Value of mesenchymal stem cell therapy for patients with septic shock: an early health economic evaluation.

BACKGROUND.: This study estimates the maximum price at which mesenchymal stem cell (MSC) therapy is deemed cost-effective for septic shock patients and identifies parameters that are most important in making treatment decisions. METHODS: We developed a probabilistic Markov model according to the sepsis care trajectory to simulate costs and quality-adjusted life years (QALYs) of septic shock patients receiving either MSC therapy or usual care over their lifetime. We calculated the therapeutic headroom by multiplying the gains attributable to MSCs with willingness-to-pay (WTP) threshold and derived the maximum reimbursable price (MRP) from the expected net monetary benefit and savings attributable to MSCs. We performed scenario analyses to assess the impact of changes to assumptions on the study findings. A value of information analysis is performed to identify parameters with greatest impact on the uncertainty around the cost-effectiveness of MSC therapy. RESULTS: At a WTP threshold of $50,000 per QALY, the therapeutic headroom and MRP of MSC therapy were $20,941 and $16,748, respectively; these estimates increased with the larger WTP values and the greater impact of MSCs on in-hospital mortality and hospital discharge rates. The parameters with greatest information value were MSC's impact on in-hospital mortality and the baseline septic shock in-hospital mortality. CONCLUSION: At a common WTP of $50,000/QALY, MSC therapy is deemed to be economically attractive if its unit cost does not exceed $16,748. This ceiling price can be increased to $101,450 if the therapy significantly reduces both in-hospital mortality and increases hospital discharge rates.

A cost-effective cell- and matrix-based minimally invasive single-stage chondroregenerative technique developed with validated vertical translation methodology.

Introduction The morbidity and significant health economic impact associated with the chondral lesion has led to a large number of strategies for therapeutic neochondrogenesis. The challenge has been to develop techniques that are cost effective single-stage procedures with minimal surgical trauma that have undergone rigorous preclinical scrutiny and robust reproducible assessment of effectiveness. A biological repair requires the generation of a cellular and matrix composite with appropriate signalling for chondrogenic differentiation. Methods and results A technique was developed that allowed chondrogenic primary (uncultured) cells from bone marrow aspirate concentrate, combined with a composite hydrophilic and fibrillar matrix to be applied arthroscopically to a site of a chondral lesion. The construct was tested in vitro and in animal experiments before clinical trials. Clinical trials involved 60 patients in a prospective study. Symptomatic International Cartilage Repair Society grade 3 and 4a lesions were mapped and treated. Pre- and postoperative clinical assessments showed statistically significant improved outcomes; Lysholm Knee Scoring Scale (mean 52.8 to > 76.4; P < 0.05) International Knee Documentation Committee (mean 39 to > 79 P < 0.05) and Knee injury and Osteoarthritis Outcome Score (64.5 to >89.2 P < 0.05). Postoperative magnetic resonance imaging was evaluated morphologically (magnetic resonance observation of cartilage repair tissue, average MOCART score 72) and qualitatively; the regenerate was comparable to native cartilage. Conclusions This technique is effective, affordable, requires no complex tools and delivers a single-stage treatment that is potentially accessible to any centre capable of performing arthroscopic surgery. Good clinical results were found to be sustained at five years of follow-up with a regenerate that appears hyaline like using multiple magnetic resonance measures.

Insurance approval of mesenchymal stem cell for acute GVHD in Japan: need of follow up for some remaining concerns.

Acute graft-versus-host disease (aGVHD) is a major obstacle following allogeneic hematopoietic stem cell transplantation. Steroid is the standard treatment for aGVHD grade II-IV; however, nearly half of patients do not respond to the therapy. Many drugs have been proposed, but no standard therapy has been determined. This is because of the resistance to these drugs and of infections due to prolonged immunosuppressive states. Over the past decade a new approach using mesenchymal stem cells (MSCs) has been emerging in Japan and western countries. MSCs have unique characteristics such as specific immunosuppressive properties, no immunogenicity on their own and supportive activity for hematopoiesis. Most of the published trials have reported a favorable effect in acute GVHD, but a phase III trial failed to reach the primary endpoint, although, subgroup analyses found significant effects on gut and liver GVHD in the patients with MSCs infusion. In Japan several institutes are trying to develop MSC for clinical use in post HSCT patients. However, several limitations make it difficult to use MSC in clinical practice. Recently we conducted a phase II/III study using MSC (JR-031) for patients with steroid-refractory grade III or IV aGVHD. From the feasible clinical results, JR-031 was approved by PMDA as the first product which meets the Act to Revise the Pharmaceutical Affairs Act and the Act to Ensure the Safety of Regenerative Medicine. The cost of one series of the treatment is more than ten million yen. Now we encounter new issues such as cost, indication, safety and efficacy. The mechanism of MSC is still unclear and potential concerns about ectopic tissue formation and MSC related malignancy in vivo remain. In conclusion, MSC infusions are well tolerated and show benefit in some patients without adverse safety effects; however, long-term follow-up is needed to be more certain of this.

The effect of concentrated bone marrow aspirate in operative treatment of fifth metatarsal stress fractures; a double-blind randomized controlled trial.

BACKGROUND: Fifth metatarsal (MT-V) stress fractures often exhibit delayed union and are high-risk fractures for non-union. Surgical treatment, currently considered as the gold standard, does not give optimal results, with a mean time to fracture union of 12-18 weeks. In recent studies, the use of bone marrow cells has been introduced to accelerate healing of fractures with union problems. The aim of this randomized trial is to determine if operative treatment of MT-V stress fractures with use of concentrated blood and bone marrow aspirate (cB + cBMA) is more effective than surgery alone. We hypothesize that using cB + cBMA in the operative treatment of MT-V stress fractures will lead to an earlier fracture union. METHODS/DESIGN: A prospective, double-blind, randomized controlled trial (RCT) will be conducted in an academic medical center in the Netherlands. Ethics approval is received. 50 patients will be randomized to either operative treatment with cB + cBMA, harvested from the iliac crest, or operative treatment without cB + cBMA but with a sham-treatment of the iliac crest. The fracture fixation is the same in both groups, as is the post-operative care.. Follow up will be one year. The primary outcome measure is time to union in weeks on X-ray. Secondary outcome measures are time to resumption of work and sports, functional outcomes (SF-36, FAOS, FAAM), complication rate, composition of osteoprogenitors in cB + cBMA and cost-effectiveness. Furthermore, a bone biopsy is taken from every stress fracture and analysed histologically to determine the stage of the stress fracture. The difference in primary endpoint between the two groups is analysed using student's t-test or equivalent. DISCUSSION: This trial will likely provide level-I evidence on the effectiveness of cB + cBMA in the operative treatment of MT-V stress fractures. TRIAL REGISTRATION: Netherlands Trial Register (reg.nr NTR4377 ).

[Analysis of total cost of treatment of patients with inflammatory bowel diseases].

The article stresses that among the chronic diseases of the digestive tract occupy a special place inflammatory bowel disease (IBD)--UC and BC with multiple complications and the onset of early disability of patients. IBD is a serious issue of gastroenterology, since their etiology remains unknown, and specific treatment hasn't yet been developed. Finally, the prevalence and social significance of IBD also occupy a leading place among the diseases of the digestive organs, since they are characterized by recurrent course and have adverse medical and social prognosis. According to sources in various countries annually spend huge money for treatment of IBD. The costs of IBD depends on the severity and nature of complications, duration of illness, the choice of treatment, frequency of hospitalization and the patient's country of residence. Various studies demonstrate the feasibility of using more modern efficient methods of treatment (MSSC + therapy) to reduce the incidence of complications associated with IBD, resulting in huge costs.

[Pharmacoeconomic benefits of patients with ulcerative colitis treatment with help of mesenchymal stem cells].

UNLABELLED: The aim of the study was to develop economically motivated decision to use MSSK therapy in patients with colitis (UC). In accordance with the intended purpose it was necessary to determine the effect of MSSK transplantation on clinical and morphological characteristics of the UC, and evaluate the safety and cost-effectiveness of this therapy for the patient. MATERIAL AND METHODS: The study included 39 patients with ulcerative colitis--UC (1 group). In the comparison group (2 nd group) were included 30 patients with UC. For 2-3 days prior to the MSSK induction was terminated immunosuppressants, was reduced the dose of corticosteroids to 15-20 mg/and day dose of aminosalicylate was left at the level of 2.0 g/day. To quantify the results were used the average values of indices of Rachmilevitz clinical activity, Mayo and Geb's scales. Monitoring of patients continued to terms ranging from 4 to 8 months. Bone marrow cells were obtained from the sternum or the iliac crest donor. Cultivation was carried out for 5-6 weeks, than we received an allogeneic MSSK donor population in the number (1,5-2) x 108 cells needed for patient transplant. The culture of MSCs were injected in the drip i.v. at once. Clinical activity was assessed UC scored using an Rachmilevitz index. Endoscopic picture of UC was assessed with help of a Mayo scale. Assessment of histological UC preparations was conducted on a Geb's scale. Was conducted pharmacoeconomic analysis (direct costs and cost-effectiveness) of the MSSK-therapy of patients with UC that were compared with standard therapy. CONCLUSION: Most adult patients with UC are economically active population. Average cost (direct costs) of standard and MSSK-therapy patients with UC in the hospital (direct costs) amounted to 26645,9 +/- 1776,1 and 35395 +/- 6532,1 rubles, respectively. Patients with UC after applying MSSK noted a statistically significant reduce of clinical and morphological indices of inflammatory process activity and decrease in frequency of relapses compared to standard therapy. This was accompanied by a decline in demand for glucocorticosteroid and others LP and contributed to additional savings of treatment costs. Transplantation MSSK can be evaluated as a new strategic direction in the therapy of IBD is very relevant, at least in Russia.