The costs of rheumatoid arthritis

The economic costs associated with rheumatoid arthritis (RA), a chronic, systemic, inflammatory disorder that affects many joints, are high, approximating those of coronary heart disease. The estimated prevalence of RA in the US is 0.9%. Incidence increases with age, and is highest among women in the fourth to sixth decades of life. The primary impact of RA is due to the significant morbidity associated with this disease. Mortality is increased among a poorly defined subgroup of RA patients. The average level of disability among RA patients is moderate, but 6.5 to 12% of patients are severely disabled. Between one- and two-thirds of previously employed patients have a reduced work capacity. Treatment primarily involves the use of nonsteroidal anti-inflammatory drugs and disease modifying antirheumatic drugs. Rehabilitation measures and orthopaedic surgery are also used. Total annual direct costs of RA (total charges) have been calculated to be $US5275 and $US6099 (1991 dollars) per patient. Lifetime medical care charges were estimated at $US12,578 per patient (1991 dollars). The direct costs of RA are substantial, but indirect costs have been calculated to be much higher because of extensive morbidity. The difference between the direct and indirect costs of RA is decreasing because salary increases have not kept pace with rising healthcare costs. The latter are increasing rapidly in RA because of the use of new technology, surgical procedures, and the greater use of drugs with frequent monitoring requirements and significant toxicity. Because intangible costs such as pain form a substantial part of the overall costs of RA but are difficult to evaluate, cost estimates inevitably underestimate the impact of the disease on individuals and society.     

Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis

Nabumetone is a nonsteroidal anti-inflammatory prodrug, which exerts its pharmacological effects via the metabolite 6-methoxy-2-naphthylacetic acid (6-MNA). Nabumetone itself is non-acidic and, following absorption, it undergoes extensive first-pass metabolism to form the main circulating active metabolite (6-MNA) which is a much more potent inhibitor of preferentially cyclo-oxygenase (COX)-2. The three major metabolic pathways of nabumetone are O-demethylation, reduction of the ketone to an alcohol, and an oxidative cleavage of the side-chain occurs to yield acetic acid derivatives. Essentially no unchanged nabumetone and < 1% of the major 6-MNA metabolite are excreted unchanged in the urine from which 80% of the dose can be recovered and another 10% in faeces. Nabumetone is clinically used mainly for the management of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) to reduce pain and inflammation. The clinical efficacy of nabumetone has also been evaluated in patients with ankylosing spondylitis, soft tissue injuries and juvenile RA. The optimum oral dosage of nabumetone for OA patients is 1 g once daily, which is well tolerated. The therapeutic response is superior to placebo and similar to nonselective COX inhibitors. In RA patients, nabumetone 1 g at bedtime is optimal, but an additional 0.5-1 g can be administered in the morning for patients with persistent symptoms. In RA, nabumetone has shown a comparable clinical efficacy to aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen. Clinical trials and a decade of worldwide safety data and long-term postmarketing surveillance studies show that nabumetone is generally well tolerated. The most frequent adverse effects are those commonly seen with COX inhibitors, which include diarrhoea, dyspepsia, headache, abdominal pain and nausea. In common with other COX inhibitors, nabumetone may increase the risk of GI perforations, ulcerations and bleedings (PUBs). However, several studies show a low incidence of PUBs, and on a par with the numbers reported from studies with COX-2 selective inhibitors and considerably lower than for nonselective COX inhibitors. This has been attributed mainly to the non-acidic chemical properties of nabumetone but also to its COX-1/COX-2 inhibitor profile. Through its metabolite 6-MNA, nabumetone has a dose-related effect on platelet aggregation, but no effect on bleeding time in clinical studies. Furthermore, several short-term studies have shown little to no effect on renal function. Compared with COX-2 selective inhibitors, nabumetone exhibits similar anti-inflammatory and analgesic properties in patients with arthritis and there is no evidence of excess GI or other forms of complications to date.     

Economic evaluation of etoricoxib versus non-selective NSAIDs in the treatment of osteoarthritis and rheumatoid arthritis patients in the UK

INTRODUCTION: The objective of this study was to evaluate the potential economic implications of using etoricoxib versus non-selective NSAID alternatives in the treatment of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in the UK. STUDY DESIGN: Decision-analytical modelling was used to calculate the expected costs and consequences of the use of etoricoxib compared with non-selective NSAIDs alone, NSAIDs plus proton pump inhibitors (PPIs), NSAIDs plus histamine H2 receptor antagonists and NSAIDs plus misoprostol over a continuous treatment period of 1 year. METHODS: The model considered direct medical costs from the perspective of the UK National Health Service (NHS) and used data from phase IIb and III clinical trials of etoricoxib to determine probabilities of gastrointestinal (GI) events. Model outcomes were defined as resource-consuming GI-related events, including clinically evident gastroduodenal perforations, symptomatic gastroduodenal ulcers, or upper GI bleeding (collectively, PUBs ['perforation, ulcers and/or bleeding']). Resource utilisation and costs (2002 values) for the treatment of OA and RA as well as GI events were based on published literature and information available from UK-specific sources. MAIN OUTCOME MEASURES AND RESULTS: The model suggests that etoricoxib is cost saving compared with non-selective NSAIDs plus PPIs or non-selective NSAIDs plus misoprostol. The model also suggests that etoricoxib is cost effective in terms of the incremental cost per QALY gained for non-selective NSAIDs alone (pound 19,766) and for non-selective NSAIDs plus H2 antagonists (pound 9350). The incremental cost of etoricoxib per PUB avoided was pound 12,446 versus non-selective NSAIDs alone and pound 6438 versus NSAIDs co-prescribed with H2 antagonists. For patients without the presence of specific GI risk factors (history of GI event, corticosteroid use or disability), etoricoxib may be cost effective for patients over age 56 years, assuming a cost-effectiveness threshold of pound 30,000 per QALY gained. Etoricoxib may also be cost effective in patients of all ages who had at least one specific GI risk factor. CONCLUSIONS: The model suggests, with its underlying assumptions and data, that etoricoxib is a cost-effective alternative to therapeutic regimens involving non-selective NSAIDs for OA or RA, from the UK NHS perspective. Etoricoxib may be cost saving and dominant over non-selective NSAIDs used together with a PPI or misoprostol. When compared with non-selective NSAIDs alone or non-selective NSAIDs co-prescribed with H2 antagonists, the incremental cost per QALY gained with use of etoricoxib was within the generally accepted threshold for cost effectiveness (less than pound 30,000 per QALY gained).     

Variation in the use of biologics in the management of rheumatoid arthritis across the UK

Abstract

Objectives:

Treatment options for rheumatoid arthritis (RA) include conventional synthetic disease-modifying antirheumatic drugs (sDMARDs) and newer biologic DMARDs (biologics). This study describes treatment patterns, adherence to guidance and outcomes at hospital/regional level in the UK.     

Cost study of NSAID use in rheumatoid arthritis based on recent therapeutic protocols

In today's health care beside the medical perspective, economic aspects should also be taken into consideration. Because of the significant opportunity-cost, only the most cost-effective techniques should be subsidized, which result the highest net-benefit for the society. This paper focuses on the economic aspects of the chronic NSAID use in rheumatoid arthritis. Based on recent therapeutic protocols a cost study (partial economic evaluation) was carried out. Our results indicate that for patients with an average GI-risk retard diclofenac could be a possible good choice. For patients with moderate to severe GI risk, retard diclofenac + pantoprazole combination therapy should be prescribed. COX-2 inhibitors are advised only for a limited group of patients with specific conditions; because of their higher price and side effect profile (severe CV adverse effect and uncertain GI benefits). We would also highlight the importance of individual therapy. In complex our purpose was to evaluate current therapeutic guidelines from a pharmacoeconomic perspective.     

Pharmacological management of juvenile rheumatoid arthritis.

The goals of pharmacotherapy in juvenile rheumatoid arthritis (JRA) are to suppress chronic synovitis which causes potential cartilage destruction and deformities, to control the systemic effects of inflammation (including growth retardation and nutritional deficits), relieve pain and limit psychological impact of disease. Currently available methods include nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, salicylates, naproxen, tolmetin, ibuprofen and indomethacin; disease modifying antirheumatic drugs (DMARDs) such as oral and injectable gold salts, hydroxychloroquine, penicillamine, oral and injectable methotrexate, and sulfasalazine; oral (daily or on alternate days), intravenous pulse or intra-articular corticosteroids; immunosuppresants, including cyclophosphamide, chlorambucil, cyclosporin, and azathioprine; and gammaglobulin and other experimental therapies. Over the past 10 years, rheumatologists have adopted more aggressive pharmacological treatment of JRA. As time progresses and the safety of certain drugs such as methotrexate and sulfasalazine becomes clearer, wider and earlier use of these agents can be expected. Still the approach to treatment is a 'step by step' one, starting with the classical NSAIDs and ending with the DMARDs as needed.     

氯诺昔康治疗类风湿关节炎和骨性关节炎41例

目的:研究氯诺昔康治疗类风湿关节炎和骨性关节炎的疗效及安全性.方法:类风湿关节炎(34例)和骨性关节炎(48例)所致膝关节疼痛患者分别随机双盲分成2组,试验组(n=41)行膝关节腔注射氯诺昔康(8mg,每周1次),对照组(n=41)用安慰剂,疗程为3周.对二药治疗前后的疼痛指数进行比较.结果:试验组和对照组在治疗3周后的平均疼痛指数分别减少31.80和8.20(P＜0.05),显示氯诺昔康对关节炎的疼痛有显著疗效.2组不良事件发生率分别为7.31%和4.87%,均无严重不良事件发生.结论:氯诺昔康对类风湿关节炎和骨性关节炎具有良好的镇痛抗炎作用,且耐受性良好.     

心理护理对类风湿关节炎患者的影响

目的分析心理护理对类风湿性关节炎患者的影响。方法将52例类风湿性关节炎患者随机分为治疗组和对照组各26例。对照组给予常规护理,治疗组在此基础上给予针对性的心理护理。观察2组复发率及患者满意度。结果 2组均获随访0.5～2年,治疗组复发率低于对照组,满意度高于对照组,差异均有统计学意义(P<0.05或P<0.01)。结论对类风湿性关节炎患者进行心理护理,可降低致残率,提高患者的生活质量,缩短康复时间,值得临床推广应用。     

Biological response modifiers in the management of rheumatoid arthritis.

The management of rheumatoid arthritis (RA) with biological response modifiers (BRMs) is reviewed. RA, an autoimmune disorder affecting 1-2% of the world's population, is characterized by inflammation of synovial tissues, joint swelling, stiffness, and pain that may progress to joint erosion. There is strong evidence that inflammatory mediators, such as tissue necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), play a critical role in the pathogenesis of this disorder. IL-1-receptor antagonist (IL-1Ra) is produced in healthy subjects and helps to protect against the adverse effects associated with IL-1 overexpression. Administration of IL-1Ra or similar agents may reduce the effects of IL-1 and ameliorate inflammatory conditions. Traditional treatment of RA has been based on symptomatic management with non-steroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, and corticosteroids, each of which has substantial drawbacks in terms of effectiveness or adverse effects. Newer therapeutic strategies for blocking the biological effects of inflammatory cytokines include antibodies directed against TNF (e.g., infliximab), soluble receptors (e.g., etanercept) and receptor antagonists to IL-1 (anakinra) [corrected]. Clinical trials indicate that these BRMs may be more effective than traditional agents because they are able to alter joint remodeling in addition to attenuating symptoms. Anti-TNF therapies may be associated with increased risk for infections, sepsis, tuberculosis reactivation, demyelination disorders, and blood dyscrasias; anakinra appears to be safer. Combination therapy with BRMs may be more appropriate for RA than monotherapy. The role of BRMs in the treatment of RA will evolve as investigators learn more about the drugs and the disorder.     

尼美舒利治疗骨关节炎和类风湿关节炎的临床疗效

目的：了解尼美舒利治疗骨关节炎（ＯＡ）及类风湿关节炎（ＲＡ）的疗效及副作用。方法：尼美舒利组：ＯＡ和ＲＡ各３０例，予尼美舒利１００ｍｇ，ｐｏ，ｂｉｄ；对照组：ＯＡ和ＲＡ各３０例，予双氯芬酸２５ｍｇ，ｐｏ，ｔｉｄ，或萘普生２５０ｍｇ，ｐｏ，ｂｉｄ，观察４ｗｋ。结果：治疗前后２组病人各项临床指标均有明显改善；而实验室指标改善不明显（Ｐ＞０．０５）。２组总有效率分别是８８％和８５％，差别无显著意义；副作用发生率分别为３％和１３％，差别有显著意义（Ｐ＜０．０５）。结论：尼美舒利抗炎镇痛疗效肯定，副作用较少，是一种安全性较佳的非甾体类消炎止痛药。     

怡美力治疗类风湿关节炎和骨关节炎的疗效观察

目的 :观察新型非甾体消炎止痛药怡美力治疗类风湿关节炎和骨关节炎的疗效和不良反应。方法 :80例类风湿关节炎病人随机分为治疗组 5 0例 ,对照组 30例。 40例骨关节炎病人分为治疗组 2 0例 ,对照组 2 0例。治疗组服怡美力 10 0mg ,po ,bid× 4wk ;对照组服双氯芬酸钠 2 5mg ,po,tid× 4wk。 结果 :在治疗组中类风湿关节炎组和骨关节炎组的疗效分别为 84%和80 % ,对照组为 83.33 %和 80 % ,两组无显著差异 (P >0 .0 5 )。不良反应发生率治疗组和对照组分别为 13.75 %和 30 % ,治疗组明显低于对照组 (P <0 .0 5 )。结论 :怡美力是一种安全有效的新型非甾体消炎止痛药。     

Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis

Rofecoxib is a selective cyclo-oxygenase (COX)-2 inhibitor which has little or no effect on the COX-1 isoenzyme at doses up to 1000 mg/day. Rofecoxib has greater selectivity for COX-2 than celecoxib, meloxicam, diclofenac and indomethacin. In well-controlled clinical trials, rofecoxib 12.5 to 500 mg/day has been evaluated for its efficacy in the treatment of osteoarthritis, acute pain and rheumatoid arthritis [lower dosages (5 to 125 mg/day) were generally used in the chronic pain indications]. In the treatment of patients with osteoarthritis, rofecoxib was more effective in providing symptomatic relief than placebo, paracetamol (acetaminophen) and celecoxib and was similar in efficacy to ibuprofen, diclofenac, naproxen and nabumetone. Overall, both the physician's assessment of disease status and the patient's assessment of response to therapy tended to favour rofecoxib. In patients with postsurgical dental pain, pain after spinal fusion or orthopaedic surgery, or primary dysmenorrhoea, rofecoxib provided more rapid and more sustained pain relief and reduced requirements for supplemental morphine use after surgery than placebo. Rofecoxib was more efficacious than celecoxib in patients with acute dental pain and pain after spinal fusion surgery, although celecoxib may have been used at a subtherapeutic dose. In comparison with traditional nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen, diclofenac and naproxen sodium, rofecoxib was similar in efficacy in the treatment of acute pain. Although naproxen sodium provided more rapid pain relief than rofecoxib in patients with primary dysmenorrhoea, the reverse was true after orthopaedic surgery: rofecoxib provided more rapid pain relief and less supplemental morphine was needed. Rofecoxib was as effective as naproxen in providing symptomatic relief for over 8700 patients with rheumatoid arthritis. Compared with traditional NSAID therapy, rofecoxib had a significantly lower incidence of endoscopically confirmed gastroduodenal ulceration and, in approximately 13,000 patients with osteoarthritis and rheumatoid arthritis, a lower incidence of gastrointestinal (GI) adverse events. Rofecoxib was generally well tolerated in all indications with an overall tolerability profile similar to traditional NSAIDs. The most common adverse events in rofecoxib recipients were nausea, dizziness and headache. In conclusion, rofecoxib is at least as effective as traditional NSAID therapy in providing pain relief for both chronic and acute pain conditions. Rofecoxib provides an alternative treatment option to traditional NSAID therapy in the management of symptomatic pain relief in patients with osteoarthritis. Initial data from patients with primary dysmenorrhoea and postoperative pain are promising and further trials may confirm its place in the treatment of these indications. Rofecoxib has also shown promising results in patients with rheumatoid arthritis and is likely to become a valuable addition to current drug therapy for this patient population. Importantly, rofecoxib is associated with a lower incidence of GI adverse events than traditional NSAIDs making it a primary treatment option in patients at risk of developing GI complications or patients with chronic conditions requiring long term treatment.     

Open-label tolerability study of enteric-coated naproxen in the treatment of osteoarthritis and rheumatoid arthritis.

Two hundred and ninety-six patients were enrolled in a 6-month, open-label tolerability study of enteric-coated naproxen in patients with rheumatoid arthritis (n = 174) and osteoarthritis (n = 122). Thirty percent of the patients were greater than 65 years of age. Under standard clinical prescribing conditions, enteric-coated naproxen 500 mg twice daily and 375 mg twice daily demonstrated an acceptable tolerability profile that was not different from what one would expect with standard naproxen.     

The cost effectiveness of infliximab for severe treatment-resistant rheumatoid arthritis in the UK

OBJECTIVE: To estimate the cost effectiveness (from the UK NHS and personal social service perspectives) of infliximab plus methotrexate (MTX) compared with MTX alone, in the treatment of patients with severe rheumatoid arthritis (RA) who were not adequately controlled on disease-modifying antirheumatic drugs and who were resistant to MTX. METHOD: Clinical data for the first year of therapy were taken from the ATTRACT (Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy) and a Markov model developed to assess costs and consequences in the longer term. Transition probabilities and health state valuations for the model were estimated based on the ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) cohort, and resource use and costs ( 2,000 pounds values) obtained from various sources in the UK. Univariate sensitivity analyses were conducted to test the robustness of the results. RESULTS: The primary analysis suggested that infliximab plus MTX had an ICER of 33,618 pounds per QALY gained. Alternative modelling assumptions and various other sensitivity analyses were applied, but the ICER always remained within the range for interventions typically funded by the NHS. CONCLUSION: This model suggests, with its underlying assumptions and data, that the combination of infliximab and MTX may be a cost-effective treatment (from the UK NHS and personal social service perspectives) for patients experiencing RA that cannot be maintained on MTX alone.     

The positive effect of pregnancy in rheumatoid arthritis and the use of medications for the management of rheumatoid arthritis during pregnancy

Inflammopharmacology - Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disorder that is mostly characterised by progressive symmetrical joint destruction, particularly in the wrist...     

尼美舒利治疗类风湿关节炎和骨性关节炎的临床研究

目的：观察国产尼美舒利对类风湿关节炎（ＲＡ）和骨性关节炎（ＯＡ）的疗效和安全性。方法：选取ＲＡ患者５９ 例和ＯＡ患者４４ 例。ｐｏ 尼美舒利片１００ ｍｇ,ｂｉｄ;对照组ｐｏ 布洛芬缓释胶囊３００ｍｇ,ｂｉｄ。治疗时间为４ｗｋ。分别观察治疗前后临床指标和炎性实验指标的变化。结果：尼美舒利治疗ＲＡ４ｗｋ 后,疼痛程度、压痛关节数、关节压痛指数、关节肿胀指数、握力、晨僵时间、血沉均显著改善。对ＲＡ的总有效率为８３．３％ 。治疗ＯＡ４ｗｋ 后,膝关节活动痛、１５ｍ 行走时间、日常活动能力及病人综合评估均有显著改善。对ＯＡ的总有效率为７５．０％ 。其不良反应总发生率为１９．２％ , 以胃肠道反应为常见（９．６％）。尼美舒利对ＲＡ和ＯＡ的疗效及不良反应的发生率与布洛芬相比均无显著性差异。结论：尼美舒利对ＲＡ和ＯＡ的疗效及不良反应的发生率均与布洛芬相当。     

氟比洛芬治疗类风湿关节炎、骨关节炎及强直性脊柱炎

目的 :观察氟比洛芬治疗类风湿关节炎、骨关节炎及强直性脊柱炎的疗效和不良反应。方法 :80例类风湿关节炎病人随机分为氟比洛芬组 50例 ,双氯芬酸组 30例。 4 0例骨关节炎病人分为氟比洛芬组 2 0例 ,双氯芬酸组 2 0例。氟比洛芬组口服氟比洛芬 50mg ,po ,tid× 4wk ;双氯芬酸组口服双氯芬酸 2 5mg ,po ,tid× 4wk。 38例强直性脊柱炎均为氟比洛芬组 ,口服氟比洛芬 10 0mg ,po ,tid×4wk。结果 :在氟比洛芬组中类风湿关节炎组和骨关节炎组的疗效分别为 86%和 85% ,双氯芬酸组为87%和 80 % ,2组差异无显著意义 (P >0 .0 5)。强直性脊柱炎组的疗效为 79%。不良反应发生率氟比洛芬组和双氯芬酸组分别为 19%和 30 % ,氟比洛芬组明显低于双氯芬酸组 (P <0 .0 5)。结论 :氟比洛芬是一种安全有效的新型非甾体消炎止痛药