Differences in disease activity measures in patients with rheumatoid arthritis who achieved DAS, SDAI, or CDAI remission but not Boolean remission.

OBJECTIVES: In patients with rheumatoid arthritis (RA), remission may be assessed by various composite measures. We assessed achievement of remission as defined by Boolean criteria, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and 28-joint Disease Activity Score using C-reactive protein (DAS28[CRP]) and determined the components that limit patients in SDAI, CDAI, or DAS28(CRP) remission from achieving Boolean remission. METHODS: The proportions of patients achieving Boolean, SDAI, CDAI, or DAS28(CRP) remission were calculated for 3 trials: PREMIER and OPTIMA in patients with early RA and DE019 in patients with established RA. At the first visit that remission was recorded during the first 52 weeks of the trial, the following were assessed: swollen/tender joint count at 28 and 66/68 joints, CRP, Patient's/Physician's Global Assessment (PGA/PhGA), SDAI, DAS28(CRP), and Health Assessment Questionnaire-Disability Index. RESULTS: The majority of patients (61-66%) who achieved SDAI or CDAI remission also attained Boolean remission. Although DAS28(CRP) remission was most frequently attained, 74-77% of patients in DAS28(CRP) remission did not achieve Boolean remission. Compared with patients in Boolean remission, patients in SDAI or CDAI remission but not Boolean remission had higher PGA scores, while patients with DAS28(CRP) remission but not Boolean remission had higher joint counts, and PGA and PhGA scores. CONCLUSIONS: Differences in PGA limit patients in SDAI/CDAI remission from meeting the Boolean remission criteria, suggesting that these criteria otherwise can be used interchangeably. In contrast, patients in DAS28(CRP) remission are limited by differences in multiple disease activity measures from achieving Boolean remission.

Effect of disease duration and prior disease-modifying antirheumatic drug use on treatment outcomes in patients with rheumatoid arthritis.

OBJECTIVES: To determine if disease duration and number of prior disease-modifying antirheumatic drugs (DMARDs) affect response to therapy in patients with established rheumatoid arthritis (RA). METHODS: Associations between disease duration or number of prior DMARDs and response to therapy were assessed using data from two randomised controlled trials in patients with established RA (mean duration, 11 years) receiving adalimumab+methotrexate. Response to therapy was assessed at week 24 using disease activity outcomes, including 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)), Simplified Disease Activity Index (SDAI) and Health Assessment Questionnaire Disability Index (HAQ-DI), and proportions of patients with 20%/50%/70% improvement in American College of Rheumatology (ACR) responses. RESULTS: In the larger study (N=207), a greater number of prior DMARDs (>2 vs 0-1) was associated with smaller improvements in DAS28(CRP) (-1.8 vs -2.2), SDAI (-22.1 vs -26.9) and HAQ-DI (-0.43 vs -0.64) from baseline to week 24. RA duration of >10 years versus <1 year was associated with higher HAQ-DI scores (1.1 vs 0.7) at week 24, but results on DAS28(CRP) and SDAI were mixed. A greater number of prior DMARDs and longer RA duration were associated with lower ACR response rates at week 24. Data from the second trial (N=67) generally confirmed these findings. CONCLUSIONS: Number of prior DMARDs and disease duration affect responses to therapy in patients with established RA. Furthermore, number of prior DMARDs, regardless of disease duration, has a limiting effect on the potential response to adalimumab therapy.

Predictors of disease activity and structural progression after treatment with adalimumab plus methotrexate or continued methotrexate monotherapy in patients with early rheumatoid arthritis and suboptimal response to methotrexate.

OBJECTIVES: Methotrexate is considered to be first-line therapy for rheumatoid arthritis (RA). However, a substantial proportion of treated patients do not achieve the desired goals of therapy. This analysis aimed to identify predictors of insufficient response to methotrexate in patients with early RA. METHODS: The Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab (OPTIMA) and PREMIER studies in patients with RA for <1 and <3 years, respectively, examined the efficacy of methotrexate and adalimumab in methotrexate-naive patients. This post hoc analysis included patients for whom initial methotrexate monotherapy was not successful after 6 months. Candidate predictors of insufficient response and clinically relevant radiographic progression (CRRP) included demographics, baseline disease characteristics and time-averaged disease variables over a 12-week interval. In OPTIMA, adalimumab was added to therapy after insufficient treatment response; in PREMIER, initial methotrexate therapy was continued; clinical, functional and radiologic outcomes were assessed after 1 year. RESULTS: Baseline 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)) and time-averaged DAS28(CRP) over 4, 8 and 12 weeks were the strongest predictors of insufficient response to methotrexate and CRRP. Addition of adalimumab to methotrexate therapy was associated with better clinical, functional and radiographic outcomes after 1 year compared with continuing on methotrexate monotherapy. CONCLUSIONS: In patients with early RA, baseline disease characteristics and early disease activity can predict response to methotrexate treatment and radiographic progression at 6 months. The addition of adalimumab at 6 months after methotrexate failure is associated with improved outcomes. These results support treatment-to-target strategies and timely adaptation of therapy in patients with early RA. TRIAL REGISTRATION NUMBER: NCT00420927, NCT00195663; Post-results.

Long-term use of adalimumab as monotherapy after attainment of low disease activity with adalimumab plus methotrexate in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate long-term clinical, functional and radiographic outcomes in an open-label extension (OLE) study in patients with rheumatoid arthritis (RA) receiving adalimumab monotherapy or adalimumab+methotrexate following attainment of low disease activity (LDA) with adalimumab+methotrexate. METHODS: Methotrexate-naive patients with early RA were randomised to adalimumab, methotrexate or adalimumab +methotrexate in a double-blind, 2-year study. Patients who completed the study and achieved LDA (28-joint Disease Activity Score using C reactive protein (DAS28(CRP)<3.2) could receive adalimumab monotherapy for up to 8 additional years in the OLE; open-label methotrexate could be added per investigator's discretion. This post hoc analysis included data up to OLE year 3 (study year 5) from patients receiving adalimumab+methotrexate who achieved LDA at year 2 followed by adalimumab monotherapy or methotrexate reinitiation. Normal physical function was defined as Disability Index of the Health Assessment Questionnaire <0.5 and radiographic non-progression as change in modified total Sharp score ≤0.5. RESULTS: Of 140 patients initiating adalimumab monotherapy, 84 (60%) received adalimumab only (methotrexate non-use) and 56 (40%) reinitiated methotrexate (methotrexate use) during OLE treatment. Median (IQR) time to first methotrexate use was 5.1 (0.1-31.4) weeks. Among methotrexate users, 61% retained LDA, 48% achieved DAS28(CRP) <2.6, 45% had normal physical function and 46% had no radiographic progression at year 5; for non-users, 63%, 50%, 58% and 50%, respectively, achieved these milestones. Adverse event rates were similar between methotrexate non-use and use patients. CONCLUSIONS: Adalimumab monotherapy effectively maintained good clinical, functional and radiographic outcomes for up to 3 additional years in ≥50% of patients who attained LDA after 2 years of adalimumab+methotrexate therapy. TRIAL REGISTRATION NUMBER: NCT00195663; Post-results.

Low Hemoglobin and Radiographic Damage Progression in Early Rheumatoid Arthritis: Secondary Analysis From a Phase III Trial.

OBJECTIVE: To study low blood hemoglobin concentrations as a predictor of radiographic damage progression in patients with rheumatoid arthritis (RA). METHODS: Post hoc analyses were performed in patients from the PREMIER trial with early RA undergoing 2 years of adalimumab (ADA), methotrexate (MTX), or ADA + MTX combination therapy. Low disease activity was defined as a score <3.2 on the 28-joint Disease Activity Score using the C-reactive protein level (DAS28-CRP), and clinical response by the American College of Rheumatology criteria for 20% improvement at week 24. Baseline or mean hemoglobin concentrations over time, or anemia as defined using sex-specific World Health Organization criteria, were analyzed in mixed-effects models for longitudinal data in men and women as predictors of progressive joint damage, as measured by the modified total Sharp/van der Heijde score (ΔSHS). Data were adjusted for treatment and other patient characteristics, including the DAS28-CRP. RESULTS: Baseline hemoglobin was inversely associated with ΔSHS in adjusted analyses (P < 0.05 for both sexes). Baseline anemia predicted greater ΔSHS in MTX-treated patients over 104 weeks, and in ADA- and combination-treated patients over 26 weeks. Lower hemoglobin concentrations over time, as well as time with anemia, were associated with greater damage progression (P < 0.001). The effect of low hemoglobin concentrations on joint damage progression remained significant, even in patients achieving low disease activity. CONCLUSION: Low hemoglobin is a DAS28-CRP-independent predictor of radiographic joint damage progression in MTX-treated patients with early RA. This effect decreases over time in ADA- and combination-treated patients, and in clinical responders irrespective of treatment modality.

Testing treat-to-target outcomes with initial methotrexate monotherapy compared with initial tumour necrosis factor inhibitor (adalimumab) plus methotrexate in early rheumatoid arthritis.

OBJECTIVES: To compare responses in patients with early rheumatoid arthritis (RA) initially treated with the tumour necrosis factor inhibitor (TNFi) adalimumab+methotrexate (MTX) versus MTX monotherapy who may have continued receiving MTX or switched to adalimumab rescue therapy after inadequate response to MTX. METHODS: OPTIMA enrolled MTX-naive patients with active RA for <1 year. This post hoc analysis determined the proportion of patients, stratified by initial treatment, who achieved 28-joint modified Disease Activity Score based on C reactive protein <3.2, normal function and/or no radiographic progression at weeks 26, 52 and 78. RESULTS: Significantly greater proportions of patients initially treated with adalimumab+MTX (n=466) compared with MTX monotherapy (n=460) achieved good clinical (53% vs 30%), functional (45% vs 33%) and radiographic (87% vs 72%) outcomes at week 26. From weeks 26 to 78, adalimumab rescue patients achieved similar clinical and functional outcomes versus patients initially treated with adalimumab+MTX. However, significantly more patients initially treated with adalimumab+MTX had no radiographic progression at weeks 52 and 78 versus patients initially treated with MTX (both timepoints: 86% vs 72%). CONCLUSIONS: In early RA, starting with MTX monotherapy and adding TNFi after 26 weeks yields similar longer term clinical results as starting with TNFi+MTX combination therapy but allows a small but significant accrual of radiographic damage.

Achieving comprehensive disease control in patients with early and established rheumatoid arthritis treated with adalimumab plus methotrexate versus methotrexate alone.

OBJECTIVE: To evaluate the achievement of comprehensive disease control (CDC) following 1 year of treatment with adalimumab+methotrexate versus methotrexate alone and whether early achievement of remission (at week 24 or 26) is associated with CDC at week 52 in patients with either early or established rheumatoid arthritis (RA). METHODS: Post hoc analyses were conducted in three clinical studies assessing treatment with adalimumab+methotrexate: DE019 (NCT00195702) enrolled patients with established RA who were methotrexate inadequate responders; OPTIMA (NCT00420927) and PREMIER (NCT00195663) enrolled methotrexate-naive patients with early RA. In OPTIMA, patients not achieving stable low disease activity at weeks 22 and 26 in the placebo+methotrexate group could receive open-label adalimumab+methotrexate for 52 weeks (Rescue ADA arm). CDC was defined as the simultaneous achievement of clinical remission (DAS28(CRP)<2.6), normal function (HAQ-DI<0.5) and absence of radiographic progression (ΔmTSS≤0.5). RESULTS: Regardless of disease duration, significantly more patients receiving adalimumab+methotrexate achieved CDC compared with methotrexate alone. In the adalimumab+methotrexate group, a numerically greater proportion of patients with early RA (~25%) versus established RA (14%) achieved CDC at 1 year; achievement of CDC was notably greater among patients who met criteria for remission at week 24 or 26 (~50% of patients with early RA and 39% with established RA). CONCLUSION: Treatment with adalimumab+methotrexate increases the likelihood of achieving CDC in patients with either early or established RA. Clinical remission at week 24 or 26 is associated with achievement of CDC at week 52. TRIAL REGISTRATION NUMBER: DE019 (NCT00195702), OPTIMA (NCT00420927), PREMIER (NCT00195663); Post-results.

Final 10-year effectiveness and safety results from study DE020: adalimumab treatment in patients with rheumatoid arthritis and an inadequate response to standard therapy.

OBJECTIVE: To evaluate the long-term effectiveness and safety of 10 years of adalimumab (ADA) treatment in DMARD-refractory RA patients and to analyse efficacy based on RF status and baseline disease duration. METHODS: DE020 was a multicentre, phase 3, open-label continuation study. Adult RA patients who received s.c. ADA (40 mg every other week or monthly) in one of four early assessment studies could receive ADA for ≤10 years in DE020. Assessments included the 28-joint DAS with CRP (DAS28-CRP), Simplified Disease Activity Index (SDAI), HAQ Disability Index (HAQ-DI) and safety as events per 100 patient-years. RESULTS: Of 846 enrolled patients, mean age at baseline was 55.6 years, 78.1% were women, mean disease duration was 11.7 years and 27.0% were RF(-). Among 286 (33.8%) patients who completed 10 years of ADA, 168/236 (71.2%) achieved DAS28-CRP ≤3.2, 101/238 (42.4%) achieved HAQ-DI <0.5 and 90/241 (37.3%) achieved DAS28-CRP ≤3.2 plus HAQ-DI <0.5. DAS28-CRP- or SDAI-based remission was observed in 135/236 (57.2%) and 70/236 (29.7%) patients, respectively. Effectiveness outcomes were similar regardless of RF status. Higher proportions of patients with shorter vs longer baseline disease duration (≤2 vs >2 years) achieved HAQ-DI <0.5 (60.6% vs 39.5%; P = 0.023) and DAS28-CRP ≤3.2 plus HAQ-DI <0.5 (58.1% vs 32.5%; P = 0.006). Adverse events (317.2 events per 100 patient-years) during ADA exposure were consistent with the expected safety profile for TNF inhibitors. CONCLUSION: ADA led to sustained clinical and functional responses in the 33.8% of treatment-refractory RA patients who completed 10 years of treatment. Patients with shorter disease duration achieved better outcomes, highlighting the need for early treatment. No unexpected safety findings were observed. TRIAL REGISTRATION: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT00195650.

Existing joint erosions increase the risk of joint space narrowing independently of clinical synovitis in patients with early rheumatoid arthritis.

INTRODUCTION: Clinical synovitis is often associated with damage to bone and cartilage. Previous data have suggested that joint erosions (JE) are more prevalent than joint space narrowing (JSN) and that the two processes are partly independent of each other. The objective of this study was to evaluate whether the presence of JE in an individual joint can lead to development of JSN and if existing JSN leads to new onset of JE, in the absence of synovitis. METHODS: The Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFα Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER) enrolled early rheumatoid arthritis (RA) patients who were randomized to one of three treatments: methotrexate (MTX), adalimumab (ADA), or ADA + MTX. All evaluable joints with JE and JSN measures at 26 and 52 weeks and synovitis assessments from week 26 to 52 were included. Synovitis was assessed every 2-8 weeks by swollen joint counts between weeks 26 and 52. Radiographs were taken at week 26 and 52. Two readers, blinded to time and sequence, scored 14 bilateral joints individually for JE and JSN. Multivariate logistic modeling was used to characterize the dependence of JE/JSN onset at 52 weeks. Analyses were performed based on treatment arm and were also performed within individual joints. RESULTS: JE and swelling were independently and comparably associated with onset of JSN at week 52. Assessment by individual joints indicated that existing JE, independent of swelling, was significantly associated with JSN onset in higher proportions of metatarsophalangeal (MTP; 7/10) than proximal interphalangeal (PIP; 1/8) or metacarpophalangeal (MCP; 1/10) joints. Treatment with ADA + MTX prevents JE/JSN progression independently of its ability to suppress synovitis and limits JE/JSN onset and progression in joints with existing damage. CONCLUSIONS: Existing JE predisposes individual joints to development of JSN independently of synovitis in the same joint. Weight-bearing MTP joints with JE may be at increased risk for JSN when compared with MCPs and PIPs. TRIAL REGISTRATION: Clinicaltrials.gov NCT00195663. Registered 13 September 2005.

Analysis of integrated radiographic data from two long-term, open-label extension studies of adalimumab for the treatment of rheumatoid arthritis.

OBJECTIVE: A longitudinal integration approach evaluated all radiographic scores assessed over 10 years, rather than only completer data, from 2 studies of adalimumab (ADA) for rheumatoid arthritis (RA). METHODS: The DE019 (methotrexate [MTX]-inadequate responders, longstanding RA) and PREMIER (MTX-naive, early RA) studies, respectively, had 1- or 2-year double-blind periods followed by 9- or 8-year open-label extensions (OLEs). Patients received ADA ± MTX in both OLEs. Radiographic progression was assessed using change from baseline in modified total Sharp score (ΔmTSS). A mixed-effects model was used post hoc to evaluate repeated measurements of different data campaigns and to estimate ΔmTSS through up to 10 years of treatment based on original randomization groups (placebo [PBO] + MTX or standard dose ADA + MTX). RESULTS: Data from patients with baseline and ≥1 postbaseline radiograph were included (n = 327 for DE019; n = 452 for PREMIER). Integrated and 10-year completer ΔmTSS progression curves differed slightly. In DE019, for patients originally assigned PBO + MTX, accrued ΔmTSS at year 10 was 6.6 units (integrated model) and 6.2 units (completers). For patients originally assigned ADA + MTX, accrued ΔmTSS was 0.9 units by integrated analysis and 0.7 units in completers. In PREMIER, for patients originally assigned PBO + MTX, accrued ΔmTSS at year 10 was 11.2 units (integrated analysis) and 11.0 units (completers). For patients originally assigned ADA + MTX, accrued ΔmTSS was 5.1 units (integrated analysis) and 4.0 units (completers). A higher radiographic progression rate was observed in patients who received delayed versus immediate ADA + MTX treatment. CONCLUSIONS: Longitudinal integrated analysis provided robust estimates of radiographic progression that only slightly differed from completers-only scores and confirmed the effects.

Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial.

OBJECTIVE: CONCERTO was a randomised, double-blind, parallel-armed study of methotrexate (MTX) in combination with adalimumab to assess whether an increasing trend of efficacy and decreased safety exists when increasing MTX dose in patients with early rheumatoid arthritis (RA). METHODS: Early, biologic and MTX-naive RA patients (N=395) were evenly randomised to open-label adalimumab (40 mg every other week) plus weekly blinded 2.5, 5, 10 or 20 mg MTX for 26 weeks. Clinical, radiographic and functional outcomes were analysed using two-sided linear trend tests or one-way analysis of covariance. RESULTS: Statistically significant increasing trends were observed in the proportion of patients achieving the primary endpoint, 28-joint count disease activity score with C reactive protein (DAS28(CRP)) <3.2 (42.9%, 44.0%, 56.6% and 60.2% for 2.5, 5, 10 or 20 mg/week MTX, respectively), DAS28(CRP) <2.6 and American College of Rheumatology 50/70/90 responses with increasing doses of MTX in combination with adalimumab. No statistical differences in minimal clinically important differences in physical function were detected. Statistically significant trends for achieving low disease activity and remission were demonstrated with increasing MTX dose by validated clinical indices; differences comparing 10 and 20 mg MTX were minimal. Adalimumab serum concentrations increased with ascending dose up to 10 mg MTX. More patients experienced infectious adverse events with increasing MTX dose. CONCLUSIONS: Increasing doses of MTX in combination with adalimumab demonstrated a statistically significant trend in improved clinical outcomes that mimicked the adalimumab pharmacokinetic profile. In early RA patients initiating adalimumab combination therapy, efficacy of 10 and 20 mg/week MTX appeared equivalent.

Longterm effect of delaying combination therapy with tumor necrosis factor inhibitor in patients with aggressive early rheumatoid arthritis: 10-year efficacy and safety of adalimumab from the randomized controlled PREMIER trial with open-label extension.

OBJECTIVE: To evaluate the longterm safety of adalimumab administered with or without methotrexate (MTX) and compare the efficacy of combination therapy initialization to adalimumab or MTX monotherapy initialization during the open-label extension (OLE) of the PREMIER trial (ClinicalTrials.gov Identifier:NCT00195663). METHODS: Patients with early rheumatoid arthritis (RA) were randomized to receive blinded adalimumab + MTX, adalimumab alone, or MTX alone for 2 years. Following the double-blinded period, patients enrolling in the OLE were given adalimumab for up to 8 additional years, beginning as monotherapy; investigators could add MTX at their discretion. Results for clinical, functional, and radiographic progression were collected for up to 10 years of treatment. RESULTS: During the PREMIER OLE, 250/497 patients (50.3%) completed the trial without new safety signals arising. Similar proportions of patients discontinued the trial early, although lack of efficacy was reported less often for patients initially randomized to the adalimumab + MTX arm (9.3%; 21.2%, and 23.7% for adalimumab and MTX monotherapies, respectively). Clinical and functional disease control was maintained throughout the trial. Patients initially randomized to adalimumab + MTX displayed better outcomes, particularly in prevention of radiographic progression (modified total Sharp score change = 4.0, 8.8, 11.0 at Year 10 for the initial adalimumab + MTX, adalimumab, and MTX arms, respectively). CONCLUSION: Intensive therapy with adalimumab + MTX combination in patients with early RA has longterm benefits compared to patients initiating with 2-year adalimumab or MTX monotherapy that persists up to 10 years following adalimumab OLE. No new safety findings were observed following longterm adalimumab treatment.

Is new drug prescribing in primary care specialist induced?

BACKGROUND: Medical specialists are often seen as the first prescribers of new drugs. However, the extent to which specialists influence new drug prescribing in primary care is largely unknown. METHODS: This study estimates the influence of medical specialists on new drug prescribing in primary care shortly after market introduction. The influence of medical specialists on prescribing of five new drugs was measured in a cohort of 103 GPs, working in 59 practices, over the period 1999 until 2003. The influence of medical specialists on new drug prescribing in primary care was assessed using three outcome measures. Firstly, the proportion of patients receiving their first prescription for a new or reference drug from a specialist. Secondly, the proportion of GPs prescribing new drugs before any specialist prescribes to their patients. Thirdly, we compared the time until the GP's first own prescribing between GPs who waited for prescriptions from specialists and those who did not. RESULTS: The influence of specialists showed considerable differences among the new drugs studied. The proportion of patients receiving their first prescription from a specialist was greatest for the combination salmeterol/fluticasone (60.2%), and lowest for rofecoxib (23.0%). The proportion of GPs prescribing new drugs before waiting for prescriptions from medical specialists ranged from 21.1% in the case of esomeprazole to 32.9% for rofecoxib. Prescribing new drugs by specialists did not shorten the GP's own time to prescribing. CONCLUSION: This study shows that the influence of medical specialists is clearly visible for all new drugs and often greater than for the existing older drugs, but the rapid uptake of new drugs in primary care does not seem specialist induced in all cases. GPs are responsible for a substantial amount of all early prescriptions for new drugs and for a subpopulation specialist endorsement is not a requisite to initiate in new drug prescribing. This contradicts with the idea that the diffusion of newly marketed drugs always follows a two-step model, with medical specialists as the innovators and GPs as the followers.

The effect of pharmacotherapy audit meetings on early new drug prescribing by general practitioners.

BACKGROUND: New drugs are cornerstones of clinical practice. However, when included in practice in an erratic fashion, there is valid concern about uncertain risk-benefit for patients and increased healthcare expenditures. In several countries, general practitioners (GPs) and pharmacists work closely together to ensure proper use of new drugs in clinical practice. OBJECTIVE: To estimate the effect of pharmacotherapy audit meetings (PTAMs) between GPs and community pharmacists on prescribing of newly marketed drugs by GPs. METHODS: We conducted an observational study of new drug prescribing in a cohort of 103 GPs, working in 59 practices, from 1999 until 2003. The main outcome measures were the decisions to start therapy with a new drug or with an existing older drug from the same therapeutic category within the first 6 months after market introduction. Multilevel modeling was used for analyses. RESULTS: Overall, in 6.1% of the decisions to start drug therapy, GPs chose the drug that was most recently introduced into the market. The GPs attending low-quality PTAMs made 1861 decisions to start therapy; in 112 (6.0%) of those decisions, a new drug was preferred over an older alternative. GPs participating in high-quality PTAMs preferred a new drug in only 3.4% of the 3138 decisions made. Compared with GPs participating in PTAMs on the highest quality level (level 4), GPS attending level 1 or level 2 PTAMs were more than twice as likely to start therapy with new drugs than with older drugs (OR 2.24; 95% CI 1.04 to 4.81 vs OR 2.31; 95% CI 1.30 to 4.09, respectively). CONCLUSIONS: PTAMs may be an effective way to control early prescribing of new drugs in general practice. For PTAMs to be effective, it is vital that GPs and pharmacists set common goals on how to optimize pharmacotherapy. This concordance should be reflected in PTAMs that result in concrete decisions with auditing of GP prescribing behavior. Pharmacists should play an active role in organizing PTAMs to increase their influence on drug prescribing.

Which pharmacists contribute to high-level pharmacotherapy audit meetings with general practitioners?

BACKGROUND: In the Netherlands, community pharmacists and general practitioners (GPs) collaborate in pharmacotherapy audit meetings (PTAMs) to optimize pharmacotherapy. OBJECTIVE: To identify associations between the quality level of PTAMs and characteristics of pharmacists. METHODS: We used a cross-sectional questionnaire design in a Dutch general practice and community pharmacy setting to estimate the contribution of pharmacists to the quality level of PTAMs. The questionnaire was sent to 123 community pharmacies working closely with 104 GP practices. The outcome variable was the quality level of PTAMs. The questionnaire provided information on 4 topics that were used as independent variables: characteristics of the PTAMs, provision of pharmacotherapy activities, characteristics of the pharmacists, and characteristics of the pharmacies. RESULTS: In total, 109 (88.6%) pharmacists completed the questionnaire, with 103 participating in 62 different PTAMs. Seventeen pharmacists participated in level 1 PTAMs (lowest level), 57 in level 2, 21 in level 3, and 8 in PTAMs at the highest level. The multinomial logistic regression identified only one significant association: pharmacists who participated in the highest quality level reported that they undertake initiatives in PTAMs (OR 2.98; 95% CI 1.07 to 8.26) more frequently compared with pharmacists participating on the lowest level. CONCLUSIONS: In light of existing evidence, the role of pharmacists in PTAMs seems to be important. Pharmacists should create a distinct profile of their expertise, allowing them to professionalize PTAMs by undertaking more initiatives. PTAMs offer pharmacists a great opportunity to become integral members of the prescribing process.

Linking community pharmacy dispensing data to prescribing data of general practitioners.

BACKGROUND: Databases are frequently used for pharmacoepidemiological research. However, most of these databases consist either of prescribing, dispensing or administrative data and therefore lack insight in the interaction between the several health professionals around the patient. METHODS: To determine the success rate of linking records from the dispensing database of the Foundation for Pharmaceutical Statistics to the prescribing database of the second Dutch national survey of general practice, conducted by NIVEL (Netherlands Institute for Health Services Research), a deterministic record linkage approach was used with patient and prescription characteristics as matching variables between the two databases. RESULTS: The catchment area included 123 community pharmacies, 90 GP practices and approximately 170,000 unique patients. Overall 110,102 (64.8%) unique patients were linked using the matching variables patient's gender, year of birth, the 4-digit part of the postal code, date of dispensing/prescribing and ATC-code. The final database contains of the 110,102 both prescribing data from 83 GP practices and dispensing data of 112 community pharmacies. CONCLUSION: This study shows that linkage of dispensing to prescribing data is feasible with a combination of patient characteristics, such as gender, year of birth and postal code, and prescription characteristics like prescription date and ATC-code. We obtained a linkage proportion of 64.8% resulting in complete prescribing and dispensing history of 110,102 patients. This offers an opportunity to gain insight in the mechanisms and factors influencing drug utilisation in general practice.

The trade-off between cardiovascular and gastrointestinal effects of rofecoxib.

BACKGROUND: The cyclooxygenase-2 (COX-2) inhibitor rofecoxib was registered in 1999. By 2000, the first reports were published indicating that the agent was possibly associated with an increased risk of myocardial infarction. Since then a surge of data supporting this association has become available. To interpret these data it is essential to ascertain the cardiovascular risk profile of users of rofecoxib relative to other non-steroidal anti-inflammatory drug (NSAID) recipients. OBJECTIVE: To assess differences in cardiovascular risk between starters of rofecoxib versus starters of any other NSAID. SETTING: Data sampled from a representative research network of Dutch general practitioners (GPs) in 2001. DESIGN: New users (starters) of rofecoxib were compared to starters of any other NSAID, unmatched and matched on age, gender, and indication nested in the cohort of the second Dutch National Survey of General Practice. RESULTS: A total of 40.4% of patients starting on rofecoxib had cardiovascular co-morbidity. Patients starting on rofecoxib were twice more likely to have a history of gastrointestinal (GI) morbidity, compared to patients starting on other NSAIDs (OR(adj) = 2.09; 95%CI = 1.65-2.66). These patients were also more likely to have cardiovascular co-morbidity (OR = 1.90; 95%CI = 1.60-2.24) compared to recipients of rofecoxib with no GI co-morbidity. Cardiovascular morbidity was present at the time of rofecoxib exposure in over 61% of carriers of a composite risk profile including age 60 years or older, GI co-morbidity and diagnosis of rheumatoid arthritis and osteoarthritis. CONCLUSIONS: In general, a typical recipient of an NSAID is aged and carrier of a serious cardiovascular risk profile. Selective prescribing of rofecoxib to provide claimed gastroprotection, indirectly and unintentionally resulted in prescribing rofecoxib in a population with high frequencies of cardiovascular morbidities.

Patient characteristics associated with prescribing of a newly introduced drug: the case of rofecoxib.

OBJECTIVE: To identify socio-demographic characteristics of the first patients receiving a new drug--rofecoxib. OUTCOME MEASUREMENT: Patients starting on rofecoxib or another non-steroidal anti-inflammatory drug (NSAID) and who had not received any NSAIDs the 90 days prior to starting. RESULTS: Starting on rofecoxib was associated with an increasing age (OR in age 80 years and older 8.7; 95% CI 6.7-11.2), a poor self-perceived health (OR=2.4; 95% CI 1.8-3.3), female gender (OR=1.4; 95% CI 1.2-1.6), private insurance (OR=1.3; 1.1-1.5) and previous acetaminophen use (OR=1.3; 1.1-1.7). CONCLUSION: This study noted that specific patient characteristics were associated with getting rofecoxib prescribed shortly after marketing. General practitioners should be aware of selectively prescribing new drugs to specific patients because it may place patients at unintentional and avoidable risk.