had a longer duration of lupus (120.7±103.3 months vs. 89.6±68.4, U of MW p no significant differences were found in the prolonged steroids taking (>6 months) [4 (44.4%) vs. 30 (66.7%), Fisher’s exact test p=0.266] and SLICC (0.9±0.9 VS. 0.9±1.5, T-test p=0.937). Conclusions The prevalence of osteopenia and osteoporosis in our SLE-patients is greater than in general population and it is more frequent in older age, menopausal status and history of fracture. The profile of patients with DEXA reflects that this test is not request systematically in clinical practice but only to those patients with more osteoporosis risk, this is a considerable bias in our study. The small sample size and the systematic use of prophylactic treatmentin patients treated with corticosteroids may be also explained why it was not found relationship between glucocorticoids and low mineral bone density Disclosure of Interest None Declared

AB1247 Application of a triage approach reduces the requirement for central DXA

Objectives To analyse if using risk indices and PIXI scans jointly would reduce requirement for central DEXA to diagnose postmenopausal OP. Methods A stratified sample of postmenopausal women was selected: a random sample of 305 postmenopausal women from Primary care, and 200 consecutive postmenopausal women referred for central DXA measurement from tertiary care. Inclusion criteria: Caucasian female, age ≥50 yrs, and full menopause (amenorrhea ≥12 mo.). Exclusion criteria: previous diagnose of OP, previous treatment with OP drugs (calcium and/or vitamin D and/or estrogens for menopausal symptoms treatment were allowed) or steroids and other drugs related with low BMD, and institutionalized persons OR Steinbrocker’s functional grade 4. Informed consent was obtained. Four risk indices were calculated: SCORE, ORAI, OSIRIS, and OST. All participants underwent two different BMD measurements: a non-dominant heel BMD (PIXI Lunar, Software #50699, GE Corp.), and a central DXA of the hip and lumbar spine (Lunar Prodigy Advance, Software ENCORE 2006, PA+300274, GE Corporation). OP definition according to the WHO was used. Statistical analyses: The diagnostic utility was measured by ROC curves. We calculated the sensitivity and specificity for risk indices, PIXI, and all possible combinations. Logistic regression was performed to build a risk model with the presence or absence of osteoporosis at the central DEXA as dependent variable. The thresholds was established in 2 ways: 1) a cutoff point where the sensitivity and specificity are maximized, and 2) with two cutoff points, where both it sensitivity and specificity reached 90%. Results 505 Caucasian women with a mean (SD) 61 (8) yrs, were recruited. Median (p25-p75) scores for each risk index were: OST 1 (0-3), ORAI 10 (7-14), and SCORE 8 (6-11). The mean (SD) PIXI T-score of the calcaneus was -0.33 (1.14). The mean (SD) femoral neck T-score was -1.01 (1.05), total femur was -0.59 (1.19) and lumbar T-score was -1.18 (1.36). The prevalence of osteoporosis by central DXA was 20% (n=102), 19% (57) in primary care and 23% (45) in tertiary care. The combined algorithm PIXI + OST + SCORE was the greatest area under the curve obtained: 75% (95% CI, 71 to 79). Most favorable threshold for this algorithm stratified subjects into high, medium, and low risk according to 2 cutoff (-20 and -5, respectively), and the most favorable subsequent decision was referral for central DXA if the medium or high risk categories were reached. According to this algorithm (table) 11 (2.2%) false negatives were obtained, but 257 (52%) central DEXA were avoided and a 20 – 35% in costs could have been saved. Table 1. Distribution of population by disease status and dichotomous test result (DEXA diagnosis columns and algorithm triage in rows) Osteoporosis – + Prueba  bajo 226 11 237  medio 129 39 168  alto 38 51 89 Total 393 101 494 Conclusions A triage based on a combined algorithm composed of PIXI + OST + SCORE reduces reduce the requirements of central DEXA a 52%, and may savings cost. Disclosure of Interest None Declared