Achieving minimal disease activity in psoriatic arthritis predicts meaningful improvements in patients’ health-related quality of life and productivity

Background Although psoriatic arthritis is complex and involves multiple domains, recent advances in treatments have made remission or near-remission of most symptoms a potentially achievable goal for many patients. We sought to evaluate whether achieving minimal disease activity (MDA) criteria represented meaningful improvement from the patient perspective. Methods Data were combined from two randomized, multinational, 24 week clinical studies of ixekizumab, a high-affinity monoclonal antibody selectively targeting interleukin-17A, in biological drug-naïve or experienced adults. MDA required 5 of 7 of: tender joint count ≤1; swollen joint count ≤1; Psoriasis Area and Severity Index total score ≤ 1 or body surface area ≤ 3%; patient’s assessment of pain visual analogue scale (VAS) ≤15; patient’s global assessment of disease activity VAS ≤20; Health Assessment Questionnaire Disability Index ≤0.5; and tender entheseal points ≤ 1. MDA responders and non-responders were compared for mean change from baseline on the 36-Item Short Form Health Survey (SF-36), European Quality of Life 5 Dimension 5 Level Health Questionnaire (EQ-5D-5 L); EQ-5D-5 L VAS; and Work Productivity and Activity Impairment–Specific Health Problem (WPAI-SHP) questionnaire. Results MDA responders had significantly greater improvements versus non-responders in each SF-36 domain and in the SF-36 physical summary score; improvements were also greater in the EQ-5D-5 L and EQ-5D-5 L VAS, and in 3 of the 4 WPAI-SHP domains. MDA responders were more likely to achieve minimal clinically important differences than non-responders. Conclusion These findings support MDA response as being strongly associated with achieving improved disease status based on measures of patient reported health-related quality of life and productivity. Trial registration SPIRIT-P1, NCT01695239, First Posted: September 27, 2012; and SPIRIT-P2, NCT02349295, First Posted: January 28, 2015

Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies

Background Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. Method Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3–6) to full resolution (FR), stable (similar or reduction of EC), or worse (EC > baseline). Efficacy outcomes (ACR, PASI, HAQ-DI, SF-36 PCS, and DAS28-CRP) were assessed in patients with or without baseline enthesitis. Results are reported for secukinumab 300 and 150 mg in the overall population and by prior TNFi treatment. Results A total of 65% (466/712) of patients had baseline enthesitis. In the overall population, FR was achieved as early as week 16 in 65% (300 mg) and 56% (150 mg) versus 44% (placebo) patients, with further improvements to 91% (300 mg) and 88% (150 mg) at week 104. The majority (89%) of patients without enthesitis at baseline maintained this status at week 104. Median days to resolution of EC were shorter with secukinumab 300 and 150 mg versus placebo (57 and 85 vs 167 days, respectively). In patients with EC of 1 or 2, shift analysis from baseline to week 24 showed that more patients achieved FR with secukinumab 300 mg and 150 mg versus placebo, whereas no difference between secukinumab and placebo was shown in the more severe patients with EC of 3–6. Increases in proportions of patients with FR were observed with secukinumab irrespective of the severity of EC from baseline to week 104. Improvements in efficacy outcomes were similar in patients with or without enthesitis treated with secukinumab 300 mg. Conclusion Secukinumab provided early and sustained resolution of enthesitis in patients with PsA over 2 years. Secukinumab 300 mg provided higher resolution than 150 mg in patients with more severe baseline EC and showed similar overall efficacy in patients with or without enthesitis. Trial registration FUTURE 2: ClinicalTrials.gov, NCT01752634 (date of study registration: December 19, 2012), and EudraCT, 2012-004439-22 (date of study registration: December 12, 2012) FUTURE 3: ClinicalTrials.gov, NCT01989468 (date of study registration: November 21, 2013), and EudraCT, 2013-004002-25 (date of study registration: December 17, 2013

Impact of guselkumab, an interleukin-23 p19 subunit inhibitor, on enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis: results from a randomised, placebo-controlled, phase II study

Objective To evaluate the effect of guselkumab on enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA). Methods This was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0–3 on each digit; enthesitis was assessed using the Leeds Enthesitis Index (0–6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses. Results Of 149 randomised patients, 107 patients had enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of enthesitis and dactylitis. At week 56, mean improvements in enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in enthesitis and dactylitis versus non-responders (week 24). Conclusions At week 24, the guselkumab group had greater mean improvements in enthesitis and dactylitis and greater proportions of patients with resolution of enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in enthesitis and dactylitis

Trazodone plus pregabalin combination in the treatment of fibromyalgia: a two-phase, 24-week, open-label uncontrolled study

<p>Abstract</p> <p>Background</p> <p>Although trazodone is frequently used by fibromyalgia patients, its efficacy on this disease has not been adequately studied. If effective, pregabalin, whose beneficial effects on pain and sleep quality in fibromyalgia have been demonstrated, could complement the antidepressant and anxiolytic effects of trazodone. The aim of the present study was to assess the effectiveness of trazodone alone and in combination with pregabalin in the treatment of fibromyalgia.</p> <p>Methods</p> <p>This was an open-label uncontrolled study. Trazodone, flexibly dosed (50-300 mg/day), was administered to 66 fibromyalgia patients during 12 weeks; 41 patients who completed the treatment accepted to receive pregabalin, also flexibly dosed (75-450 mg/day), added to trazodone treatment for an additional 12-week period. Outcome measures included the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI), the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS), the Brief Pain Inventory (BPI), the Short-Form Health Survey (SF-36), and the Patients' Global Improvement scale (PGI). Emergent adverse reactions were recorded. Data were analyzed with repeated measures one-way ANOVA and paired Student's t test.</p> <p>Results</p> <p>Treatment with trazodone significantly improved global fibromyalgia severity, sleep quality, and depression, as well as pain interference with daily activities although without showing a direct effect on bodily pain. After pregabalin combination additional and significant improvements were seen on fibromyalgia severity, depression and pain interference with daily activities, and a decrease in bodily pain was also apparent. During the second phase of the study, only two patients dropped out due to side effects.</p> <p>Conclusions</p> <p>Trazodone significantly improved fibromyalgia severity and associated symptomatology. Its combination with pregabalin potentiated this improvement and the tolerability of the drugs in association was good.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00791739">NCT00791739</a></p

Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase III Trial

Objective: To examine the efficacy of methotrexate monotherapy relative to etanercept monotherapy and the value of combining methotrexate and etanercept for the treatment of patients with psoriatic arthritis (PsA). Methods: In this double‐blind study, 851 patients with PsA were randomized to 1 of 3 treatment arms, as follows: oral methotrexate (20 mg) plus subcutaneous placebo given weekly (n = 284), subcutaneous etanercept (50 mg) plus oral placebo given weekly (n = 284), or subcutaneous etanercept (50 mg) plus oral methotrexate (20 mg) given weekly (combination therapy; n = 283). The American College of Rheumatology 20% improvement (ACR20) response and Minimal Disease Activity (MDA) response at week 24 were the primary end point and key secondary end point, respectively. Other measures of inflammatory arthritis, radiographic progression, and nonarticular disease manifestations were also assessed. Results: Patients with PsA had a mean ± SD age of 48.4 ± 13.1 years, and the mean ± SD duration of PsA was 3.2 ± 6.3 years (median 0.6 years). ACR20 and MDA response rates at week 24 were significantly greater in patients who received etanercept monotherapy compared with those who received methotrexate monotherapy (ACR20, 60.9% versus 50.7% of patients [P = 0.029]; MDA, 35.9% versus 22.9% of patients [P = 0.005]), and both were significantly greater in the combination therapy group compared with the methotrexate monotherapy group at week 24 (ACR20, 65.0% versus 50.7% of patients [P = 0.005]; MDA, 35.7% versus 22.9% of patients [P = 0.005]). Other secondary outcomes (ACR50 and ACR70 response rates, proportions of patients achieving a Very Low Disease Activity score, and PsA disease activity scores) showed between‐group differences that were consistent with the primary and key secondary end point results. Furthermore, patients in both etanercept treatment arms showed less radiographic progression at week 48 compared with patients who received methotrexate monotherapy. Outcomes were similar in the combination therapy and etanercept monotherapy groups, except for some skin end points. No new safety signals were seen. Conclusion: Etanercept monotherapy and combination therapy with etanercept and methotrexate showed greater efficacy than methotrexate monotherapy in patients with PsA, according to the ACR and MDA response rates and extent of radiographic progression at follow‐up. Overall, combining methotrexate and etanercept did not improve the efficacy of etanercept

The use of tumour necrosis factor alpha-blockers in daily routine. An Austrian consensus project

To define relevant disease parameters and their respective limits indicating the initiation of TNF-α-blockers in individual patients. Subsequently, to analyze retrospectively patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS), who started TNF-α inhibition in 2006. Points to consider, regarded relevant for individual treatment decisions as well as their assessment methods, were ascertained by experts’ consensus applying the Delphi technique. Subsequently, these parameters’ thresholds with respect to the initiation of a TNF-α-blocker were identified. Thereafter, the rheumatologists representing 12 centres all over Austria agreed to retrospectively analyze their patients started on a TNF-α-blocker in 2006. Experts’ opinion regarding disease parameters relevant to initiate TNF-α-blockers in RA patients only slightly differed from those applied in clinical trials, but the parameters’ threshold values were considerably lower. For PsA patients, some differences and for AS patients, considerable differences between experts’ opinion and clinical studies appeared, which held also true for decisive parameters’ means and thresholds. Six hundred and fifty patients, started on TNF-blockers in 2006, could be analyzed retrospectively, 408 RA patients (53.3 years mean, 340 females), 93 PsA patients (48.9 years mean, 59 males) and 149 AS patients AS (42.2 years mean, 108 males), representing approximately 25% of all Austrian patients initiated on a TNF-blocker in this respective year. Far more individualized, patient-oriented treatment approaches, at least in part, are applied in daily routine compared with those derived from clinical trials or recommendations from investigative rheumatologists

Identification of symptom and functional domains that fibromyalgia patients would like to see improved: a cluster analysis

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to determine whether some of the clinical features of fibromyalgia (FM) that patients would like to see improved aggregate into definable clusters.</p> <p>Methods</p> <p>Seven hundred and eighty-eight patients with clinically confirmed FM and baseline pain ≥40 mm on a 100 mm visual analogue scale ranked 5 FM clinical features that the subjects would most like to see improved after treatment (one for each priority quintile) from a list of 20 developed during focus groups. For each subject, clinical features were transformed into vectors with rankings assigned values 1-5 (lowest to highest ranking). Logistic analysis was used to create a distance matrix and hierarchical cluster analysis was applied to identify cluster structure. The frequency of cluster selection was determined, and cluster importance was ranked using cluster scores derived from rankings of the clinical features. Multidimensional scaling was used to visualize and conceptualize cluster relationships.</p> <p>Results</p> <p>Six clinical features clusters were identified and named based on their key characteristics. In order of selection frequency, the clusters were Pain (90%; 4 clinical features), Fatigue (89%; 4 clinical features), Domestic (42%; 4 clinical features), Impairment (29%; 3 functions), Affective (21%; 3 clinical features), and Social (9%; 2 functional). The "Pain Cluster" was ranked of greatest importance by 54% of subjects, followed by Fatigue, which was given the highest ranking by 28% of subjects. Multidimensional scaling mapped these clusters to two dimensions: Status (bounded by Physical and Emotional domains), and Setting (bounded by Individual and Group interactions).</p> <p>Conclusion</p> <p>Common clinical features of FM could be grouped into 6 clusters (Pain, Fatigue, Domestic, Impairment, Affective, and Social) based on patient perception of relevance to treatment. Furthermore, these 6 clusters could be charted in the 2 dimensions of Status and Setting, thus providing a unique perspective for interpretation of FM symptomatology.</p

The GOLMePsA study protocol: an investigator-initiated, double-blind, parallel-group, randomised, controlled trial of GOLimumab and methotrexate versus methotrexate in early diagnosed psoriatic arthritis using clinical and whole body MRI outcomes

Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis which impacts significantly on the quality of life and work capacity of affected individuals. Recent evidence has shown that early control of inflammation in PsA leads to improved long-term outcomes. It is postulated that prompt intervention after diagnosis using a remission-induction treatment strategy will lead to improved outcomes and optimal disease control of PsA. The aim of the present study was to compare the clinical efficacy of a treatment strategy in newly diagnosed, treatment naïve PsA subjects, using the combination of golimumab (GOL), methotrexate (MTX) and steroids versus standard care (MTX monotherapy plus steroids). Methods/design: GOLMePsA is an investigator initiated, phase IIIb, single-centre, randomised, double-blind, placebo-controlled, two-armed, parallel-group, imaging-supplemented study. Eighty-eight PsA patients, diagnosed within 24 months prior to screening and treatment naïve, will be randomised at baseline to receive: (arm 1) the combination of intramuscular/intra-articular prednisolone, MTX and GOL or (arm 2) the combination of intramuscular/intra-articular prednisolone, MTX and placebo for 24 weeks (interventional period). Primary outcome measure is clinical improvement (at least 1 unit difference) in the Psoriatic ArthritiS Disease Activity Score (PASDAS) composite index. Reflecting a “step down” therapeutic approach, all participants successfully completing the interventional period will be followed up for a further 28 weeks. During this observational period, stable maintenance MTX monotherapy will continue for both arms, unless in case of intolerance or PsA relapse. In the latter case, additional treatment will be provided. Overall, the GOLMePsA study length is planned to be 52 weeks. Discussion: The hypothesis underlining this study is that very early treatment with first-line GOL reduces disease activity in PsA, in comparison to conventional therapy. Trial registration: EudraCT 2013–004122-28. 24/09/2013