Objective Osteoarthritis (OA) affects 10% of adults in the UK. Despite over one-third of people with OA experiencing chronic pain, few studies have examined the population-level impact of chronic pain associated with OA. We compared resource-use and epidemiological outcomes in patients with mild, moderate and severe chronic OA-associated pain and matched controls without known OA.Design Retrospective, longitudinal, observational cohort study (July 2008 to June 2019).Setting Electronic records extracted from Clinical Practice Research Datalink GOLD primary care linked to Hospital Episode Statistics (HES).Participants Patients (cases; n=23 016) aged ≥18 years with chronic OA-associated pain. Controls (n=23 016) without OA or chronic pain matched on age, sex, comorbidity burden, general practitioner practice and available HES data.Interventions None.Primary and secondary outcome measures Total healthcare resource use (HCRU), direct healthcare costs in 0–12, 12–24 and 24–36 months postindex. Secondary outcomes included incidence and prevalence of chronic OA-associated pain and pharmacological management.Results HCRU was consistently greater in cases versus controls for all resource categories during preindex and postindex periods. Across follow-up periods, resource use was greatest in patients with severe pain. In the first 12 months postindexing, mean total costs incurred by cases were four times higher versus matched controls (£256 vs £62); costs were approximately twice as high in cases vs controls for months 12–24 (£166 vs £86) and 24–36 (£150 vs £81; all p<0.0001). The incidence of new cases of chronic pain associated with OA was 2.64 per 1000 person-years; the prevalence was 1.4%.Conclusions This study highlights the real-world cost of chronic pain associated with OA in cases versus matched controls. We included patients with mild, moderate and severe pain associated with OA, and showed HCRU in discrete 1-year time frames. The true economic burden of pain associated with OA is likely to be considerably higher when indirect costs are considered.

ObjectiveDespite the prevalence of osteoarthritis (OA) in England, few studies have examined the health economic impact of chronic pain associated with OA. The aim of this study was to compare outcomes in patients with moderate-to-severe chronic pain associated with OA and matched controls without known OA.DesignRetrospective, longitudinal, observational cohort study.SettingElectronic records extracted from the Clinical Practice Research Datalink GOLD primary care database linked to Hospital Episode Statistics (HES) data set.ParticipantsPatients (cases; n=5931) ≥18 years and with existing diagnosis of OA and moderate-to-severe pain associated with their OA, and controls matched on age, sex, comorbidity burden, general practitioner (GP) practice and availability of HES data.InterventionsNone.Primary and secondary outcome measuresTotal healthcare resource use (HCRU) and direct healthcare costs during 0–6, 0–12, 0–24 and 0–36 months of follow-up. Secondary outcomes measures included pharmacological management and time to total joint replacement.ResultsPatients with moderate-to-severe chronic pain associated with OA used significantly more healthcare services versus matched controls, reflected by higher HCRU and significantly higher direct costs. During the first 12 months’ follow-up, cases had significantly more GP consultations, outpatient attendances, emergency department visits and inpatient stays than matched controls (all p<0.0001). Total mean costs incurred by cases during 0–12 months’ follow-up were five times higher in cases versus controls (mean (SD): £4199 (£3966) vs £781 (£2073), respectively). Extensive cycling through pharmacological therapies was observed; among cases, 2040 (34.4%), 1340 (22.6%), 841 (14.2%), 459 (7.7%) and 706 (11.9%) received 1–5, 6–10, 11–15, 16–20 and >20 lines of therapy, respectively.ConclusionsThis wide-ranging, longitudinal, observational study of real-world primary and secondary care data demonstrates the impact of moderate-to-severe chronic pain associated with OA in patients compared with matched controls. Further studies are required to fully quantify the health economic burden of moderate-to-severe pain associated with OA.

Objective:Despite the high prevalence of chronic low back pain (CLBP) and osteoarthritis (OA), few estimates of the economic cost of these conditions in England have been published. The aim of the present analysis was to characterise the economic burden of moderate-to-severe pain associated with CLBP + OA and CLBP alone compared with general population-matched controls without CLBP or OA. The primary objective was to describe the total healthcare resource use (HCRU) and direct healthcare costs associated with the target patient populations. Secondary objectives were to describe treatment patterns and surgical procedures.Methods:This was a retrospective, observational cohort study of patients receiving healthcare indicative of moderate-to-severe chronic pain associated with CLBP, with or without OA. We used linked longitudinal data from the Clinical Practice Research Datalink GOLD and Hospital Episode Statistics (HES). Patients (cases) were matched 1 : 1 with controls on age, sex, comorbidity burden, GP practice, and HES data availability.Results:The CLBP-alone cohort comprised 13 554 cases with CLBP and 13 554 matched controls; the CLBP + OA cohort comprised 7803 cases with both OA and CLBP and 7803 matched controls. Across all follow-up periods, patients with CLBP alone and those with CLBP + OA had significantly more GP consultations, outpatient attendances, emergency department visits, and inpatient stays than controls (all p < 0.0001). By 36 months after indexing, the mean (SD) per-patient total direct healthcare cost in the CLBP-alone cohort was £5081 (£5905) for cases and £1809 (£4451) for controls (p < 0.0001); in the CLBP + OA cohort, the mean (SD) per-patient total direct healthcare cost was £8819 (£7143) for cases and £2428 (£4280) for controls (p < 0.0001).Conclusion:Moderate-to-severe chronic pain associated with CLBP-with or without OA-has a substantial impact on patients and healthcare providers, leading to higher HCRU and costs versus controls among people with CLBP alone or together with OA.

Due to limitations of existing pharmacological therapies for the management of chronic pain in osteoarthritis (OA), surgical interventions remain a major component of current standard of care, with...

To estimate the cumulative incidence of colectomy for ulcerative colitis (UC) patients in the UK, and the risk of perioperative complications and mortality. A literature review was conducted using Medline. Search keywords included UC, terms for surgical interventions such as colectomy, proctocolectomy, ileal pouch anal anastomosis, ileoanal pouch, pouch surgery, ileorectal anastomosis, and ileostomy. Paediatric population studies were excluded. In addition, the review considered data from the UK inflammatory bowel disease (UK IBD) audits in 2012 and 2014. The Medline search identified 310 unique records. Nine studies reported data on UK patients. Five of them considered only emergency operations for the management of acute exacerbations. From the remaining four records, two publications reported data from large, population-based studies, with 15 and 20 years of patient follow-up. The evidence suggested a linear increase in the incidence after the first 5 years since diagnosis. The cumulative probability of colectomy ranged from 6.9% over 15 years in one study to 8.3% and 11.2% at 10 and 20 years since diagnosis in the second study. This cumulative risk was lower, but broadly within the range of colectomy incidence rates presented by other studies from Norway or a multi-country meta-analysis of population-based studies for surgery in inflammatory bowel diseases. The UK IBD reported complications among 32% and 35% of patients undergoing elective and non-elective surgery respectively, with wound infection being the most common event. The overall mortality was reported to be reduced by 19% between two consecutive versions of the audit: 0.92% (28/3049) in 2010-2012 and 0.75% (30/3987) in 2012-2014. Colectomy is still the last option for UC patients with an inadequate response to pharmacological treatments. The cumulative probability of colectomy, since diagnosis of UC, showed a steady increase but remained in comparable levels with other non-UK studies.

To compare the clinical efficacy and safety of tofacitinib, an orally administered small molecule therapy, with approved biologic therapies for the treatment of moderately to severe active ulcerative colitis (UC). A systematic review was conducted to identify randomised controlled trials (RCTs) reporting pre-defined efficacy and safety endpoints for tofacitinib or biological therapies (adalimumab, golimumab, infliximab and vedolizumab). Clinical response and clinical remission after a short-term induction phase (6-10 weeks) and at the end of a longer-term maintenance phase (52-60 weeks) were evaluated using a random effects Bayesian multinomial likelihood model with probit link. Patients with and without prior exposure to TNF inhibitor (TNFi) drugs were considered separately. Sensitivity analyses tested alternatives to the population inclusion criteria (TNFi-failure vs TNFi-exposure) and clinical endpoints (centrally versus locally assessed endoscopic sub-scores). Safety outcomes, including serious infections, were also explored. The network meta-analyses (NMA) adhered to NICE-recommended methods. Searches of Medline, Embase and Cochrane were last performed April 2019. Seventeen RCTs were included in the NMAs. No statistically significant differences between biological therapies and tofacitinib for either TNFi-naïve or TNFi-exposed patients were observed. In TNFi-naïve patients, all therapies were more efficacious than placebo, with infliximab, vedolizumab and tofacitinib ranked best in induction and tofacitinib, vedolizumab and golimumab ranked best in maintenance. In TNFi-exposed patients, only tofacitinib was significantly more efficacious than placebo as induction therapy, and only tofacitinib and vedolizumab were significantly more efficacious as maintenance therapies. Results of the NMA sensitivity analyses were consistent with the base case. There were no significant differences in serious infection rates among therapies. This study provides a contemporary and robust assessment of the relative efficacy and safety of targeted therapies for patients with UC, with specific regard for TNFi-naïve and TNFi-exposed subgroups. These results show that tofacitinib is efficacious in both populations.

Ulcerative colitis (UC) is a chronic inflammatory condition of the colon which has a major impact on patients' health related quality of life and a substantial burden on health care budgets. The objective of this analysis was to evaluate the cost-effectiveness of tofacitinib and other approved biologic therapies for the treatment of moderately to severe active UC in the United Kingdom. A Markov model compared the lifetime costs and consequences of treatment with tofacitinib, adalimumab, golimumab, infliximab, vedolizumab and conventional therapy. The analysis took a National Health Service (NHS) perspective and measured benefits in quality-adjusted life years (QALYs). Patients transitioned between health states (defined by treatment and level of disease control) based on results of a network meta-analysis of clinical response and clinical remission. Utility values and estimates of resource use were sourced from systematic reviews of the published literature. Drug, disease monitoring, adverse event and colectomy costs were obtained from UK sources. Analyses were conducted separately for patients with and without prior TNF inhibitor (TNFi) exposure. Deterministic and probabilistic sensitivity analysis were undertaken. The incremental cost-effectiveness ratios for tofacitinib versus conventional therapy were £21,338 and £22,816 per QALY in the TNFi-naïve and TNFi-exposed populations, respectively. TNFi therapies were dominated or extendedly dominated in both populations. Compared with vedolizumab, tofacitinib generated a similar number of QALYs at a lower cost. Results were most sensitive to variation in response and remission rates and to costs of conventional therapy and serious infections. Probabilistic sensitivity analysis showed that tofacitinib had the highest likelihood of being cost effective at a threshold of £30,000 per QALY: 54% and 46% in in TNFi-naïve and TNFi-exposed patients, respectively. Tofacitinib is an efficacious treatment for moderately to severely active UC and is likely to be a cost-effective use of NHS resources.

Background and aims In the UK, treatments for patients with moderately to severely active ulcerative colitis who have an inadequate response to conventional therapies comprise four biological therapies—the tumour necrosis factor inhibitor (TNFi) agents adalimumab, golimumab and infliximab and the anti-integrin vedolizumab—and an orally administered small molecule therapy, tofacitinib. However, there have been few head-to-head studies of these therapies. This study aimed to compare the clinical and cost-effectiveness of tofacitinib with biological therapies. Methods A systematic literature review was conducted to identify all relevant randomised controlled trial (RCT) evidence. Clinical response, clinical remission and serious infection rates were synthesised using network meta-analysis (NMA). The results were used to compare the cost-effectiveness of tofacitinib and biologics with conventional therapy, using a Markov model, which incorporated lifetime costs and consequences of treatment from a UK National Health Service perspective. Analyses were conducted separately for TNFi-naïve and TNFi-exposed populations. Results Seventeen RCTs were used in the NMAs. There were no statistically significant differences among biological therapies and tofacitinib for either TNFi-naïve or TNFi-exposed patients. In TNFi-naïve patients, all therapies were more efficacious than placebo. In TNFi-exposed patients, only tofacitinib was significantly more efficacious than placebo as induction therapy, and only tofacitinib and vedolizumab were significantly more efficacious than placebo as maintenance therapies. There were no significant differences in serious infection rates among therapies. The incremental cost-effectiveness ratios for tofacitinib versus conventional therapy were £21 338 and £22 816 per quality-adjusted life year (QALY) in the TNFi-naïve and TNFi-exposed populations, respectively. TNFi therapies were dominated or extendedly dominated in both populations. Compared with vedolizumab, tofacitinib was associated with a similar number of QALYs, at a lower cost. Conclusion Tofacitinib is an efficacious treatment for moderately to severely active ulcerative colitis and is likely to be a cost-effective use of NHS resources.