Cost-utility analysis of certolizumab pegol versus alternative tumour necrosis factor inhibitors available for the treatment of moderate-to-severe active rheumatoid arthritis in Spain.

BACKGROUND: Certolizumab pegol, a PEGylated tumour necrosis factor (TNF)-inhibitor, improves the clinical signs and symptoms of rheumatoid arthritis (RA) when used in combination with methotrexate or as monotherapy. This study evaluatedthe cost-utility of certolizumab pegol versusTNF-inhibitors plus methotrexate in the treatment of moderate-to-severe RA in Spain. METHODS: A Markov cohort health state transition model was developed to evaluate the cost-utility (costs and quality-adjusted life years [QALYs]) of certolizumab pegol versus other TNF-inhibitors licensed in Spain in 2009. Efficacy was measured using the American College of Rheumatology (ACR) responses at 6 months, based on adjusted indirect comparisons from published clinical trials. Utilities were derived from EQ-5D data from certolizumab pegol RA clinical trials. Clinical history and resource use data came from published literature. Unit costs were taken from Spanish databases or published data (cost year 2009). Base case analyses were conducted from the payer perspective, with a lifetime horizon, 3.5 % annual discounting rates for costs and outcomes, and 3 % inflation rate for 2009 onwards. One-way sensitivity analyses were conducted. RESULTS: The average lifetime costs for certolizumab pegol, etanercept, adalimumab (every 2 weeks and weekly) and infliximab (3 mg/kg and 5 mg/kg) in combination with methotrexate were €140,971, €141,197, €139,148, €164,741, €136,961 and €152,561, respectively. The QALYs gained were 6.578, 6.462, 6.430 (for both adalimumab doses), 6.430, and 6.318 (for both infliximab doses), respectively. At a €30,000/QALY willingness-to-pay threshold, certolizumab pegol plus methotrexate dominated adalimumab weekly, etanercept, and infliximab 5 mg/kg, and was cost-effective versus adalimumab every 2 weeks and infliximab 3 mg/kg (all with methotrexate), with estimated ICERs of €12,346/QALY and €15,414/QALY, respectively. Certolizumab pegol monotherapy was more cost-effective versus adalimumab, and less expensive with similar health gains versus etanercept (6.416 QALYs vs 6.492). Univariate analysis showed ICERs to be sensitive to changes in time horizon, ACR response time point, baseline Heath Assessment Questionnaire (HAQ) score, and rate of HAQ-disability index deterioration after discontinuing treatment. CONCLUSIONS: This analysis shows that certolizumab pegol is cost-effective compared with other TNF-inhibitors recommended in Spain for the treatment of RA.

Clinical, Patient-Reported, and Ultrasound Outcomes from an Open-Label, 12-week Observational Study of Certolizumab Pegol in Spanish Patients with Rheumatoid Arthritis with or without Prior Anti-TNF Exposure.

OBJECTIVES: To assess the effectiveness and safety of certolizumab pegol (CZP) in Spanish patients with RA. MATERIALS AND METHODS: SONAR (NCT01526434), a 12-week, open-label, prospective, observational, multicenter study. Patients with active RA for ≥3 months, according to ACR criteria, were treated with CZP (400mg at Weeks 0, 2 and 4, then 200mg every 2 weeks). The primary effectiveness endpoint was change from baseline (CFB) in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12. Other assessments included DAS28(ESR), patient's assessment of arthritis pain (PtAAP-VAS) and Short Form 36-item Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS). Joint inflammation was investigated using Power Doppler (PD) ultrasound (US), to detect effusion, synovial hypertrophy and synovial PD signal. PDUS outcomes assessed CFB to Week 12 in synovial hypertrophy, effusion and PD signal indices. RESULTS: A total of 77/80 enrolled patients received ≥1 dose of CZP. The 12-week mean reduction from baseline (SD) was -0.6 (0.6) for HAQ-DI and -2.2 (1.5) for DAS28(ESR). PtAAP-VAS was reduced from baseline (mean [SD]: -36.8 [26.8]) and improvements in SF-36 PCS and SF-36 MCS were reported. Synovial hypertrophy, effusion and PD signal indices were reduced from baseline to Week 12. One death was reported during the study. CONCLUSIONS: Spanish patients with RA demonstrated improvements in clinical, PDUS and patient-reported outcomes over 12 weeks of CZP treatment. No new safety signals were identified, and the safety profile was in line with previous CZP studies. These results support previous clinical trial findings investigating CZP treatment for active RA.

Laparoscopic approach to esophageal perforation secondary to pneumatic dilation for achalasia.

BACKGROUND: Perforation of the esophagus after pneumatic dilation for achalasia is a severe complication which should be treated accurately in order to obtain a successful immediate outcome and a satisfactory result for the underlying condition. METHODS: Five consecutive patients presenting with distal esophageal perforation after pneumatic dilation for achalasia were included in this study. All patients had gastrografin swallow performed to confirm the perforation, and one patient was also submitted to flexible esophagoscopy. Laparoscopic approach was performed in all patients with five portals. The phrenoesophageal membrane was opened on its anterior aspect. The distal esophagus was dissected free, and perforations were identified with the help of methylene blue or milk administration through the esophageal tube. All perforations were sutured with interrupted absorbable sutures. Contralateral myotomy and partial anterior Dor fundoplication completed the operation. Endoscopic control of length of myotomy and watertightness of mucosal closure was performed in all cases. RESULTS: There were no intraoperative complications. After surgery all patients were maintained with nil per os until a barium swallow showed no leakage. One patient had a radiologic leakage sustained for 1 week. All patients were dismissed uneventfully. At 6 months after surgery, esophageal manometry was performed. Mean lower esophageal sphincter resting pressure had fallen from 30 to 8.7 mmHg. CONCLUSIONS: Laparoscopy offers an excellent approach to treat distal esophageal instrumental perforations, perhaps even better than open surgery. Suture of the perforation, contralateral myotomy and partial anterior fundoplication is a good option in the treatment of perforated achalasia after pneumatic dilation.

Clinical, Ultrasound, and Predictability Outcomes Following Certolizumab Pegol Treatment (with Methotrexate) in Patients with Moderate-to-Severe Rheumatoid Arthritis: 52-Week Results from the CZP-SPEED Study.

INTRODUCTION: To assess the impact of certolizumab pegol (CZP) treatment on clinical, patient-reported, and musculoskeletal ultrasound outcomes and to determine the treatment response time point most predictive of long-term outcomes in Italian patients with rheumatoid arthritis (RA). METHODS: CZP-SPEED (NCT01443364) was a 52-week, open-label, prospective, interventional, multicenter study. Biologic-naïve patients with moderate-to-severe active RA, who had failed at least one DMARD treatment, received CZP (400 mg at weeks 0, 2, and 4, then 200 mg every 2 weeks) concomitantly with methotrexate. The primary objective was to identify the time point of clinical response {decrease in 28-joint Disease Activity Score [DAS28(ESR)] ≥ 1.2} most predictive of a clinical response at week 52. Additional clinical and patient-reported outcomes were measured. Power Doppler (PD) ultrasound was used to assess synovial effusion, synovial proliferation, PD signal, cartilage damage, and bone erosion according to international guidelines. RESULTS: A total of 132 patients were enrolled and received CZP; 91/132 (69%) completed to week 52. Predicted 52-week responses for early responders (week 2 onwards) were between 65% and 70%. Rapid improvements in joint cavity widening and PD signal were observed to week 8 and maintained to week 52. Cartilage damage and bone erosion were stable over 52 weeks. No new safety signals were identified. CONCLUSION: In Italian CZP-treated patients with moderate-to-severe RA, week 12 clinical responses may be predictive of long-term response at week 52. Rapid improvements in clinical, patient-reported, and musculoskeletal ultrasound outcomes were maintained to week 52. These data may aid rheumatologists to make earlier treatment decisions. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01443364. FUNDING: UCB Pharma.

Gastric tube volume after duodenal switch and its correlation to short-term weight loss.

BACKGROUND: Bariatric operations may have a restrictive and a malabsorptive component. The restrictive component is considered key for short-term weight loss. However, there are important volume discrepancies between gastric reservoirs in different bariatric surgical techniques, which questions the real meaning of the restrictive part of the operation. We have investigated the relationship between residual gastric volume after sleeve gastrectomy in duodenal switch (DS) and weight loss over the first postoperative year. METHODS: 14 patients submitted to a modified DS and one patient submitted to a sleeve gastrectomy were studied. All patients had an abdominal CT performed between the third and the ninth postoperative month to measure residual gastric volume. Gastric tube volume was correlated to early postoperative weight loss. RESULTS: Mean excess BMI loss was 75% at 12 months. Mean gastric tube volume was 208 cc. Gastric volume was not related to preoperative weight or BMI; instead, it was directly related to patient's height. There was no statistical relation between gastric volume and weight loss at 3, 6, 9 or 12 months after the operation. CONCLUSION: After DS, gastric tube volume is not directly related to weight changes. Other factors could have influence on intake restriction, such as gastric tube compliance or different mechanisms of satiety induction, because no differences in weight loss were observed between narrow tubes and wider ones, despite important variations in volume.

Proximal duodenal-ileal end-to-side bypass with sleeve gastrectomy: proposed technique.

Proximal duodenal-ileal end-to-side bypass with sleeve gastrectomy is a new bariatric technique based on the biliopancreatic diversion with duodenal switch in which after the sleeve gastrectomy, the duodenum is anastomosed to the ileum in a Billroth-II fashion. A 200-cm common channel-alimentary limb is devised. Anticipating an appropriate weight loss, at least similar to that obtained after gastric bypass, theoretical benefits for operated patients are a shorter operative time, the performance of only one anastomosis, and no mesentery opening. A prospective trial is now being conducted to find out the results of the procedure and to compare them to those obtained with gastric bypass and standard duodenal switch.

Mucocele of the gastric tube after conversion of vertical banded gastroplasty to duodenal switch: not just a radiological image.

We present two patients who underwent a duodenal switch operation after a failed vertical banded gastroplasty. Both patients had a complicated postoperative course because of an abdominal infection, and both presented the radiological image of a gastric fundus mucocele in the part of the fundus excluded between two staple-lines. Although initially considered as a radiological image with no clinical significance, the presentation of the second case with the same abdominal complication led us to contemplate the possibility of a connection between the gastric mucocele and the postoperative infection.

Technique of Hill's Gastropexy Combined with Sleeve Gastrectomy for Patients with Morbid Obesity and Gastroesophageal Reflux Disease or Hiatal Hernia.

BACKGROUND: Observational studies based on quality-of-life and endoscopy relate sleeve gastrectomy (SG) to gastroesophageal reflux disease (GERD), while some functional studies have demonstrated a decrease in esophageal exposure to gastric acid after SG. Currently, it is recommended to treat hiatal hernia along with the SG. However, as the sleeve gastrectomy involves the resection of the fundus, it is not possible to add a traditional fundoplication to the closure of the hiatus. METHODS: Based on the classic works of Hill et al., and more recent studies by Swänstrom and Aye, our group has incorporated a modified Hill's gastropexy to the sleeve gastrectomy for patients with pathologic GERD and/or huge hiatal hernia submitted to weight loss surgery. RESULTS: A 28-year-old male patient, 43 kg/m(2) BMI, with a small hiatal hernia and pathologic GERD was scheduled for sleeve gastrectomy. After complete fundus and left crus dissection, the phrenoesophageal membrane was opened and the distal esophagus dissected. The hiatus was closed with interrupted sutures. The sleeve was completed over a 42-French bougie. The preaortic fascia was dissected at the root of the crura and three interrupted sutures placed approximating the gastroesophageal junction to the aforementioned fascia. At 6 months from the operation, weight loss has been satisfactory and the patient does not complaint GERD. Barium swallow demonstrates absence of gastroesophageal reflux, pHmetry and manometry have normalized, and endoscopy shows no esophagitis. CONCLUSIONS: Gastropexy to the preaortic fascia is a possible antireflux technique to combine with SG.

"Right-angled" stapled latero-lateral duodenojejunal anastomosis in the duodenal switch.

A simplified technique to perform the duodeno-enteral anastomosis in the duodenal switch is presented. A linear stapled duodeno-jejunal side-to-side anastomosis is performed. The technique is easy and rapid to perform, avoids passing an anvil through the mouth of the patient and is safe for the patient, with satisfactory short-term results.

Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S). One to three-year follow-up.

Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a new operation for morbid obesity based on the biliopancreatic diversion in which a sleeve gastrectomy is followed by an end-to-side duodeno-ileal diversion. The preservation of the pylorus makes possible the reconstruction in one loop, which reduces operating time and needs no mesentery opening. We review the results obtained on the first 50 operated patients with 1 to 3 years follow-up. Eighteen men and 32 women with a mean BMI of 44 kg/m(2) were operated on. Hypertension was present in 50%, sleep apnea in 30%, hypertriglyceridemia in 60% and hypercholesterolemia in 43%.There were 27 type two diabetics, most of them on insulin therapy. There were two gastric staple-line leaks and one long-term subphrenic abscess. Follow-up is complete for 98% of the patients. Excess weight loss reached 94.7% at 1 year, and it was maintained over the second and third year. At 1 year, mild anemia has been detected in 10% of the cases. Albumin concentration was under normal levels in 8% of the patients in the first postoperative year, but all patients recovered to normal levels by the third postoperative year. All diabetic patients have normalized glucose or HbA1c levels after the sixth postoperative month with no need of anti-diabetic therapy. SADI-S is a promising operation which offers excellent weight loss and metabolic results. The elimination of one anastomosis reduces operative time and decreases the possibility of surgically related complications.