Association between baseline cardiovascular risk and incidence rates of major adverse cardiovascular events and malignancies in patients with psoriatic arthritis and psoriasis receiving tofacitinib.

Background: Tofacitinib is a Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA) and has been investigated for psoriasis (PsO). Objectives: This post hoc analysis examined baseline cardiovascular (CV) disease risk and its association with the occurrence of major adverse cardiovascular events (MACE) and malignancies in tofacitinib-treated patients with PsA and PsO. Design: Included three phase III/long-term extension (LTE) PsA trials and seven phase II/phase III/LTE PsO trials of patients receiving ⩾ 1 dose of tofacitinib. Methods: Incidence rates (IRs: patients with events/100 patient-years) for MACE and malignancies (excluding non-melanoma skin cancer) were determined in subgroups according to history of atherosclerotic CV disease (ASCVD), baseline 10-year risk of ASCVD (in patients without history of ASCVD), and baseline metabolic syndrome (MetS). Results: For patients with PsA (N = 783) and PsO (N = 3663), respectively, tofacitinib exposure was 2038 and 8950 patient-years (median duration: 3.0 and 2.4 years), and 40.9% and 32.7% had MetS. Excluding missing CV risk profile data, 51/773 (6.6%) and 144/3629 (4.0%) patients had history of ASCVD, and in patients without history of ASCVD, around 20.0% had intermediate/high baseline 10-year ASCVD risk. For PsA and PsO, IRs of MACE were greatest in those with history of ASCVD or high baseline 10-year ASCVD risk. For PsA, five of six patients with MACE had baseline MetS. Malignancy IRs in patients with PsA were greatest in those with intermediate/high baseline 10-year ASCVD risk. Of these, eight of nine patients with malignancies had baseline MetS. In the PsO cohort, IR of malignancies was notably greater with high versus low/borderline/intermediate baseline 10-year ASCVD risk. Conclusion: In tofacitinib-treated patients with PsA/PsO, increased ASCVD risk and baseline MetS were associated with higher IRs for MACE and malignancies. Our results support assessing CV risk in patients with PsA/PsO and suggest enhanced cancer monitoring in those with increased ASCVD risk. Registration ClinicalTrialsgov: NCT01877668/NCT01882439/NCT01976364/NCT00678210/NCT01710046/NCT01241591/NCT01186744/NCT01276639/NCT01309737/NCT01163253. Plain Language Summary: People who have psoriatic arthritis or psoriasis may have more heart-related problems and cancer if they have a higher risk of cardiovascular disease: A study in people with psoriatic arthritis or psoriasis receiving tofacitinib Why was this study done? • People with psoriatic arthritis (PsA) and psoriasis (PsO) are more likely than the general population to have a disease affecting the heart and blood vessels [cardiovascular (CV) disease].• People who are more likely to have CV disease may also be more likely to have certain types of cancer.• Tofacitinib is a medicine to treat people with PsA and has been tested in people with PsO.• We wanted to know if the risk of CV disease affects the number of heart-related problems (including heart attack, stroke, or death) and cancer in people with PsA and PsO. What did the researchers do? • We used results from 10 clinical trials.• In these trials, people with PsA and PsO were taking tofacitinib 5 or 10 mg twice a day.• After the trials had ended, we measured people's risk of CV disease using a risk calculator. This risk calculator showed if they had a low, borderline, intermediate, or high risk of CV disease over the next 10 years. We also checked if they had had CV disease before treatment.• We checked if people had a group of conditions linked to CV disease: diabetes, high blood pressure, and obesity.• We counted the cases of heart-related problems and cancer in people once they started taking tofacitinib. What did the researchers find? In people with PsA and PsO taking tofacitinib:• There were more cases of heart-related problems and cancer in people who had intermediate or high risk of CV disease.• There were more cases of heart-related problems in people who had had CV disease before.• More people with diabetes, high blood pressure, and obesity had heart-related problems and cancer than people without those conditions. What do the findings mean? • It is important to measure risk and assess history of CV disease in people with PsA and PsO, including those taking tofacitinib.• We should test for cancer in people with high risk of CV disease.

Comorbidities, pain and fatigue in psoriatic arthritis, psoriasis and healthy controls: a clinical cohort study.

OBJECTIVES: To explore the prognostic value of pre-specified comorbidities on treatment outcomes in PsA, and to compare baseline data with cutaneous psoriasis without arthritis and healthy controls (HC). METHODS: Patients initiating conventional synthetic/biological disease-modifying antirheumatic drugs were enrolled in this clinical observational cohort study, and data on comorbidities, and clinical and patient-reported outcomes were retrieved at baseline and after 4 months. Pearson's chi-squared tests were performed to investigate the prognostic value of pre-specified comorbidities and achievement of ACR20, DAPSA50 and MDA. Mann-Whitney U tests were used to compare OMERACT PsA Core Outcome Set (COS) measures at baseline and follow-up for the pre-specified comorbidities. RESULTS: A total of 100 PsA patients were included at baseline. Statistically significantly fewer patients with obesity achieved DAPSA50 compared with patients without obesity (P =0.035), and fewer patients with hypertension (P =0.034) and Charlson Comorbidity Index (CCI) ≥1 (P =0.027), respectively, achieved MDA compared with patients without these comorbidities. Patients with obesity, hypertension, widespread pain, and CCI ≥1 had significantly worse COS measures at follow-up compared with patients without these comorbidities. At baseline, patients with PsA had higher disease burden compared with patients with cutaneous psoriasis and HC, including higher pain (P <0.001) and fatigue (P <0.001) scores, and more widespread pain (P =0.002). CONCLUSION: Obesity, hypertension and CCI ≥1 were prognostic factors for poorer treatment outcome rates in PsA. Pain and fatigue were more frequently reported among patients with PsA compared with patients with cutaneous psoriasis and HC. TRIAL REGISTRATION: The Danish National Committee on Health Research Ethics: H-15009080; Data Protection Agency: 2012-58-0004; ClinicalTrials.gov: NCT02572700.

A pilot study examining patient preference and satisfaction for ava®, a reusable electronic injection device to administer certolizumab pegol.

Background: Anti-tumor necrosis factor (anti-TNF) adherence is suboptimal. ava®, a reusable electromechanical self-injection device (e-Device) developed for certolizumab pegol (CZP) administration, aims to overcome some barriers to increase adherence. This study evaluates patient experience of the e-Device and its training materials and determines patient device preference.Methods: CZP-treated patients were recruited from the Netherlands, Denmark and Sweden. Patients completed a pre-injection Assessment of Self-Injection (ASI) questionnaire investigating self-injection perception. After training, patients administered 3 consecutive self-injections using the e-Device, patient experience of each was assessed using the post-injection ASI. An additional questionnaire evaluated training materials. After Injection 3, patients indicated their preference: the e-Device or their previous device.Results: 59 patients participated; most rated the e-Device highly for satisfaction, self-confidence and ease of use. The (negative) feelings and pain and skin reactions domains had low ratings. Post-injection ASI domain scores were similar following each of the 3 e-Device injections. Training materials were rated highly (video: 8.4/10; step-by-step guide: 8.4/10). 57.1% (32/56) patients preferred the e-Device over their previous self-injection device.Conclusions: Patients were satisfied with the e-Device and most preferred it over other self-injection devices. By improving patient experience, the e-Device may help increase medication adherence.

Risk of medical complications following total hip or knee arthroplasty in patients with rheumatoid arthritis: A register-based cohort study from Denmark.

OBJECTIVE: To investigate the risk of medical complications following total hip and knee arthroplasty (THA/TKA) among rheumatoid arthritis (RA) compared with osteoarthritis (OA) patients; and, to assess the risk of complications among biologics-treated RA patients. METHODS: In a nationwide register-based study, patients with RA and OA with THA/TKA surgery between 2000 and 2015 were identified and followed up to 90 days after surgery for venous thromboembolism (VTE), myocardial infarction and stroke, and non-surgical infections, respectively. Information on treatment with biologics was obtained in the DANBIO rheumatology register to compare risks of complications with non-biologics treated. RESULTS: A total of 2899 and 112,571 patients with RA and OA had THA/TKA. RA was associated with a hazard ratio (HR) of 1.29 (1.03 to 1.61) for infection following THA/TKA, but a HR of 0.60 (0.26 to 0.98) for VTE following TKA. Biologics treated patients had a HR of 1.35 (0.65 to 2.80) for infection and 4.82 (1.67 to 13.90) for VTE compared with non-biologics treated RA patients. RA patients had no increased risk of post-surgical myocardial infarction and stroke (HR 1.16, 0.76 to 1.78) compared with OA, but a higher incidence proportion was observed in biologics treated compared with non-biologics treated (1.0% vs 0.6%); however, the number of events were too small to estimate a HR. CONCLUSION: In this study, RA was a risk factor for infection after THA/TKA, and RA patients treated with biologics had a slightly increased risk compared with non-biologics treated RA patients. Compared with OA, RA patients had a lower risk of VTE following THA/TKA, but our finding of increased incidences of VTE in biologics-treated patients warrants further studies.

A portfolio of biologic self-injection devices in rheumatology: how patient involvement in device design can improve treatment experience.

Biologic drugs (e.g. anti-tumor necrosis factors) are effective treatments for multiple chronic inflammatory diseases including rheumatoid arthritis, axial spondyloarthritis, and psoriatic arthritis. Administration of biologic drugs is usually via subcutaneous self-injection, which provides many patient benefits compared to infusions including increased flexibility, reduced costs, and reduced caregiver burden. However, it is also associated with challenges such as needle phobia, patient treatment misconceptions and incorrect drug administration, and can be impacted by dexterity problems. Evidence suggests these problems, along with other drug administration challenges (e.g. patient forgetfulness, busy lifestyles, and polypharmacy), can reduce patient adherence to treatment. To combat these challenges, patient feedback has been used to develop a range of self-injection devices, including pre-filled syringes, pre-filled pens, and electronic injection devices. Providing different devices for drug administration gives patients the opportunity to choose a device that addresses the challenges they face as an individual. Research suggests involving patients in medical device development, providing patients with a choice of devices and enrolling individuals in patient support programs can empower patients to take control of their treatment journey. By providing a portfolio of self-injection devices, designed based on patient needs, patient experience will improve, potentially improving adherence and hence, long-term treatment outcomes.

Trial Characteristics as Contextual Factors When Evaluating Targeted Therapies in Patients With Psoriatic Disease: A Meta-Epidemiologic Study.

OBJECTIVE: To assess the importance of trial characteristics as contextual factors when evaluating the treatment effect of targeted therapies for patients with psoriatic disease. METHODS: We identified randomized controlled trials (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the 2 psoriatic conditions combined by using drug retention as a common outcome, and separately by using the American College of Rheumatology 20% improvement criteria (ACR20) for PsA and the Psoriasis Area Severity Index 75% improvement score (PASI75) for psoriasis. We explored potential effect modification of trial characteristics in stratified and meta-regression analyses. Odds ratios (ORs) were calculated and compared among the trial eligibility criteria via the ratio of ORs. RESULTS: Forty-eight PsA and psoriasis trials (51 comparisons; 17,737 patients) were eligible. Overall retention was OR 2.16 (95% confidence interval [95% CI] 1.70-2.75) with higher odds for PsA trials compared with psoriasis trials (ratio of ORs 2.55 [95% CI 1.64-3.97]). The eligibility criteria "targeted therapy history," "minimum required disease duration," "required negative rheumatoid factor," and "required Classification Criteria for Psoriatic Arthritis criteria" were of importance for achieving ACR20 in PsA. The eligibility criterion "minimum required disease duration" was of importance for achieving PASI75 in psoriasis. A total of 7 PsA trials had rescue before time-point-of-retention reporting (adaptive trials). CONCLUSION: From this exploratory meta-epidemiologic study, we now have evidence from RCTs to support the notion that patients with PsA are more likely to adhere to targeted therapies compared to patients with psoriasis. Furthermore, we identified a few contextual factors of importance in regard to achieving ACR20 in PsA trials and PASI75 in psoriasis trials.

A systematic review of measurement properties of patient reported outcome measures in psoriatic arthritis: A GRAPPA-OMERACT initiative.

BACKGROUND: An updated psoriatic arthritis (PsA) core outcome set (COS) for randomized controlled trials (RCTs) was endorsed at the Outcome Measures in Rheumatology (OMERACT) meeting in 2016. OBJECTIVES: To synthesize the evidence on measurement properties of patient reported outcome measures (PROMs) for PsA and thereby contribute to development of a PsA core outcome measurement set (COMS) as described by the OMERACT Filter 2.0. METHODS: A systematic literature search was performed in EMBASE, MEDLINE and PsycINFO on Jan 1, 2017 to identify full-text articles with an aim of assessing the measurement properties of PROMs in PsA. Two independent reviewers rated the quality of studies using the COnsensus based standards for the Selection of health Measurement INstruments (COSMIN) checklist, and performed a qualitative evidence synthesis. RESULTS: Fifty-five studies were included in the systematic review. Forty-four instruments and a total of 89 scales were analyzed. PROMs measuring COS domains with at least fair quality evidence for good validity and reliability (and no evidence for poor properties) included the Stockerau Activity Score for PsA (German), Psoriasis Symptom Inventory, visual analogue scale for Patient Global, 36 Item Short Form Health Survey Physical Function subscale, Health Assessment Questionnaire Disability Index, Bath Ankylosing Spondylitis Functional Index, PsA Impact of Disease questionnaire, PsA Quality of Life questionnaire, VITACORA-19, Functional Assessment of Chronic Illness Therapy Fatigue scale and Social Role Participation Questionnaire. CONCLUSIONS: At least one PROM with some evidence for aspects of validity and reliability was available for six of the eight mandatory domains of the PsA COS.

Th17 Inhibitors in Active Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.

BACKGROUND: Several biologics targeting the Th17 pathway have been developed for the treatment of psoriatic arthritis (PsA), a disabling disease with moderate response and an increased incidence of serious infections to first-line biologics (TNF-α antagonists). Th17 inhibitors could replace TNF-α antagonists as first-line biologic agents. We determined the overall treatment effect of Th17 pathway inhibitors compared to placebo or active control on American College of Rheumatology (ACR) 20 response at week 12 (primary objective), risk of infections, discontinuation of treatment due to adverse events, and serious adverse events during the placebo-controlled period (12-24 weeks) in adults with active PsA in published randomized controlled trials. METHODS: The SCOPUS database was searched. The Cochrane risk of bias tool was used for assessing quality. The pooled relative risk (RR) was derived from random effects models. RESULTS: Seven randomized controlled trials were included which randomized 1,718 patients to Th17 inhibitors and 840 to placebo. Patients treated with Th17 inhibitors had an RR of 2.04 (95% CI: 1.79-2.33; p < 0.001) for achieving an ACR20 response at week 12 (I2 = 0%; p = 0.89) compared to placebo-treated patients. There was no evidence of publication bias. The result was consistent for study phase and outcome (ACR50/70), mechanism of action and TNF-α naivety. RR of infections was 1.06 (0.91-1.23), that of candida infections was 3.35 (0.75-14.95), that of serious adverse events was 0.82 (0.42-1.59) and that of discontinuation of treatment was 0.54 (0.31-0.93) among treated versus placebo subjects. No incident cases of tuberculosis were reported. CONCLUSION: In patients with active PsA, biologics targeting the Th17 axis produce a clinically significant improvement in joint disease activity with acceptable safety and tolerability for short-term treatment compared to placebo.

Weight loss for overweight and obese individuals with gout: a systematic review of longitudinal studies.

OBJECTIVES: Weight loss is commonly recommended for gout, but the magnitude of the effect has not been evaluated in a systematic review. The aim of this systematic review was to determine benefits and harms associated with weight loss in overweight and obese patients with gout. METHODS: We searched six databases for longitudinal studies, reporting the effect of weight loss in overweight/obese gout patients. Risk of bias was assessed using the tool Risk of Bias in Non-Randomised Studies of Interventions. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation. RESULTS: From 3991 potentially eligible studies, 10 were included (including one randomised trial). Interventions included diet with/without physical activity, bariatric surgery, diuretics, metformin or no intervention. Mean weight losses ranged from 3 kg to 34 kg. Clinical heterogeneity in study characteristics precluded meta-analysis. The effect on serum uric acid (sUA) ranged from -168 to 30 µmol/L, and 0%-60% patients achieving sUA target (<360 µmol/L). Six out of eight studies (75%) showed beneficial effects on gout attacks. Two studies indicated dose-response relationship for sUA, achieving sUA target and gout attacks. At short term, temporary increased sUA and gout attacks tended to occur after bariatric surgery. CONCLUSIONS: The available evidence is in favour of weight loss for overweight/obese gout patients, with low, moderate and low quality of evidence for effects on sUA, achieving sUA target and gout attacks, respectively. At short term, unfavourable effects may occur. Since the current evidence consists of a few studies (mostly observational) of low methodological quality, there is an urgent need to initiate rigorous prospective studies (preferably randomised controlled trials). SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016037937.

Work disability in non-radiographic axial spondyloarthritis patients before and after start of anti-TNF therapy: a population-based regional cohort study from southern Sweden.

Objective: The aim was to assess work-loss days before and after commencement of anti-TNF treatment in patients with non-radiographic axial spondylarthritis (nr-axSpA). Methods: Bionaïve nr-axSpA patients (n = 75), aged 17-62 years, fulfilling the Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis and starting anti-TNF treatment during 2004-11, were retrieved from the observational South Swedish Arthritis Treatment Group study. Patient information was linked to Swedish Social Insurance Agency data on sick leave and disability pension from 1 year before to 2 years after anti-TNF initiation. Matched population references were included for comparison and to adjust for secular trends. Results: The nr-axSpA patients had a median age of 35 years and disease duration of 6 years at the start of treatment. During the 2 years after anti-TNF initiation, mean work-loss days (including both sick leave and disability pension) in the nr-axSpA group decreased significantly from 3.4 to 1.9 times more than among the population references. The effect was seen on sick leave, whereas disability pension levels remained similar in both groups throughout. Conclusion: Anti-TNF therapy in nr-axSpA was associated with a significant and sustained improvement of work disability over 2 years. However, the proportion of work-loss days remained almost twice as high as in the general population at the end of follow-up.

Sick leave in patients with ankylosing spondylitis before and after anti-TNF therapy: a population-based cohort study.

OBJECTIVE: To study levels of sick leave and disability pension before and after TNF-antagonist therapy in AS patients. METHODS: Using the population-based South Swedish Arthritis Treatment Group register, we identified 139 AS patients (aged 18-58 years, 78% men), who between January 2002 and December 2008 started their first treatment with adalimumab, etanercept or infliximab. We linked data to the payment register by the Swedish Social Insurance Agency and calculated the proportion on sick leave in 30-day intervals from 12 months before treatment start until 12 months after. For each AS patient, we randomly selected four subjects from the general population matched for age, sex and area of residence. RESULTS: One to 3 months before treatment, an average of 24% of AS patients were on sick leave. During the first 6 months after treatment start, this fraction dropped to 15%, and further declined to 12% at 12 months (P < 0.001). Comparing AS patients with the general population, the relative risk of being on sick leave 3 months before treatment, treatment start and 12 months after treatment start was 8.0 (95% CI 4.6, 13.9), 9.2 (95% CI 5.4, 15.7) and 4.0 (95% CI 2.1, 6.3), respectively. The decrease in sick leave was not substantially offset by changes in disability pension. CONCLUSION: There is a decline in sick leave during the first 12 months after initiation of TNF-antagonist treatment in AS patients not explained by societal factors or secular trends. The proportion of AS patients on disability pension remained unchanged during the observation period.