Real-world effectiveness of select biologic and DMARD monotherapy and combination therapy in the treatment of rheumatoid arthritis: results from the RADIUS observational registry

OBJECTIVE: To evaluate the effectiveness of select biologics, methotrexate (MTX), and other disease-modifying anti-rheumatic drugs (DMARDs) in the management of adult rheumatoid arthritis (RA) in routine clinical practice. RESEARCH DESIGN AND METHODS: RADIUS (Rheumatoid Arthritis DMARD Intervention and Utilization Study) comprises two prospective, 5-year, observational registries of over 10 000 patients. Over 4600 patients who initiated MTX or a biologic regimen (etanercept [ETN], infliximab [INF], ETN + MTX, and INF + MTX) and who had at least one on-regimen, follow-up evaluation, were included in this analysis. Adalimumab was not included because it had not yet received FDA approval at RADIUS initiation. Other common DMARD regimens (N = 762) were also compared with MTX. Patients who initiated less commonly used regimens, such as anakinra or cyclosporine, and those who did not have at least one on-regimen, follow-up evaluation, were not eligible for this analysis. Because ESR/CRP measurements were often not available, a modified ACR20 response (mACR20), defined as three out of four response criteria excluding ESR/CRP, was used to assess response at 12 months. Logistic regression analysis was performed to control for baseline covariates that may affect outcomes. MAIN OUTCOME MEASURES: The primary endpoint was the proportion of patients who achieved a mACR20 response at 12 months post-RADIUS entry. RESULTS: After adjusting for baseline covariates, patients receiving either ETN + MTX or ETN monotherapy were more likely to achieve a mACR20 response at 12 months than patients receiving MTX alone (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.09-1.52; p < 0.01 and OR 1.23, 95% CI 1.02-1.47; p < 0.05, respectively). Conversely, patients treated with MTX + leflunomide (LEF) were less likely to achieve a mACR20 response than those receiving MTX alone (OR 0.68, 95% CI 0.48-0.96; p < 0.05). Significant differences were not observed between patients receiving MTX alone and either INF + MTX, MTX + hydroxychloroquine, MTX + hydroxychloroquine + sulfasalazine, INF monotherapy, or LEF monotherapy. CONCLUSION: These data from routine rheumatology clinical practice settings highlight the effectiveness of common biologic and DMARD therapies, and provide additional data beyond those of randomized, controlled trials.     

Real-world effectiveness of select biologic and DMARD monotherapy and combination therapy in the treatment of rheumatoid arthritis: results from the RADIUS observational registry

ABSTRACT

Objective:?To evaluate the effectiveness of select biologics, methotrexate (MTX), and other disease-modifying anti-rheumatic drugs (DMARDs) in the management of adult rheumatoid arthritis (RA) in routine clinical practice.

Research design and methods:?RADIUS (Rheumatoid Arthritis DMARD Intervention and Utilization Study) comprises two prospective, 5‐year, observational registries of over 10?000 patients. Over 4600 patients who initiated MTX or a biologic regimen (etanercept [ETN], infliximab [INF], ETN + MTX, and INF + MTX) and who had at least one on-regimen, follow-up evaluation, were included in this analysis. Adalimumab was not included because it had not yet received FDA approval at RADIUS initiation. Other common DMARD regimens (?N = 762) were also compared with MTX. Patients who initiated less commonly used regimens, such as anakinra or cyclosporine, and those who did not have at least one on-regimen, follow-up evaluation, were not eligible for this analysis. Because ESR/CRP measurements were often not available, a modified ACR20 response (mACR20), defined as three out of four response criteria excluding ESR/CRP, was used to assess response at 12 months. Logistic regression analysis was performed to control for baseline covariates that may affect outcomes.

Main outcome measures:?The primary endpoint was the proportion of patients who achieved a mACR20 response at 12 months post-RADIUS entry.

Results:?After adjusting for baseline covariates, patients receiving either ETN + MTX or ETN monotherapy were more likely to achieve a mACR20 response at 12 months than patients receiving MTX alone (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.09–1.52; p < 0.01 and OR 1.23, 95% CI 1.02–1.47; p < 0.05, respectively). Conversely, patients treated with MTX + leflunomide (LEF) were less likely to achieve a mACR20 response than those receiving MTX alone (OR 0.68, 95% CI 0.48–0.96; p < 0.05). Significant differences were not observed between patients receiving MTX alone and either INF + MTX, MTX + hydroxychloroquine, MTX + hydroxychloroquine + sulfasalazine, INF monotherapy, or LEF monotherapy.

Conclusion:?These data from routine rheumatology clinical practice settings highlight the effectiveness of common biologic and DMARD therapies, and provide additional data beyond those of randomized, controlled trials.     

Comparative effectiveness of azathioprine in Crohn's disease and ulcerative colitis: prospective, long-term, follow-up study of 394 patients

Background The long‐term efficiacy for thiopurinic drugs in Crohn’s disease (CD), and particularly in ulcerative colitis (UC), has been insufficiently studied. Aim To evaluate prospectively and compare the long‐term effectiveness of azathioprine (AZA) in CD and UC. Methods Three hundred and ninety‐four AZA treated patients were included consecutively included. Truelove‐modified index and CDAI were used to assess effectiveness. Hospitalizations and surgical procedures were recorded. Results Two hundred and thirty‐eight patients with CD and 156 with UC received AZA for a median of 38 months. Effectiveness: Partial response/remission was achieved in 34%/49% of CD patients and in 47%/42% of UC (nonstatistically significant differences). Steroid treatment: Prior to AZA, 49% of CD patients were receiving steroids, whereas only 8% needed steroids after therapy (P < 0.001). Corresponding figures in UC patients were 39% vs. 9% (P < 0.001). Hospitalizations: Prior to AZA, the rate of hospitalizations in CD was 0.190 per‐patient‐year, while after treatment, it decreased to 0.099 (P < 0.001). Corresponding hospitalization rates in UC were 0.108 vs. 0.038 (P < 0.001). Surgery: The rate of surgery in CD prior/after AZA was 0.038/0.011 per‐patient‐year (P < 0.001). The number of surgical interventions in UC prior/after AZA treatment was 26/0 (the rate per‐patient‐year was 0.018/0) (P < 0.001). Conclusions Our results confirm the effectiveness of AZA in inflammatory bowel disease, not only in the short term but also in the long term, resulting in a steroid sparing effect and in both a reduction in the number of hospitalizations and surgical procedures. AZA is similarly effective for both CD and UC patients.     

The effectiveness of budesonide therapy for Crohn's disease

AIM: To assess the effectiveness and safety of budesonide in comparison to corticosteroids, 5-aminosalicylic acid (5-ASA), or placebo for inducing remission of active Crohn's disease and for maintaining remission. STUDY SELECTION CRITERIA: Randomized controlled trials comparing budesonide to corticosteroids, 5-ASA products or placebo were included. Trials had to report on the effectiveness of treatment (defined as decreasing or maintaining Crohn's Disease Activity Index, CDAI, scores < or = 150) or adverse events. DATA ANALYSIS: After assessing the validity of study design and independent, duplicate data extraction from selected trials, summary relative risks (RR) were calculated for each outcome. A test of heterogeneity was also calculated for each outcome using a random effects model. RESULTS: Budesonide was more likely to induce remission than placebo (RR=1.82, 95% CI: 1.15-2.88) or 5-ASA (RR=1.73, 95% CI: 1.26-2.39), although only one trial compared budesonide to 5-ASA products. Although budesonide induced remission less frequently than conventional corticosteroids (RR=0.87, 95% CI: 0.76-0.995), there was no significant difference between conventional corticosteroids and budesonide for inducing remission among patients with a low disease activity (initial CDAI=200-300). Budesonide was significantly less likely to cause corticosteroid-associated adverse events than conventional corticosteroids (RR=0.65, 95% CI: 0.53-0.80). No significant difference in total adverse events or corticosteroid-associated adverse events was demonstrated between budesonide and 5-ASA or placebo. CONCLUSION: Budesonide is significantly more effective than placebo or 5-ASA for inducing remission of active Crohn's disease. Although budesonide is 13% less effective for the induction of remission in active Crohn's disease than conventional corticosteroids, it is less likely to cause corticosteroid-related adverse effects. Budesonide is ineffective in maintaining remission.     

Mycophenolate mofetil for Crohn's disease: short-term efficacy and long-term outcome

AIM: To assess the long-term efficacy of the antimetabolite agent mycophenolate mofetil in patients with Crohn's disease. METHODS: Twenty patients with complicated Crohn's disease were treated with mycophenolate mofetil, 1 g b.d., for up to 7 years. Twelve patients were intolerant to azathioprine, seven were resistant to azathioprine and one had a history of mesalazine-induced pancreatitis. The response to mycophenolate mofetil was determined by calculation of the Harvey-Bradshaw index, the ability to taper steroids and the grading of fistula activity. RESULTS: After 6 months, 11 of the 20 patients had responded. Seven of the 11 responders relapsed after a median of 18 months, three have an ongoing response at month 17, 19 and 82, and one discontinued mycophenolate mofetil owing to toxicity. After initial treatment failure, mycophenolate mofetil was continued in 12 of 17 patients for a further 2-41 months without inducing a stable remission. Mycophenolate mofetil was of benefit in nine of the 12 patients intolerant to azathioprine and in two of the seven patients resistant to azathioprine. Perianal fistulas improved in seven of eight patients; five of the seven subsequently deteriorated, but only one due to reactivated perianal disease. CONCLUSIONS: Mycophenolate mofetil was initially effective in a sizeable fraction of patients with complicated Crohn's disease, but relapse within 18 months was common. Nevertheless, mycophenolate mofetil could be a useful alternative in patients intolerant to azathioprine.     

Maintenance infliximab does not result in increased abscess development in fistulizing Crohn's disease: results from the ACCENT II study

BACKGROUND: Rapid fistula healing may predispose Crohn's disease patients to abscess development. AIM: Data from ACCENT II were analysed to determine whether fistula-related abscess development is affected by infliximab exposure. METHODS: Following infliximab 5 mg/kg infusions at weeks 0, 2 and 6, patients were evaluated for fistula response for two consecutive visits at least 4 weeks apart. Patients (N = 282) were randomized at week 14 to either placebo or infliximab 5 mg/kg every 8 weeks through week 46. If response was lost at or after week 22, patients could crossover to a 5 mg/kg higher infliximab dose. Fistula-related abscesses were diagnosed by physical examination or by imaging procedures according to usual practice. RESULTS: Infliximab exposure was approximately twofold higher for the infliximab maintenance group. Twenty-one (15%) patients in the infliximab maintenance group had at least one newly developed fistula-related abscess compared with 27 (19%) in the placebo maintenance group (P = 0.526). The proportion of patients with a new fistula-related abscess was similar regardless of whether or not patients crossed over to a 5 mg/kg higher infliximab dose. The number of fistula-related abscesses diagnosed over time did not differ between groups. CONCLUSION: Abscess development in patients with fistulizing Crohn's disease is not dependent on cumulative infliximab exposure.     

Clinical and resource-use outcomes of risperidone long-acting injection in recent and long-term diagnosed schizophrenia patients: results from a multinational electronic registry

ABSTRACT

Background: Non-adherence to pharmacological treatment leading to frequent relapses and rehospitalizations is a major issue of concern among schizophrenia patients, especially those who are recently diagnosed. Risperidone long-acting injection (RLAI) has been shown to be efficacious, improve compliance, and increase long-term retention rate on therapy.

Objective: To determine clinical outcomes and hospitalizations before and after the initiation of RLAI among schizophrenia patients with recent (≤2 years) diagnosis relative to those who had long-term (> 2 years) diagnosis.

Research design and methods: The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is an observational study of patients with schizophrenia who start treatment with RLAI. Data were recorded at baseline, retrospectively for the 12 months prior to baseline, and prospectively every 3 months for 24 months. Data on patients with a defined length of diagnosis were pooled from eight countries.

Main outcome measures: Clinical Global Impression of Illness Severity (CGI-S), Global Assessment of Functioning (GAF) scores, and hospitalization data were key outcomes.

Results: The magnitude of improvement in CGI-S scores was greater in the recent versus long-term diagnosis group [Δ ?1.48 vs. Δ ?0.95 (12 months); Δ ?1.6 vs. Δ ?1.09 (24 months)]. There were parallel improvements in GAF scores [Δ 19.4 vs. Δ 13.7 (12 months); Δ 22.3 vs. Δ 16.8 (24 months)]. The decline in the proportion of patients hospitalized from the retrospective to the prospective period was greater in the recent versus long-term diagnosis group (Δ ?36.0 vs. Δ ?19%, respectively) at 12 months. This was also true for the number of hospital stays (Δ ?0.6 vs. Δ ?0.3, respectively) and length of stay (days) (Δ ?20.9 vs. Δ ?6.9, respectively) at 12 months. Common adverse events in both groups included psychiatric, gastrointestinal, musculoskeletal and reproductive system and breast disorders.

Conclusions: Treatment with RLAI is associated with improved outcomes in recently diagnosed and chronic patients. However, the magnitude of improvement was higher in recently diagnosed patients.     

Randomised clinical trial: certolizumab pegol for fistulas in Crohn's disease - subgroup results from a placebo-controlled study

Aliment Pharmacol Ther 2011; 33: 185–193

Summary

Background Treatment options for fistulizing Crohn’s disease (CD) are limited. Aim To examine whether fistula closure is maintained at week 26 following treatment with certolizumab pegol. Methods Patients with draining fistulas at baseline from PRECiSE 2 (n = 108) received open‐label induction with certolizumab pegol 400 mg at weeks 0 (baseline), 2 and 4. Response was defined as ≥100‐point decrease from baseline in the Crohn’s Disease Activity Index. Nonresponders (50/108) were excluded. At week 6, responders with draining fistulas (N = 58) were randomised to certolizumab pegol 400 mg (n = 28) or placebo (n = 30) every 4 weeks across weeks 8–24. Fistula closure was evaluated throughout the study, with a final assessment at week 26. Results The majority of patients (55/58) had perianal fistula. At week 26, 36% of patients in the certolizumab pegol group had 100% fistula closure compared with 17% of patients receiving placebo (P = 0.038). Protocol‐defined fistula closure (≥50% closure at two consecutive post‐baseline visits ≥3 weeks apart) was not statistically significant (P = 0.069) with 54% and 43% of patients treated with certolizumab pegol and placebo achieving this end point, respectively. Conclusion Continuous treatment with certolizumab pegol improves the likelihood of sustained perianal fistula closure compared with placebo.     

5-aminosalicylic acid in the prevention of relapses of Crohn's disease in remission: a long-term study.

The aim of the study was to evaluate the efficacy of 5-aminosalicylic acid (5-ASA) in maintaining the remission in patients with inactive Crohn's disease over a period of three years, using either the Crohn's Disease Activity Index (CDAI) and or the Laboratory Index (LI). Thirty-eight patients entered in the study; 20 received 5-ASA 1.6 g/day and 18 no specific therapy. The patients were followed for three years. Of the patients, 86% presented a relapse, 80% in the 5-ASA group and 94% in the control group. Two patients requested surgical therapy. All patients with clinical relapse had CDAI greater than 150 and LI greater than 100. 5-Aminosalicylic acid was well tolerated and was able to protect from relapse up to 60% of the patients in the first year of therapy. When treatment with 5-ASA is prolonged for periods longer than one year a progressive increase in the number of patients who present relapse can be observed, but of the 5-ASA group, 80% of relapses occurred in the three years whereas the control group showed 94% relapses at the end of the first year.