The comparative effectiveness of tumor necrosis factor-blocking agents in patients with rheumatoid arthritis and patients with ankylosing spondylitis: a six-month, longitudinal, observational, multicenter study

OBJECTIVE: To compare the effectiveness of tumor necrosis factor (TNF)-blocking agents (etanercept and infliximab) in patients with rheumatoid arthritis (RA) and patients with ankylosing spondylitis (AS). METHODS: Data from an ongoing longitudinal, observational study in Norway were used to assess changes in health-related quality of life (HRQOL) in patients with RA (n = 291) and AS (n = 62). Patients received anti-TNF therapy, and changes in scores on the Short Form 36 (SF-36), SF-6D, modified Health Assessment Questionnaire, and visual analog scales for patients' assessments of pain, fatigue, and global status from baseline to followup examinations at 3 and 6 months were compared. Data were adjusted for age, sex, and baseline values and are presented as crude estimates as well as standardized response means. RESULTS: Both groups had improvements in all measures at 3 and 6 months. At 3 months, the changes were significantly better in the AS group compared with the RA group for all measures except the SF-36 social functioning scores. At 6 months, all changes were numerically greater in the AS group. Differences were significant for the SF-36 role emotional scores and were borderline significant for the SF-36 physical functioning, role physical, and vitality scores and for the SF-6D scores. CONCLUSION: In this real-life setting, patients with AS experienced improvement in HRQOL that was comparable to, and sometimes greater than, that observed in RA patients. These results support the idea that patients with AS should have the same access to TNF-blocking agents as patients with RA.     

The comparative one‐year performance of anti–tumor necrosis factor α drugs in patients with rheumatoid arthritis,psoriatic arthritis,and ankylosing spondylitis: Results from a longitudinal,observational, multicenter study

Objective

To compare the 1‐year retention rates of anti–tumor necrosis factor α (anti‐TNFα) medications in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) with complementary analyses of the effect on health status.

Methods

Our analyses comprised 847, 172, and 249 anti‐TNFα treatment courses in patients with RA, PsA, and AS, respectively. Crude drug survival was compared and hazard ratios (HRs) for treatment termination were calculated with adjustments for age, sex, investigator's global assessment, and concomitant methotrexate (MTX). Adjusted changes in health‐related quality of life (HRQOL) were compared among the groups.

Results

Unadjusted 1‐year retention rates were 65.4%, 77.3%, and 77.5% in the RA, PsA, and AS groups, respectively. The adjusted HRs for treatment termination were 0.76 (95% confidence interval [95% CI] 0.53–1.07) for PsA versus RA and 0.66 (95% CI 0.47–0.92) for AS versus RA. High baseline disease activity and female sex were significantly associated with premature treatment termination, whereas concomitant MTX was associated with better drug survival. However, the impact of MTX was apparent for RA and PsA, but not for AS in stratified analyses. The improvements in HRQOL were superior in patients with PsA and AS compared with RA.

Conclusion

Our results suggest that survival of anti‐TNFα treatment is superior in AS and PsA patients compared with RA patients. Larger improvements in HRQOL in patients with spondylarthritides may contribute to the differences in drug survival. Concomitant MTX was associated with better retention rates in RA and PsA patients, but not AS patients.     

The comparative one-year performance of anti-tumor necrosis factor alpha drugs in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: results from a longitudinal, observational, multicenter study

OBJECTIVE: To compare the 1-year retention rates of anti-tumor necrosis factor alpha (anti-TNFalpha) medications in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) with complementary analyses of the effect on health status. METHODS: Our analyses comprised 847, 172, and 249 anti-TNFalpha treatment courses in patients with RA, PsA, and AS, respectively. Crude drug survival was compared and hazard ratios (HRs) for treatment termination were calculated with adjustments for age, sex, investigator's global assessment, and concomitant methotrexate (MTX). Adjusted changes in health-related quality of life (HRQOL) were compared among the groups. RESULTS: Unadjusted 1-year retention rates were 65.4%, 77.3%, and 77.5% in the RA, PsA, and AS groups, respectively. The adjusted HRs for treatment termination were 0.76 (95% confidence interval [95% CI] 0.53-1.07) for PsA versus RA and 0.66 (95% CI 0.47-0.92) for AS versus RA. High baseline disease activity and female sex were significantly associated with premature treatment termination, whereas concomitant MTX was associated with better drug survival. However, the impact of MTX was apparent for RA and PsA, but not for AS in stratified analyses. The improvements in HRQOL were superior in patients with PsA and AS compared with RA. CONCLUSION: Our results suggest that survival of anti-TNFalpha treatment is superior in AS and PsA patients compared with RA patients. Larger improvements in HRQOL in patients with spondylarthritides may contribute to the differences in drug survival. Concomitant MTX was associated with better retention rates in RA and PsA patients, but not AS patients.     

Modeling the 5‐year cost effectiveness of treatment strategies including tumor necrosis factor‐blocking agents and leflunomide for treating rheumatoid arthritis in the Netherlands

Objective

To determine the cost effectiveness of treatment strategies for rheumatoid arthritis patients satisfying the indication for tumor necrosis factor (TNF)‐blocking treatment.

Methods

A Markov model study was performed. The following treatment strategies were considered: 1) usual treatment; 2) treatment with leflunomide, in the case of nonresponse after 3 months, switch to usual treatment; 3) TNF‐blocking treatment, in the case of nonresponse after 3 months, switch to usual treatment; 4) treatment with leflunomide, in the case of nonresponse, switch to TNF‐blocking treatment, in the case of nonresponse to TNF‐blocking treatment, switch to usual treatment; 5) TNF‐blocking treatment, in the case of nonresponse, switch to leflunomide treatment, in the case of nonresponse to leflunomide, switch to usual treatment. Expected patient‐years in the different Markov states, costs, and quality‐adjusted life years (QALYs) were compared between the treatment strategies; incremental cost‐effectiveness ratios (ICERs) were calculated.

Results

Over the 5‐year period, the expected effect on disease activity and QALYs was better for treatment strategies that included TNF‐blocking treatment than for the other treatment strategies. The greater effectiveness of these treatment strategies reduced medical and nonmedical costs compared with usual treatment by about 16% and 33%, respectively, omitting the costs of medication. When the costs of medication were included, the costs of strategies that started with TNF‐blocking treatment were higher than those of the other treatment strategies. Treatment strategy 4 had the most favorable ICER of the treatment strategies that included TNF‐blocking treatment: €163,556/QALY compared with usual treatment.

Conclusion

Among strategies that include TNF‐blocking agents, one starting with leflunomide and, in the case of nonresponse, switching to TNF‐blocking treatment probably results in the most favorable ratio between incremental costs and effects.

     

肿瘤坏死因子拮抗剂治疗类风湿关节炎和强直性脊柱炎发生结核的风险

目的了解类风湿关节炎(RA)和强直性脊柱炎(AS)患者在应用肿瘤坏死因子(TNF)拮抗剂治疗前后结核病的发病风险。方法随访2003年7月至2006年2月期间进行英利昔单抗和依那西普临床试验的RA和AS患者,筛选时对所有患者均进行结核菌素纯蛋白衍生物(PPD)皮试及拍摄胸部正侧位X线片．随访过程中密切观察结核的发生情况。结果筛选的67例RA患者中1例PPD阳生,英利昔单抗治疗结束后发生右锁骨上淋巴结结核1例；203例AS筛选患者中27例PPD阳性,2例胸部X线片发现肺部结核钙化灶．2例为肺部结核,入选AS患者试验期间及随访过程中均无结核病发生。临床试验筛选的RA和AS患者的PPD阳性及胸片显示结核活动或有钙化灶的统计数据显示均低于我国全人口的结核感染率和活动性肺结核患病率。其差异有统计学意义(P＜0．01)。结论本研究未发现RA和AS患者接受抗TNF治疗前后结核发病的风险的增高,但在应用TNF拮抗剂治疗前,建议应严格掌握适应证,避免严重不良反应的发生。     

The comparative effectiveness of anti-TNF therapy and methotrexate in patients with psoriatic arthritis: 6 month results from a longitudinal, observational, multicentre study

OBJECTIVES: To compare the response to treatment with tumour necrosis factor (TNF) inhibitors and methotrexate (MTX) monotherapy in patients with psoriatic arthritis (PsA) within a real-life clinical setting. METHODS: We analysed data from an ongoing longitudinal, observational multicentre study in Norway. Our data comprised 526 cases of patients with PsA who received either anti-TNF treatment (n = 146) or MTX monotherapy (n = 380) and were followed for at least 6 months with measures of disease activity, health status and utility scores. A propensity score was computed to adjust for channelling bias. The changes in measures of disease activity and health-related quality of life from baseline to 3- and 6-month follow-up were compared between the groups with adjustments for the baseline value of the dependent variable and the propensity score (analyses of covariance (ANCOVA)). RESULTS: The groups were significantly different at baseline with respect to demographic and disease activity measures. The variables included in the propensity score were age, sex, number of previous disease modifying anti-rheumatic drugs (DMARDs), presence of erosive disease, treatment centre and investigator's global assessment. The adjusted changes at 6 months were significantly larger in the anti-TNF group for ESR, DAS-28, M-HAQ, patient's assessments of pain, fatigue and global disease activity on a visual analogue scale (VAS) and 4 out of 8 SF-36 dimensions. CONCLUSIONS: Clinical improvement was superior with TNF inhibitors compared to MTX monotherapy in patients with PsA, when assessed in this setting of daily clinical practice.     

Role of tumor necrosis factor‐alpha in rheumatoid arthritis: a review

Tumor necrosis factor‐alpha (TNF‐α) is a proinflammatory cytokine that plays a pivotal role in regulating the inflammatory response in rheumatoid arthritis (RA). Although it is controversial whether TNF‐α genes are associated with RA susceptibility, they are well known to mediate RA pathogenesis. We review in depth the history, formation and biological action, TNF receptor, role in mediating pathogenesis in RA and mode of action, of anti‐TNF‐α drugs.     

A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients

In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy—based on creatinine level, proteinuria and disease activity—was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.     

The effect of tumor necrosis factor blockade on the response to pneumococcal vaccination in patients with rheumatoid arthritis and ankylosing spondylitis

OBJECTIVE: To assess the effect of anti-tumor necrosis factor (TNF) alpha therapies on the immunogenicity of pneumococcal vaccination in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: A group of 16 consecutive patients (11 with RA and 5 with AS) treated either with infliximab or etanercept, and a control group of 17 age-matched RA patients treated with disease-modifying medications other than anti-TNF-alpha, received intradeltoid injection with 0.5 mL of pneumococcal vaccine. Pneumococcal polysaccharide (PPS)-specific IgG to 7 vaccine PPS (representing high- and low-prevalence serotypes) was measured by enzyme-linked immunosorbent assay in sera obtained before and 1 month after pneumococcal immunization. RESULTS: One month after vaccination, both groups had significant increases in the geometric mean concentration of capsule PPS-specific antibody and in the mean fold increase in antibody levels to all 7 serotypes, compared with prevaccination levels. However, compared with the control group, the TNF-alpha blockade-treated patients tended to have lower antibody increases for all the serotypes tested except serotype 14. In addition, lower proportions of TNF-alpha blockade-treated patients responded to pneumococcal vaccination compared with patients on other therapies. Similarly, more TNF-alpha blockade-treated patients were poor responders compared with patients not on anti-TNF-alpha treatment. CONCLUSION: Treatment of groups of patients with etanercept or infliximab does not impair their mean antibody responses to pneumococcal vaccination. However, a larger proportion of RA patients may not respond adequately to pneumococcal vaccination once on TNF-alpha blockade therapies. Consequently, pneumococcal vaccination before starting TNF-alpha blockade therapy is recommended.     

Risk of tuberculosis in a Chinese registry of rheumatoid arthritis and ankylosing spondylitis for tumour necrosis factor‐α antagonists

Aim: To understand the risk of tuberculosis (TB) infection in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) who required tumour necrosis factor‐α (TNF‐α) antagonist treatment. Methods: Patients with RA and AS who were screened for infliximab and etanercept treatment for up to 6 months were entered in a registry between 2003 and 2005. The purified protein derivative (PPD) test and chest anteroposterior and lateral view X‐ray were performed at screening. The risk of TB infection in theses patients was observed during follow up. Results: Among 67 RA patients screened, a positive PPD reaction was found in one patient. Of the 169 AS patients screened, 23 were positive for the PPD reaction, two had pulmonary TB calcinosis and two were diagnosed as having pulmonary TB. The incidence of PPD positive reaction and pulmonary TB calcinosis or active TB in our screened RA and AS patients was significantly lower than that reported in the recent fourth national TB infection rates and prevalence (P < 0.01). Only one patient with RA developed neck lymph node TB 6 months after completion of infliximab infusion. Conclusion: Patients with AS and RA are not at an increased risk of TB infection if screened properly before short course treatment with anti‐TNF‐α agents.     

B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: A six‐month,national, multicenter,open‐label study

Objective

To examine whether serum B cell markers can predict response to rituximab, a B cell–depleting monoclonal antibody, in patients with refractory rheumatoid arthritis (RA).

Methods

This rituximab re‐treatment dose study (SMART [eSsai MAbthera sur la dose de Re‐Traitement]) involved 208 patients with refractory RA. Serum markers of B cell activation (anti–cyclic citrullinated peptide [anti‐CCP] antibodies, rheumatoid factor [RF], serum IgG, IgA, and IgM levels, serum κ and λ free light chains, and serum BAFF) were assessed before the first rituximab cycle (1,000 mg on days 1 and 15). Univariate and multivariate analyses were performed to identify factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks.

Results

There were 149 responders (72%). Two baseline factors were associated with a EULAR response at 24 weeks in multivariate analysis: the presence of anti‐CCP antibodies or RF (odds ratio 3.5 [95% confidence interval 1.6–7.6]) and a serum IgG concentration above normal (odds ratio 2.11 [95% confidence interval 1.02–4.33]), with synergy between them (odds ratio 6.0 [95% confidence interval 2.2–16.2]).

Conclusion

The presence of RF or anti‐CCP antibodies and elevated IgG are 2 simple biomarkers that can be used routinely before therapy to predict response to rituximab in patients with refractory RA.

     

Tumor necrosis factor–inhibiting therapy preferentially targets bone destruction but not synovial inflammation in a tumor necrosis factor–driven model of rheumatoid arthritis

Objective

To investigate how tumor necrosis factor (TNF)–inhibiting therapy affects bone destruction and inflammation in a TNF‐driven mouse model of rheumatoid arthritis.

Methods

In order to evaluate the influence of TNF on osteoclastogenesis in vitro, different concentrations of TNF were added to spleen cell–derived monocytes in the absence or presence of different concentrations of RANKL. In addition, the effects of TNF inhibition on osteoclast precursors as well as local bone destruction in vivo were assessed by treating TNF‐transgenic mice with different doses of adalimumab.

Results

TNF stimulated osteoclastogenesis mainly by increasing the number of osteoclast precursor cells in vitro. This TNF effect was independent of the presence of RANKL. In the hTNF‐transgenic mouse model of destructive arthritis, low‐dose TNF‐inhibiting therapy with adalimumab had no effect on synovial inflammation but significantly inhibited local bone destruction and the generation of osteoclasts. This inhibition was accompanied by a reduction in the number of c‐Fms–positive osteoclast precursor cells in the bone marrow and a reduction of the osteoclast precursor pools in the blood and inflamed synovial membrane of hTNF‐transgenic mice.

Conclusion

Low‐dose TNF‐inhibiting therapy significantly reduces bone erosions by reducing the number of circulating and joint‐invading osteoclast precursors. This effect is uncoupled from its antiinflammatory action.

     

Efficacy of tacrolimus in rheumatoid arthritis patients who have been treated unsuccessfully with methotrexate: A six‐month,double‐blind,randomized, dose‐ranging study

Objective

To assess the efficacy, safety, and optimal dose of tacrolimus monotherapy in patients with rheumatoid arthritis (RA).

Methods

This phase II, randomized, double‐blind, placebo‐controlled monotherapy study was set in 12 community sites and 9 university‐based sites. Two hundred sixty‐eight patients with RA who were resistant to or intolerant of methotrexate (mean dose 15.2 mg/week) and had active disease for at least 6 months (mean tender joint count 28.2, mean erythrocyte sedimentation rate 46.5 mm/hour) were randomized to receive treatment after discontinuation of methotrexate. Those who received at least 1 dose of tacrolimus were analyzed; 141 completed the study. Stable dosages of nonsteroidal antiinflammatory drugs and low‐dose prednisone were allowed during treatment. All patients were given 1, 3, or 5 mg of tacrolimus or placebo once daily for 24 weeks. The American College of Rheumatology definition of 20% improvement (ACR20) and the tender and swollen joint counts at the end of treatment were the primary outcomes.

Results

ACR20 response rates demonstrated a clear dose response. The ACR20 response was observed in 15.5% of patients receiving placebo (95% confidence interval [95% CI] 7.1–23.9%), 29% of the 1 mg tacrolimus group (95% CI 18.3–39.7%) (P < 0.058); 34.4% of the 3 mg group (95% CI 22.7–46.0%) (P < 0.013), and 50% of the 5 mg group (95% CI 37.8–62.3%) (P ≤ 0.001). The tender joint count improved statistically significantly in all tacrolimus groups. The swollen joint count, physical function, and patient‐assessed pain improved statistically significantly in the 3 mg and 5 mg groups. The incidence of creatinine elevation ≥40% above baseline levels increased in a dose‐dependent manner. Dropout rates were high (41–59%) and were more common for inefficacy in the placebo patients (71.4%), whereas they were more common for toxicity in the high‐dose tacrolimus groups (31–33%). Discontinuation for creatinine elevation occurred in the 3 mg (3.1%) and 5 mg (10.9%) tacrolimus groups.

Conclusion

Tacrolimus improved disease activity in methotrexate‐resistant or ‐intolerant patients with RA. A dose response was observed when efficacy and toxicity were assessed at different doses. The optimal dose of tacrolimus appears to be >1 mg but ≤3 mg daily.

     

Correlation of magnetic resonance imaging–based knee cartilage T2 measurements and focal knee lesions with body mass index: Thirty‐six–month followup data from a longitudinal,observational multicenter study

Objective

To compare magnetic resonance imaging (MRI)–based knee cartilage T2 measurements and focal knee lesions and 36‐month changes in these parameters among knees of normal controls and knees of normal weight, overweight, and obese subjects with risk factors for knee osteoarthritis (OA).

Methods

A total of 267 subjects ages 45–55 years from the Osteoarthritis Initiative database were analyzed in this study. Two hundred thirty‐one subjects had risk factors for knee OA, but no radiographic OA (Kellgren/Lawrence score ≤1) at baseline. Thirty‐six subjects were normal controls. Subjects with OA risk factors were stratified in 3 groups: normal weight (n = 78), overweight (n = 84), and obese (n = 69). All subjects underwent 3T MRI of the right knee at baseline and after 36 months. Focal knee lesions were assessed and cartilage T2 measurements (mean T2 and T2 texture analysis) were performed.

Results

The baseline prevalence and severity of meniscal and cartilage lesions were highest in obese subjects and lowest in normal controls (P < 0.05). Obese subjects had the highest mean T2 values and the most heterogeneous cartilage (as assessed by T2 texture analysis), while normal controls had the lowest mean T2 values and the most homogeneous cartilage at baseline (P < 0.05). Increased body mass index (BMI) was significantly (P < 0.05) associated with greater progression of cartilage lesions and constantly elevated cartilage T2 entropy over 36 months.

Conclusion

In preclinical OA, increased BMI is associated with more severe cartilage degeneration as assessed by both morphologic and quantitative MRI measurements.     

The effectiveness of anti–tumor necrosis factor therapy in preventing progressive radiographic joint damage in rheumatoid arthritis: A population‐based study

Objective

To compare the effectiveness of 3 therapeutic strategies in preventing progressive joint damage, in a population‐based cohort. The 3 strategies were infliximab with concomitant disease‐modifying antirheumatic drugs (DMARDs), etanercept with concomitant DMARDs, and etanercept alone.

Methods

We used sequential radiographs to assess all patients who were treated with infliximab or etanercept for >10 months. The rates of erosion progression and joint space narrowing (JSN) were analyzed using multivariate regression models for longitudinal data, with adjustment for potential confounders.

Results

A total of 372 patients treated with anti–tumor necrosis factor (TNF) therapies met the inclusion criteria. The baseline characteristics of the patients assigned to the 3 strategies were not significantly different, except that, as expected, more patients were receiving combination therapy with infliximab. The combination of infliximab plus DMARDs was significantly more effective than etanercept alone for controlling erosion progression (P < 0.001), but the effectiveness of the 2 combination‐treatment strategies was similar (P = 0.07). The combination of infliximab plus DMARDs was also more effective at controlling progressive JSN compared with etanercept alone (P = 0.04) or etanercept plus DMARDs (P = 0.02). Treatment with anti‐TNF agents (infliximab or etanercept) plus concomitant DMARDs was more effective than treatment with etanercept alone for controlling erosion progression (P = 0.045).

Conclusion

When combined with traditional DMARDs, both etanercept and infliximab appear to offer similar protection against progressive structural joint damage, and combination therapy with either of these agents appears to be more effective than treatment with etanercept alone.

     

Antigen‐specific immunomodulation of collagen‐induced arthritis with tumor necrosis factor–stimulated dendritic cells

Objective

Dendritic cells (DCs) are crucial for the initiation of T cell immunity and therefore play an important role in the initiation and regulation of immune responses in arthritis. Full mobilization of effector T cells depends on the proper maturation of DCs. Current evidence indicates that the type of T cell response induced is crucially dependent on the activation status of the DCs. In this study, we explored the immunologic effects of differentially matured DCs on the development of collagen‐induced arthritis (CIA).

Methods

Bone marrow–derived DCs were cultured in the presence of granulocyte–macrophage colony‐stimulating factor (GM‐CSF). Before immunization with bovine type II collagen (CII) protein, mice were repeatedly injected with DCs that had been pulsed with CII. Immature, semimature, or fully mature DCs were injected. Mice were boosted on day 21 after CII immunization, and the disease course was monitored.

Results

While vaccination with immature or lipopolysaccharide‐activated DCs had no significant effect on the disease course, administration of antigen‐loaded, tumor necrosis factor (TNF)–modulated DCs propagated in GM‐CSF with or without interleukin‐4 resulted in a delayed onset of arthritis and a lower clinical score. The response was antigen‐specific, since TNF‐treated DCs pulsed with a control antigen did not modify the disease course. A specific decrease in the collagen‐specific “Th1‐associated” IgG2a response was observed, whereas IgG1 titers were unaffected.

Conclusion

CIA can be prevented through vaccination with TNF‐matured DCs in an antigen‐specific manner. These findings provide a rationale for immunotherapy using DCs in rheumatoid arthritis.

     

Current aspects of cost effectiveness of TNF-alpha blocking agents in patients with rheumatoid arthritis

Facing increasing health-related costs and limited health care resources, the assessment of cost effectiveness (CE) of medical procedures is also gaining considerable importance in the field of rheumatology. Since high annual therapy costs of 17,000-21,000 Euro are related to the employment of TNF-alpha blocking agents such as etanercept and infliximab (compared to annual costs of 350-5000 Euro of other disease modifying drugs (DMARDs) in the treatment of rheumatoid arthritis (RA)), their CE has become an important issue. The present investigation summarizes economic evaluations of cost and effectiveness of TNF-alpha blocking agents and compares the results to those of traditional DMARD therapies in patients with RA. The implications of these economic results on the further use of TNF-alpha blocking drugs and methodological improvements of their economic evaluation are discussed. The current literature provides evidence for the CE of the combination therapy with methotrexate (MTX), hydroxychloroquine (HCQ), and sulfasalazine (SASP). In comparison to this finding, the use of etanercept and MTX yields much higher costs, although the highest rate of ACR20 responses is achieved by this combination (additional costs of $42,000 per ACR20 response compared to combination of MTX, HCQ, and SASP). Two recent studies show more promising results of about $12,000/QUALY and even cost savings per QUALY administering etanercept and infliximab, respectively. The wide range of the CE ratios is mainly explained by different methodological approaches. Whether the wider employment of TNF-alpha blocking drugs (comprising not only selected patients) proves to be economically effective, remains to be investigated by further economic analyses. In contrast to the initial disappointing results of the comparison of established DMARD therapies and TNF-alpha blocking drugs in terms of CE, recently published data renders evidence that the CE of the TNF-alpha blocking drugs is comparable to other accepted therapies in internal medicine.