The early clinical course of infliximab treatment in rheumatoid arthritis: results from the REMARK observational study.

OBJECTIVES: We aimed to describe patterns of disease activity during infliximab plus methotrexate (MTX) treatment and explore C-reactive protein (CRP) as a potential marker of early response. METHODS: REMARK was a phase IV, open-label, observational study of infliximab-naïve adults with rheumatoid arthritis (RA) who received infliximab 3 mg/kg plus MTX for 14 weeks. Treatment response was evaluated in 3 subgroups: patients with <1 year disease duration who were TNF-inhibitor (TNFi)-naïve, patients with ≥ 1 year disease duration who were TNFi-naïve, and patients who had previous TNFi failure or intolerance. In post hoc analyses, CRP kinetic profiles were analysed by EULAR response (good, moderate, non-response) in REMARK and in an independent replication with data from the ASPIRE study. RESULTS: In the efficacy-evaluable population (n=662), median 28-joint disease activity score (DAS28) improved from baseline to Week 14 (5.2 vs. 3.6, p<0.0001). Regardless of disease history subgroup, most patients had good or moderate EULAR responses at Weeks 2 (64.9%), 6 (74.1%), and 14 (73.6%). DAS28 and its components did not differ across patient subgroups. Disease flare occurred in 16.2% of patients. CRP levels declined markedly at Week 2, but patients who were EULAR non-responders at Week 14 showed a CRP rebound at Weeks 6 and 14. This CRP pattern was independently replicated in data from ASPIRE. Adverse events were consistent with the known risk profile of infliximab. CONCLUSIONS: Infliximab plus MTX treatment in patients with RA rapidly diminished disease activity. A unique pattern of CRP rebound was found in non-responders early in treatment.

Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, Part 1.

OBJECTIVES: To assess whether combination therapy with infliximab (IFX) plus nonsteroidal anti-inflammatory drugs (NSAIDs) is superior to NSAID monotherapy for reaching Assessment of SpondyloArthritis international Society (ASAS) partial remission in patients with early, active axial spondyloarthritis (SpA) who were naïve to NSAIDs or received a submaximal dose of NSAIDs. METHODS: Patients were randomised (2 : 1 ratio) to receive naproxen (NPX) 1000 mg daily plus either IFX 5 mg/kg or placebo (PBO) at weeks 0, 2, 6, 12, 18 and 24. The primary efficacy measure was the percentage of patients who met ASAS partial remission criteria at week 28. Several other measures of disease activity, clinical symptoms and patient-rated outcomes were evaluated. Treatment group differences were analysed with Fisher exact tests or analysis of covariance. RESULTS: A greater percentage of patients achieved ASAS partial remission in the IFX+NPX group (61.9%; 65/105) than in the PBO+NPX group (35.3%; 18/51) at week 28 (p=0.002) and at all other visits (p<0.05, all comparisons). Results of most other disease activity and patient-reported endpoints (including Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, multiple quality of life measures and pain measures) showed greater improvement in the IFX+NPX group than the PBO+NPX group, with several measures demonstrating early and consistent improvement over 28 weeks of treatment. CONCLUSIONS: Patients with early, active axial SpA who received IFX+NPX combination treatment were twice as likely to achieve clinical remission as patients who received NPX alone. NPX alone led to clinical remission in a third of patients.

Maintenance of biologic-free remission with naproxen or no treatment in patients with early, active axial spondyloarthritis: results from a 6-month, randomised, open-label follow-up study, INFAST Part 2.

OBJECTIVE: To investigate whether biologic-free remission can be achieved in patients with early, active axial spondyloarthritis (SpA) who were in partial remission after 28 weeks of infliximab (IFX)+naproxen (NPX) or placebo (PBO)+NPX treatment and whether treatment with NPX was superior to no treatment to maintain disease control. METHOD: Infliximab as First-Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial (INFAST) Part 1 was a double-blind, randomised, controlled trial in biologic-naïve patients with early, active, moderate-to-severe axial SpA treated with either IFX 5 mg/kg+NPX 1000 mg/d or PBO+NPX 1000 mg/d for 28 weeks. Patients achieving Assessment of SpondyloArthritis international Society (ASAS) partial remission at week 28 continued to Part 2 and were randomised (1:1) to NPX or no treatment until week 52. Treatment group differences in ASAS partial remission and other efficacy variables were assessed through week 52 with Fisher exact tests. RESULTS: At week 52, similar percentages of patients in the NPX group (47.5%, 19/40) and the no-treatment group (40.0%, 16/40) maintained partial remission, p=0.65. Median duration of partial remission was 23 weeks in the NPX group and 12.6 weeks in the no-treatment group (p=0.38). Mean Bath Ankylosing Spondylitis Disease Activity Index scores were low at week 28, the start of follow-up treatment (NPX, 0.7; no treatment, 0.6), and remained low at week 52 (NPX, 1.2; no treatment, 1.7). CONCLUSIONS: In axial SpA patients who reached partial remission after treatment with either IFX+NPX or NPX alone, disease activity remained low, and about half of patients remained in remission during 6 months in which NPX was continued or all treatments were stopped.

Measuring joint involvement in polyarticular psoriatic arthritis: an introduction of alternatives.

OBJECTIVE: To compare the reliability of 3 different simplified joint counts with the gold standard 66 swollen/68 tender joint count (JC66/68) for assessing clinical response in patients with polyarticular psoriatic arthritis (PsA). METHODS: The 28-joint count (JC28), in the same way that it is used in rheumatoid arthritis, and 2 measures including distal interphalangeal (DIP) joints (the 32-joint count [JC32], including all finger joints as well as wrists and knees, and 36-joint count [JC36], which additionally included elbows and ankles), were compared with the JC66/68 in 182 patients using data from the Infliximab Multinational Psoriatic Arthritis Controlled Trial 2 trial database. Pearson's correlation coefficients were calculated to compare the swollen and tender JC28, JC32, and JC36 with the corresponding results of the total JC66/68. American College of Rheumatology (ACR) responses based on the individual measures were compared, and their ability in predicting a clinical response of ACR 20% improvement (ACR20) based on the JC66/68 was assessed by calculating the area under the receiver operating characteristic curve via logistic regression and the maximum Youden indices at weeks 14 and 24. RESULTS: All simplified joint counts were highly correlated to the standard JC66/68 both for tenderness and swelling at each individual visit (Pearson's correlation coefficients consistently >0.8, n = 182-200; P < 0.0001). Logistic regression for ACR20 response showed that area under the curve was constantly >0.91, with comparable results for Youden indices of the simplified joint counts. CONCLUSION: All simplified joint counts considered seemed sufficiently sensitive and specific to measure clinical response in trial patients with polyarticular PsA when compared with the JC66/68, no matter whether DIP joints were included (the JC36 and JC32) or excluded (the JC28). Further research will be needed to clarify this issue.

Classification models for disease: the effect of associations between markers on calculating the risk for disease by likelihood ratio products.

OBJECTIVES: The risk for disease or a bad prognosis can be calculated by means of prediction or classification models that take into account multiple variables. Different methods exist to construct such models. Some of those methods, including the likelihood ratio (LR) product method neglect dependency between variables. We aimed to evaluate the effect of neglecting dependency between variables in prediction or classification models. PATIENTS AND METHODS: Population I consisted of 1003 consecutive patients with a new diagnostic problem for which RA was included in the differential diagnosis and final diagnoses (RA or non-RA) were established after 1 year. The baseline variables included in the model are rheumatoid factor, anti-citrullinated protein/peptide antibodies and the HLA-shared epitope. Population II consisted of 847 patients with definite ankylosing spondylitis (AS). Six variables (psoriasis, inflammatory bowel disease, uveitis, HLA-B27 status and latest available CRP) were evaluated. Here, specificities of the features were derived from literature and different scenarios of association between variables in controls and diseased are estimated. RESULTS: When two features are similarly associated in cases and controls, risks for disease will be overestimated by neglecting dependency between variables. In the presented datasets, this resulted in a up to 12% overestimation of the risk. CONCLUSIONS: We showed how the height of over- or underestimation of risks can be evaluated when dependencies between two variables are neglected. This is important to evaluate the predictive value of combinations of features in cases where no data are available on associations in controls.

Classification and management of allergic rhinitis patients in general practice during pollen season.

BACKGROUND: Allergic rhinitis (AR) represents a major challenge in primary care. The Allergic Rhinitis and its Impact on Asthma (ARIA) group proposed a new classification for AR and developed evidence-based guidelines for the management of this disease. We conducted this study to further characterize the classes of AR described by ARIA, and to evaluate whether the management of AR in general practice is in accordance with the ARIA guidelines. METHODS: During the pollen season of 2003, 95 Belgian general practitioners (GPs) enrolled 804 patients who presented with symptoms of AR. For each patient, a questionnaire comprising the clinical presentation and management was completed. RESULTS: In 64% of the patients, AR was classified as intermittent and in 36% as persistent. Persistent rhinitis caused more discomfort than intermittent rhinitis. Only 50% of the patients had ever undergone allergy testing. Among them, 51% were allergic to both seasonal and perennial allergens. Eighty-two per cent of the persistent rhinitics were allergic to at least one seasonal allergen and 72% of the intermittent rhinitics to at least one perennial allergen. When compared strictly with the ARIA recommendations, 49% of the patients with mild and/or intermittent AR were overtreated, whereas about 30% of those with moderate/severe persistent rhinitis were undertreated. CONCLUSION: This study confirms that the previous classification of AR into 'seasonal' and 'perennial' is not satisfactory and that intermittent and persistent AR are not equivalent to seasonal and perennial AR respectively. Furthermore, persistent rhinitis has been shown to be a distinct disease entity. Further efforts are required to disseminate and implement evidence-based diagnostic and treatment guidelines for AR in primary care practice.

Desloratadine 5 mg once daily improves the quality of life of patients with chronic idiopathic urticaria.

BACKGROUND: Chronic urticaria is known to debilitate a person's quality of life via sleep disruption, itching lesions, fatigue, social isolation, energy loss and emotional/sexual difficulties. Once-daily desloratadine significantly improved the signs and symptoms of CIU. OBJECTIVE: Assess the effect of desloratadine 5 mg once daily on the quality of life of patients suffering of chronic idiopathic urticaria (CIU). Study population One-hundred twenty-one consecutive patients with CIU present for at least 6 weeks prior to inclusion and with a current flare of at least 3 weeks, were included in the study in 24 Belgian centres. RESULTS: The mean dermatology life quality index (DLQI) significantly decreased from baseline to day 7 and further to day 42. Sixty per cent and 77% of patients had a clinically significant change (i.e. a decrease of at least 2 points) at day 7 or day 42, respectively, as compared with that of day 0. Change in pruritus and size of the hives significantly correlated with the change in the score of the quality of life. One-third of patients experienced complete relief whereas in 1 of 10 patients no effect was experienced. CONCLUSIONS: Desloratadine significantly improves the quality of life of patients with chronic idiopathic urticaria as reflected by the dermatology life quality index (DLQI).

A dose adjustment in patients with rheumatoid arthritis not optimally responding to a standard dose of infliximab of 3 mg/kg every 8 weeks can be effective: a Belgian prospective study.

OBJECTIVES: To analyse the effect of a dose increase in patients with severe rheumatoid arthritis (RA) with insufficient clinical response to 3 mg/kg infliximab every 8 weeks. METHODS: Patients suffering from active refractory RA despite methotrexate, were treated with i.v. infusions of infliximab (3 mg/kg) on week 0, 2, 6 and every 8 weeks thereafter. Based on the clinical judgement at week 22, patients received a dose increase of 100 mg from week 30 on. The American College of Rheumatology (ACR) core set for disease activity measures was regularly assessed. RESULTS: Five hundred and eleven RA patients were included. At week 22, 61.4, 34 and 14.1% of all patients met ACR 20, ACR 50 and ACR 70 criteria, respectively, and 6.1% of patients were in remission. A low swollen joint count at baseline was correlated with improvement at week 22 for ACR 20 (P < 0.06), ACR 50 (P < 0.06) and ACR 70 (P < 0.005). The change in HAQ score between weeks 0 and 22 was predictive for response at week 54 (P < 0.01). The dose of infliximab was increased by 100 mg in 22% of the patients. Most baseline values of patients requiring dose increase were higher (P < or = 0.001) than the baseline values of the remaining patients. Increasing the dose of infliximab by one vial from week 30 on could circumvent the partial loss of response in these patients. CONCLUSION: Infliximab use in this large out-patient cohort resulted in a significant clinical improvement. A subgroup that partially lost response during the first 22 weeks could regain response by adding 100 mg of infliximab to the subsequent doses. Due to the current study design, however, a regression to the mean like effect could not be ruled out.