Superior efficacy of combination therapy for rheumatoid arthritis: Fact or fiction?

Smolen, Josef S.; Aletaha, Daniel; Keystone, Edward

doi:10.1002/art.21293

Cited by 76 publications

(47 citation statements)

References 47 publications

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“…Adding etanercept in a step-up approach to sulfasalazine did not seem to offer any clinical advantage over switching to etanercept, which is in agreement with recent studies on combination therapies with other DMARDs. 25 However, in the absence of radiography data, it is not known whether these clinical results would be directly correlated with benefit from radiography. No unwanted immunological response was detected.…”

Section: Discussionmentioning

confidence: 99%

Etanercept and sulfasalazine, alone and combined, in patients with active rheumatoid arthritis despite receiving sulfasalazine: a double-blind comparison

Combe

2006

Annals of the Rheumatic Diseases

104

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Objective: To compare the efficacy and safety of etanercept and sulfasalazine, alone and in combination, in patients with active rheumatoid arthritis despite sulfasalazine treatment. Methods: A double-blind, randomised study in adult patients with active rheumatoid arthritis despite stable sulfasalazine (2-3 g/day) treatment. The primary end point was a 20% response by the American College of Rheumatology (ACR) criteria at 24 weeks. Results: At baseline, the three treatment groups (sulfasalazine, n = 50; etanercept, n = 103; etanercept and sulfasalazine, n = 101) were comparable for demographic variables and disease activity. Lack of efficacy was the primary reason for discontinuation (sulfasalazine, n = 12; etanercept, n = 1; etanercept and sulfasalazine, n = 4; p,0.001). Significantly more patients receiving etanercept, alone or in combination (74% for each), achieved ACR 20 responses at 24 weeks than those receiving sulfasalazine (28%; p,0.01). Similarly, more patients in the etanercept groups achieved ACR 50 and ACR 70 responses than those in the sulfasalazine group (p,0.01). In the groups receiving etanercept, significant differences in the ACR core components were observed by week 2 compared with those receiving sulfasalazine alone (p,0.01). The incidences of several common adverse events (headache, nausea, asthenia) were lower with etanercept alone than with the combination (p,0.05), but infections and injection site reactions were higher with etanercept alone (p,0.05). The safety profiles of both etanercept treatment groups were comparable with previous experience of etanercept. Conclusions: For all efficacy variables assessed, etanercept alone or in combination with sulfasalazine resulted in substantial and similar improvement in disease activity from baseline to week 24 compared with sulfasalazine alone in patients with active rheumatoid arthritis despite their sulfasalazine treatment. All three treatments were generally well tolerated.

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Section: Discussionmentioning

confidence: 99%

Etanercept and sulfasalazine, alone and combined, in patients with active rheumatoid arthritis despite receiving sulfasalazine: a double-blind comparison

Combe

2006

Annals of the Rheumatic Diseases

104

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“…In contrast, the effects of most earlier DMARD therapies were relatively dose independent. This advance in effective, dose-dependent therapy was followed by the general availability of biologic therapy and the later demonstration that combinations of methotrexate and biologic agents are more effective than either treatment alone in relieving symptoms, improving function, and retarding radiographic erosion (2)(3)(4)(5)(6). Studies have also shown that simultaneous use of multiple DMARDs leads to improved outcomes (7,8), and, in some studies, treatment has resulted in profound improvement, even remission, in many users of biologic agents or combinations of biologic agents and DMARDs (2,6,9).…”

mentioning

confidence: 99%

Resistance of rheumatoid arthritis patients to changing therapy: Discordance between disease activity and patients' treatment choices

Wolfe

Michaud

2007

Arthritis & Rheumatism

116

117

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Objective. Despite advances in rheumatoid arthritis (RA) treatment, patients' decisions regarding therapy often deviate from expert recommendation. This study was undertaken to investigate patients' acceptance and satisfaction with therapy, willingness to change therapy, and reasons for not changing.Methods. Participants (n ‫؍‬ 6,135) completed an 11-item questionnaire concerning treatment preferences. Eight questions assessed reasons for not wanting to change therapy. The contribution of individual predictors was determined by logistic regression analysis.Results. Questionnaire responses showed that 63.8% of the patients would not want to change therapy as long as their condition didn't get worse; 77.3% were satisfied with their medications, while 9.4% were dissatisfied. These assessments were weakly related to RA activity and functional status. Side effects had occurred in 22.4% of the patients during the previous 6 months, and in 65.5% at some period during their lifetime. Predictors of unwillingness to change therapy were satisfaction with RA control, which had an odds ratio ( Conclusion. There is substantial discrepancy between declared satisfaction with therapy and measured RA activity and functional status. Most RA patients are satisfied with their therapy, even many with abnormal scores. Fear of loss of control of RA and fear of side effects are major patient concerns. Maintenance of current status, rather than future improvement, appears to be a high priority for patients.

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“…In the trials comparing combination therapy with monotherapy, glucocorticoid use was increased in the combination arm, which might explain the superiority of combination therapy. 19 Therefore, clinicians might vary in their threshold to use combination DMARDs. Although NICE recommends combination treatment, European 16 and American guidelines, 20 which appraised the same trials, suggest monotherapy, which puts in context the finding that less than half of patients were offered combination therapy.…”

Section: Resultsmentioning

confidence: 99%

To what extent is NICE guidance on the management of rheumatoid arthritis in adults being implemented in clinical practice? A regional survey

et al. 2013

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-Rheumatoid arthritis (RA) is a chronic disease associated with significant morbidity. The 2009 NICE guidance advises on the management of patients with RA. In this study, we undertook a survey to assess the implementation of the guidance into practice across the Midlands. In total, 19 rheumatology units participated, of which nine have designated early inflammatory arthritis clinics (EIAC). Data for 311 patients with RA attending clinics were collected during a two week period. The median time from symptom onset to first visit was four months. Of the patients, 95.6% were seen within 12 weeks of referral. Of those seen in EIAC, 75.9% had erosions documented on X-rays versus 49.4% of non-EIAC patients. In addition, 57.9% of patients were offered combination diseasemodifying antirheumatic drugs (DMARD) therapy in EIAC, versus 30.4% in non-EIAC units. Monthly disease-activity scores were calculated more in patients attending EIAC than non-EIAC units (51.1% versus 25.4%). Based on our results, there is significant regional variation in implementation of the NICE guidance. In addition, patients with RA attending EIACs are more likely to receive a treat-to-target approach.

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Superior efficacy of combination therapy for rheumatoid arthritis: Fact or fiction?

Cited by 76 publications

References 47 publications

Etanercept and sulfasalazine, alone and combined, in patients with active rheumatoid arthritis despite receiving sulfasalazine: a double-blind comparison

Etanercept and sulfasalazine, alone and combined, in patients with active rheumatoid arthritis despite receiving sulfasalazine: a double-blind comparison

Resistance of rheumatoid arthritis patients to changing therapy: Discordance between disease activity and patients' treatment choices

To what extent is NICE guidance on the management of rheumatoid arthritis in adults being implemented in clinical practice? A regional survey

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