Failure Of Disease-modifying Antirheumatic Drugs Research Articles

Clinical characteristics associated with drug-free sustained remission in patients with rheumatoid arthritis: Data from Korean Intensive Management of Early Rheumatoid Arthritis (KIMERA)

ObjectivesThere is limited information on treatment withdrawal in patients with rheumatoid arthritis (RA). This study investigated the clinical course after stopping disease-modifying anti-rheumatic drugs (DMARDs) in patients with well-controlled RA and the clinical features associated with disease flare. MethodsAmong patients in the Korean Intensive Management of Early Rheumatoid Arthritis (KIMERA) cohort, discontinuation of DMARDs was determined by a shared decision between patient and rheumatologist. Drug-free remission was defined as (1) non-use of DMARDs and corticosteroids, (2) Disease Activity Score in 28 joints (DAS28) <2.6, and (3) no evidence of synovitis. The maintenance rate of drug-free remission and the predictors for flare were evaluated using Cox proportional hazard models. ResultsOf 234 patients, 50 patients discontinued DMARDs. All but one using etanercept were treated with conventional synthetic DMARDs. The median follow-up duration was 30 months, and 31 patients (62%) experienced disease flare after stopping DMARDs. The maintenance rate of drug-free remission was 94.0%, 86.7%, and 46.1% at 12, 24, and 48 months, respectively. Disease flare was correlated with longer time to remission, failure of initial DMARDs, and longer duration of disease and higher disease activity at DMARD withdrawal (P = 0.001, 0.022, 0.010 and 0.037, respectively). In multivariate analyses, longer duration of disease (>24 months) and higher disease activity (DAS28 >2.26) at DMARD withdrawal was independently associated with disease flare. ConclusionDrug-free remission was feasible in selected patients with well-controlled RA. Patients with early RA and lower disease activity at DMARD withdrawal are more likely to maintain the drug-free remission.

Serum P-glycoprotein level: a potential biomarker of DMARD failure in patients with rheumatoid arthritis.

To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). A cross-sectional study was conducted in 151 RA patients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥ 6months: (1) patients with a therapeutic response to DMARDs, with DAS28< 3.2; and (2) patients without a response to DMARDs, with persistent DAS28 ≥ 3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression. Serum P-gp levels were significantly higher in RA patients (n = 151) than in the controls (n = 30) (158.70 ± 182.71ng/mL vs. 14.12 ± 8.97ng/mL, p < 0.001). The P-gp level was correlated with the DAS28 score (r = 0.39, p < 0.001). RA patients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206 ± 21.47ng/mL vs 120.60 ± 15.70ng/mL; p = 0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p = 0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01). Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses.

Baricitinib for Previously Treated Moderate or Severe Rheumatoid Arthritis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal process, the National Institute for Health and Care Excellence invited the manufacturer (Eli Lilly) of baricitinib (BARI; Olumiant®; a Janus kinase inhibitor that is taken orally) to submit evidence of its clinical and cost effectiveness for the treatment of moderate to severe rheumatoid arthritis (RA) after the failure of disease-modifying antirheumatic drugs (DMARDs). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company’s submission (CS) to NICE. The clinical-effectiveness evidence in the CS for BARI was based predominantly on three randomised controlled trials comparing the efficacy of BARI against adalimumab or placebo, as well as one long-term extension study. The clinical-effectiveness review identified no head-to-head evidence on the efficacy of BARI against all the comparators within the scope. Therefore, the company performed network meta-analyses (NMAs) in two different populations: one in patients who had experienced an inadequate response to conventional DMARDs (cDMARD-IR), and the other in patients who had experienced an inadequate response to tumour necrosis factor inhibitors (TNFi-IR). The company’s NMAs concluded BARI had comparable efficacy as the majority of its comparators in both populations. The company submitted a de novo discrete event simulation model that analysed the incremental cost-effectiveness of BARI versus its comparators for the treatment of RA from the perspective of the National Health Service (NHS) in four different populations: (1) cDMARD-IR patients with moderate RA, defined as a 28-Joint Disease Activity Score (DAS28) > 3.2 and no more than 5.1; (2) cDMARD-IR patients with severe RA (defined as a DAS28 > 5.1); (3) TNFi-IR patients with severe RA for whom rituximab (RTX) was eligible; and (4) TNFi-IR patients with severe RA for whom RTX in combination with methotrexate (MTX) is contraindicated or not tolerated. In the cDMARD-IR population with moderate RA, the deterministic incremental cost-effectiveness ratio (ICER) for BARI in combination with MTX compared with intensive cDMARDs was estimated to be £37,420 per quality-adjusted life-year (QALY) gained. In the cDMARD-IR population with severe RA, BARI in combination with MTX dominated all comparators except for certolizumab pegol (CTZ) in combination with MTX, with the ICER of CTZ in combination with MTX compared with BARI in combination with MTX estimated to be £18,400 per QALY gained. In the TNFi-IR population with severe RA, when RTX in combination with MTX was an option, BARI in combination with MTX was dominated by RTX in combination with MTX. In the TNFi-IR population with severe RA for whom RTX in combination with MTX is contraindicated or not tolerated, BARI in combination with MTX dominated golimumab in combination with MTX and was less effective and less expensive than the remaining comparators. Following a critique of the model, the ERG undertook exploratory analyses after applying corrections to the methods used in the NMAs and two programming errors in the economic model that affected the company’s probabilistic sensitivity analysis (PSA) results. The ERG’s NMA results were broadly comparable with the company’s results. The programming error that affected the PSA of the severe cDMARD-IR population had only a minimal impact on the results, while the error affecting the severe TNFi-IR RTX-ineligible population resulted in markedly higher costs and QALYs gained for the affected comparators but did not substantially modify the conclusions of the analysis. The NICE Appraisal Committee concluded that BARI in combination with MTX or as monotherapy is a cost-effective use of NHS resources in patients with severe RA, except in TNFi-IR patients who are RTX-eligible.

JAK inhibitors: A broadening approach in rheumatoid arthritis.

Pfizer's Xeljanz (tofacitinib citrate) was the first Janus kinase (JAK) inhibitor to reach the market for rheumatoid arthritis (RA) following its U.S. approval in November 2012, and it has since gained approval in more than 45 countries as a second-line therapy for RA after failure of disease-modifying antirheumatic drugs (DMARDs). This emerging category has heralded an attractive new class of oral treatment options in RA, with a notable opportunity in patients who stop responding to DMARDs, but they are facing a challenging market. Despite RA affecting approximately 23.7 million people worldwide, Xeljanz faces a market dominated by the anti-tumor necrosis factor (anti-TNF) biologicals, which have robust long-term safety and efficacy. The availability of biosimilars of these market leaders is also intensifying competition, and a high price and uncertainty over long-term safety is currently tempering the market for the JAK inhibitors.

Concomitant methotrexate and tacrolimus augment the clinical response to abatacept in patients with rheumatoid arthritis with a prior history of biological DMARD use.

This observational retrospective study examined whether abatacept efficacy could be augmented with concomitant methotrexate (MTX) or tacrolimus (TAC) in patients with rheumatoid arthritis (RA) who experienced failure with prior biological disease-modifying antirheumatic drugs (DMARDs) and in whom favorable therapeutic efficacy is difficult to achieve. All patients with a prior biological DMARD history who were treated with abatacept for 52weeks and registered in a Japanese multicentre registry were included. Clinical efficacy and safety of abatacept according to the concomitant drug used, i.e., none (ABT-mono), MTX (ABT-MTX), and TAC (ABT-TAC), were compared. A greater mean percent change of DAS28-ESR was observed in the ABT-TAC group compared with the ABT-mono group at weeks 12 (-20.5 vs. -5.4%, p=0.035) and 24 (-25.0 vs. -11.0%, p=0.036). ABT-MTX and ABT-TAC groups had a significantly higher proportion of patients who achieved low disease activity (LDA) within 52weeks compared with the respective baselines, while no significant change was observed in the ABT-mono group. A higher proportion of patients in the ABT-TAC group achieved EULAR moderate response compared with the ABT-mono group at week 52 (66.7 vs. 35.0%, p=0.025). Multivariate logistic regression analysis revealed that concomitant TAC use was independently associated with the achievement of LDA and EULAR response at 52weeks, while concomitant MTX use was not. Concomitant TAC use may offer a suitable option for RA patients treated with abatacept after prior biological DMARD failure, likely because both abatacept and TAC affect T cell activation.

PMS54 - Cost Effectiveness of Tofacitinib as Second Line Treatment vs Using Biological Therapies In The Treatment of Moderate Rheumatoid arthritis after Failure of dmards In Panama In 2014

Rheumatoid Arthritis (RA) affects approximately 0.4% of the Latin American population over 16 years old. [1]. Many patients with rheumatoid arthritis (RA) do not respond adequately with disease-modifying antirheumatic drugs (DMARDs), being eligible for biological treatment available. The objective was to evaluate the cost-effectiveness of Tofacitinib as second line vs continue using biological therapies in moderate RA after failure of DMARDs in Panama’s Ministry of Health (MINSA) in 2014. The cost-effectiveness model uses a patient-level simulation approach and assesses the economic and health benefits for the management of patients with RA who have an inadequate response to methotrexate. The model compares a treatment sequence with Tofacitinib followed by biologic treatments vs a sequence of biological treatments only, in the patient care pathway. The sequence of biologics treatments used in both cases is: Infliximab, Adalimumab, Tocilizumab, Rituximab, Etanercept and salvage therapy, according to experts opinion from MINSA [2]. All patients received concomitant treatment with methotrexate. The characteristics included in model are: age, weight, initial HAQ score, severe adverse events (SAE) and clinical response to short and long term treatment; randomized controlled trials were used as source information when local information was not available [3,4]. HAQ scores were used to calculate utilities, measured in QALYs [5,6,7]. Only direct costs were considerate from MINSA databases of 2014 [8]. A lifetime horizon time was used with an annual discount rate of 5%. Total cost and total QALY per patient in a lifetime period are $193,971 and 9.28 QALY for treatment sequence with Tofacitinib; $205,015 and 9.20 for treatment sequence with biologic therapy. The cost saving for treatment sequence with Tofacitinib in years one, five and ten were: 12%, 10%, 8% respectively. In case of MINSA, the sequence initiating with Tofacitinib is a cost-saving alternative compared with biologic therapy.

PMS58 - Cost Effectiveness of Tofacitinib as Second Line Treatment Vs Using Biological Therapies In The Treatment of Moderate Rheumatoid Arthritis After Failure of Dmards In Guatemala In 2014

Rheumatoid arthritis (RA) is a common autoimmune disease associated with considerable morbidity rates and diminished quality of life. For patients who have an inadequate response to disease-modifying antirheumatic drugs (DMARDs), the use of biologic agents and JAK inhibitor has proved to be effective as second-line treatment. [1]. To evaluate the cost-effectiveness of Tofacitinib as second line treatment vs using the standard biological therapies as second line treatments in patients with moderate RA after failure of DMARDs in Guatemala Health Care System (IGSS) in 2014. A patient-level simulation model was used to evaluate costs and health benefits. This cost-effectiveness model compares two sequences of treatments: one using Tofacitinib as second line treatment followed by biological therapies (Tofacitinib-Infliximab-Adalimumab-Etanercept-Tocilizumab-Rituximab-salvage therapy ) and the other using the same biologic therapies scheme but excluding Tofacitinib; these schemes are defined according to experts opinion from IGSS [2]. All patients received concomitant treatment with methotrexate. Model inputs are: age, weight, initial HAQ score, severe adverse events (SAE) and clinical response to short and long term treatment; randomized controlled trials were used as a source information when local information was not available [3,4]. HAQ scores were used to calculate utilities, measured in QALYs [5,6,7]. Only direct costs were considered using institutional databases from 2014. [8]. Annual discount rate was 5%, the time horizon is to lifetime. Total cost and total QALY per patient in a lifetime period are estimated to be $213,009 and 8.83 QALY for the treatment sequence with Tofacitinib; $222,145 and 8.52 for treatment sequence with biologic therapy only. The cost savings from the treatment sequence with Tofacitinib are 15.2% in the first year, 15.0% in 5 year and 10.7% in ten years. For the IGSS, the sequence initiating with Tofacitinib is a cost-saving alternative compared with the standard biologic therapy

A Single Center Experience in Biological Therapy for the Treatment of Rheumatoid Arthritis in Saudi Arabia

Background: Biological therapy is indicated in the treatment of RA (Rheumatoid Arthritis) after failure of disease-modifying anti-rheumatic drugs (DMARDS) by the ACR/EULAR recommendations. The objective of the study is to describe the characteristics of Saudi patients at the initiation of biological therapy and to evaluate clinical effectiveness of this therapy measured by the disease activity score DAS 28. Methods: This was a retrospective cohort study of RA (rheumatoid arthritis) patients in King Fahad Hospital in Jeddah, Saudi Arabia from January 2005-July 2011. Data were collected from the medical records of all RA patients on biological therapy including: demographics, disease characteristics, comorbid illnesses and DAS 28 score over a period of 1 year. Results: 139 patients were studied (mean age 46 ± 13 years), of which 118 (84%) were females; mean duration of affliction with RA was 7.2 years ranging 1-45 years. Rheumatoid factor (RF) was positive in 88 patients (63.3%) and one or more comorbidities were present in 102 patients (73.3%). First choice of biological drug was ADA (Adalimumab) 44 patients (31.7%) and RTX (Rituximab) was the 2nd frequently prescribed biological drug. Mean DAS 28 activity at baseline was in ADA 41 patients (6.10 ± 1.62), ETA (Etarnercept) 29 patients (6.64 ± 1.42) and RTX 50 patients (6.7 ± 1.32). Moderate to good EULAR response was obtained in 74%, 85.7% and 53.3% at 6 months in ADA, ETA and RTX patients respectively. Moderate to good EULAR response was obtained in 61.8%, 86.6% and 72% in ADA, ETA AND RTX patients respectively at 1 year of treatment. Therapeutic effectiveness was comparable with the response rates in published observational trials. Conclusion: Our data demonstrate daily clinical practice in management of RA. The pattern of prescription is in agreement with the ACR/EULAR recommendations for initiation of biologicals in the treatment of RA.

Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use

BackgroundThe effects of fish oil (FO) in rheumatoid arthritis (RA) have not been examined in the context of contemporary treatment of early RA. This study examined the effects of high...

Golimumab for the Treatment of Rheumatoid Arthritis After the Failure of Previous Disease-Modifying Antirheumatic Drugs: A NICE Single Technology Appraisal

As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of golimumab (Simponi(®); Merck Sharp & Dohme, USA) was invited to submit evidence for its clinical and cost effectiveness for the treatment of rheumatoid arthritis (RA) after the failure of previous disease-modifying antirheumatic drugs (DMARDs). The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at The University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). This article provides details of the manufacturer's initial submission, the ERG's clarification questions and the ERG report submitted to NICE. The decision made by NICE is provided alongside a brief comment on additional results produced from an additional analysis requested by NICE on behalf of the Committee. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based on upon the manufacturer's submission to NICE. The clinical evidence was derived from three randomized controlled trials of golimumab in the treatment of moderate to severe RA: GO-FORWARD and Kay et al. (DMARD-experienced population) and GO-AFTER (tumour necrosis factor [TNF]-α inhibitor-experienced population). The ERG considered that the trials were of reasonable methodological quality and measured a clinically relevant range of outcomes. The trials for golimumab, as well as comparator treatments, were synthesized using mixed-treatment comparison methods for the DMARD-experienced population and an indirect comparison using the Bucher method for the TNF-α inhibitor-experienced population. The trials used were appropriate, although no definitive judgement regarding the comparative efficacy of golimumab with other biologics was possible. The manufacturer provided a DMARD-experienced population model and a TNF-α inhibitor-experienced population model. The models allowed sequences of treatments to be evaluated for each population, although a fully incremental analysis between the use of golimumab following DMARD failure and the use of golimumab following TNF-α inhibitor failure was not possible. Several limitations with the model were identified, and after a request from NICE and suspension of the appraisal, the manufacturer submitted sensitivity analyses with an additional American College of Rheumatology 70 % improvement criteria (ACR70) health state included, using SF-36 data directly from the GO-FORWARD study. The annual rate of the Health Assessment Questionnaire (HAQ) score increase for patients receiving palliative treatment was also changed from 0.09 to 0.06. The further analyses provided highlighted the particular sensitivity of the results to HAQ progression rates and the re-administration frequency for rituximab in the TNF-α inhibitor-experienced population. The Appraisal Committee concluded that golimumab should be recommended in combination with methotrexate as an option for patients with severe active RA who have failed on conventional DMARDs, or who have failed on a TNF-α inhibitor and are contraindicated to or withdrawn from rituximab.

Clinical Pharmacogenetic Model to Predict Response of MTX Monotherapy in Patients with Established Rheumatoid Arthritis After DMARD Failure

The performance of a clinical pharmacogenetic model to predict nonresponse of methotrexate (MTX) monotherapy in patients with established rheumatoid arthritis (RA) and failure of disease-modifying antirheumatic drugs (DMARDs) was studied. For 75 RA patients receiving MTX monotherapy for 6 months, DNA and clinical data were available. Risk scores for nonresponse at 6 months (disease activity score >2.4), were calculated using the pharmacogenetic prediction model utilizing four clinical factors and four polymorphisms in the genes MTHFD1, AMPD1, ITPA and ATIC. At 6 months, there were 25 responders and 50 nonresponders. Using the clinical pharmacogenetic prediction model, 75% (56 out of 75) were categorized into predicted responders (risk score ≤ 3.5) and predicted nonresponders (risk score ≥ 6). At 6 months, the negative predictive value was 81% (21 out of 26) and the positive predictive value was 47% (14 out of 30). The pharmacogenetic model predicts nonresponse to MTX monotherapy, but performs better in DMARD naive recent-onset RA patients than in patients with preceding DMARD failure.

Rheumatoide Arthritis - Meilensteine für Klassifikation und Therapie

New classification criteria of rheumatoid arthritis (RA) by the American College of Rheumatology and the European League Against Rheumatism (EULAR) allow the early assignment of arthritides as RA and thus early start of therapy. This is an important step towards early diagnosis and treatment. The EULAR recommendations for the treatment of RA for the first time define the value of biologicals by means of therapeutic algorithms based on extensive scientific evidence and taking into account cost-effectiveness. As a result biologicals can be used after the first failure of disease-modifying anti-rheumatic drugs (DMARDs), if there are unfavourable prognostic factors. Methotrexate is, as a DMARD, at the centre of treatment.

Update on the treatment of peripheral arthritis in psoriatic arthritis

Psoriatic arthritis is a chronic, disabling disease for which therapies have been borrowed from rheumatoid arthritis and spondylitis. Traditional disease-modifying antirheumatic drugs (DMARDs) remain the first choice for the treatment of peripheral arthritis despite scarce evidence of their efficacy or ability to halt radiographic progression. Tumor necrosis factor antagonists have the greatest level of evidence for symptom control and radiographic progression. They are currently used after the failure of DMARDs to effectively treat peripheral arthritis, enthesitis, and dactylitis, and are the first choice when axial disease predominates. Despite the use of these treatments, 30% to 40% of patients will still have active disease. Among new drugs, evidence of efficacy has already been published with regard to anti-IL12/23 monoclonal antibody (ustekimumab) and golimumab. Results are forthcoming from trials with certolizumab pegol, abatacept, and rituximab. As knowledge of the pathogenesis of psoriatic arthritis evolves and differences among other arthritis conditions become evident, therapies targeting these distinct features are needed.

Quality appraisal of clinical practice guidelines and consensus statements on the use of biologic agents in rheumatoid arthritis: A systematic review

To evaluate the quality of clinical practice guidelines (CPGs) and consensus statements (CS) for the treatment of rheumatoid arthritis with tumor necrosis factor alpha (TNFalpha) antagonists. We searched for CPGs and CS on the use of infliximab, etanercept, and/or adalimumab for the treatment of rheumatoid arthritis, published through October 10, 2006. Sources included electronic databases (Medline, EMBase, BIOSIS, etc.), guideline registries, and pertinent Web sites. Review of 4,915 citations revealed 16 CPGs and 20 CS. Two independent reviewers evaluated development methods of selected studies using the 23-item Appraisal of Guidelines for Research and Evaluation (AGREE) instrument and compared recommendations between guidelines. Of the 16 guidelines, only 5 (31%) were based on a systematic review of relevant research evidence. Only 4 (25%) of the guidelines fulfilled > or = 60% of the AGREE criteria. AGREE scores were lower for guidelines from rheumatology societies than government agencies when reporting scope and purposes (P = 0.03), stakeholder involvement (P = 0.03), and clarity and presentation (P = 0.01). Guidelines scored higher than CS in most domains. Overall, guideline recommendations were consistent with respect to the use of biologic agents after failure of disease-modifying antirheumatic drugs, but differed or did not provide specific guidance on tests for screening. Guidelines for introducing TNFalpha antagonists in rheumatoid arthritis often fail to meet expected methodologic criteria and therefore vary significantly in quality and with respect to some recommendations for patient assessment and management.

Review of eight pharmacoeconomic studies of the value of biologic DMARDs (adalimumab, etanercept, and infliximab) in the management of rheumatoid arthritis.

Treatment options for the management of rheumatoid arthritis (RA) have expanded from the traditional disease-modifying antirheumatic drugs (DMARDs) to include the biologic DMARDs that inhibit tumor necrosis factoralpha (TNF-a). To assess the medical literature for studies of the economic value of biologic DMARDs, specifically the 3 TNF-a inhibitors (adalimumab, etanercept, and infliximab) used for the management of RA, compared with the traditional DMARDs such as sulfasalazine, antimalarials, penicillamine, gold, methotrexate, azathioprine, leflunomide, and cyclophosphamide. A comprehensive search of the MEDLINE and HealthSTAR databases was conducted to identify cost-efficacy, cost-effectiveness, or cost-utility studies published in the English language (from 1966 through November 2004). The search terms and/or MeSH (medical subject headings) titles were cost-benefit analysis, rheumatoid arthritis, antirheumatic agents, antineoplastic and immunosuppressive agents. Studies were critically reviewed and quality was assessed using the Quality of Health Economic Studies instrument. Most studies evaluated the use of biologics among RA patients resistant to DMARDs. Studies were assessed with regard to comparators evaluated, measures of efficacy, perspectives, model duration, treatment duration, and discount rate. From 180 titles identified, 155 were excluded for the following reasons: 89 because they did not consider the drugs of interest, 15 because the population was not RA, 19 because of having the wrong drugs and population, 22 because they were review articles, and 10 because they were general articles. Twentyfive abstracts were accepted for further review. Of these, 13 abstracts were subsequently selected for full-text review. One of the authors identified a study not indexed in MEDLINE. Ultimately, 2 cost-effectiveness and 6 cost-utility studies were selected for this critical review. One study over 6 months reported that triple therapy with DMARDs (methotrexate-hydroxychloroquine-sulfasalazine) was cost effective for methotrexate-resistant patients, which is consistent with American College of Rheumatology (ACR) guidelines that support the use of triple therapy prior to biologics. The incremental cost-effectiveness ratio (ICER) was $1,500 per patient to achieve an ACR20 response for this triple therapy compared with no second-line agent. Overall, biologic therapies cost considerably more than traditional DMARDs but produced more quality-adjusted life-years (QALYs). Despite differences in design and assumptions, published economic models consistently reported ICERs <50,000 dollars per QALY gained for biologics compared with traditional DMARDs, although ICERs of >100,000 dollars were reported from sensitivity analyses. Clinical guidelines currently recommend the use of biologics as step therapy after failure of traditional DMARDs. Reported ICERs comparing biologics with traditional DMARDs are within a range that is comparable with other accepted medical interventions. The worth of the additional expenditure will ultimately be judged by formulary and policy decision makers because no maximum cost has been defined. Models can be used to inform decision makers, but they must be interpreted and applied carefully. More research is also needed to differentiate the relative economic value of the various biologic agents by therapeutic indication.