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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 (ClinicalTrials.gov): 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. [ABSTRACT FROM AUTHOR]

The original article titled "Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis" has issued a correction notice. The correction pertains to Table 5 of the article, which contained incorrect values for serious adverse events (SAEs) within the rheumatoid arthritis (RA) section for different patient subgroups. The correct values for the age ≥ 65 years, female sex, and male sex patient subgroups are 21.27%, 16.50%, and 19.06%, respectively. The corrected table is provided in the correction notice. [Extracted from the article]

Objectives: Tofacitinib is a Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ulcerative colitis, and has been investigated in psoriasis (PsO). Routine pharmacovigilance of an ongoing, open-label, blinded-endpoint, tofacitinib RA trial (Study A3921133; NCT02092467) in patients aged ≥50 years and with ≥1 cardiovascular risk factor identified a higher frequency of pulmonary embolism (PE) and all-cause mortality for patients receiving tofacitinib 10 mg twice daily versus those receiving tumour necrosis factor inhibitors and resulted in identification of a safety signal for tofacitinib. Here, we report the incidence of deep vein thrombosis (DVT), PE, venous thromboembolism (VTE; DVT or PE) and arterial thromboembolism (ATE) from the tofacitinib RA (excluding Study A3921133), PsA and PsO development programmes and observational studies. Data from an ad hoc safety analysis of Study A3921133 are reported separately within.Methods: This post-hoc analysis used data from separate tofacitinib RA, PsO and PsA programmes. Incidence rates (IRs; patients with events per 100 patient-years' exposure) were calculated for DVT, PE, VTE and ATE, including for populations stratified by defined baseline cardiovascular or VTE risk factors. Observational data from the US Corrona registries (including cardiovascular risk factor stratification), IBM MarketScan research database and the US FDA Adverse Event Reporting System (FAERS) database were analysed.Results: 12 410 tofacitinib-treated patients from the development programmes (RA: n=7964; PsO: n=3663; PsA: n=783) were included. IRs (95% CI) of thromboembolic events among the all tofacitinib cohorts' average tofacitinib 5 mg and 10 mg twice daily treated patients for RA, respectively, were: DVT (0.17 (0.09-0.27) and 0.15 (0.09-0.22)); PE (0.12 (0.06-0.22) and 0.13 (0.08-0.21)); ATE (0.32 (0.22-0.46) and 0.38 (0.28-0.49)). Among PsO patients, IRs were: DVT (0.06 (0.00-0.36) and 0.06 (0.02-0.15)); PE (0.13 (0.02-0.47) and 0.09 (0.04-0.19)); ATE (0.52 (0.22-1.02) and 0.22 (0.13-0.35)). Among PsA patients, IRs were: DVT (0.00 (0.00-0.28) and 0.13 (0.00-0.70)); PE (0.08 (0.00-0.43) and 0.00 (0.00-0.46)); ATE (0.31 (0.08-0.79) and 0.38 (0.08-1.11)). IRs were similar between tofacitinib doses and generally higher in patients with baseline cardiovascular or VTE risk factors. IRs from the overall Corrona populations and in Corrona RA patients (including tofacitinib-naïve/biologic disease-modifying antirheumatic drug-treated and tofacitinib-treated) with baseline cardiovascular risk factors were similar to IRs observed among the corresponding patients in the tofacitinib development programme. No signals of disproportionate reporting of DVT, PE or ATE with tofacitinib were identified in the FAERS database.Conclusions: DVT, PE and ATE IRs in the tofacitinib RA, PsO and PsA programmes were similar across tofacitinib doses, and generally consistent with observational data and published IRs of other treatments. As expected, IRs of thromboembolic events were elevated in patients with versus without baseline cardiovascular or VTE risk factors, and were broadly consistent with those observed in the Study A3921133 ad hoc safety analysis data, although the IR (95% CI) for PE was greater in patients treated with tofacitinib 10 mg twice daily in Study A3921133 (0.54 (0.32-0.87)), versus patients with baseline cardiovascular risk factors treated with tofacitinib 10 mg twice daily in the RA programme (0.24 (0.13-0.41)). [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of baseline risk factors on radiographic progression in patients with active psoriatic arthritis (PsA) who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and were treated with tofacitinib or adalimumab (ADA).Methods: Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. OPAL Broaden was a 12-month, double-blind phase III trial. Patients received tofacitinib 5 mg twice daily (BID; n = 107), tofacitinib 10 mg BID (n = 104), or ADA 40 mg once every 2 weeks (n = 106), all with 1 background csDMARD. Radiographs (baseline and Month 12) were scored using the van der Heijde-modified total Sharp score (mTSS) for PsA. Radiographic nonprogression was defined as an increase from baseline in mTSS ≤ 0.5, ≤ 0, or ≤ 0.66. Changes from baseline in mTSS and nonprogression (≤ 0.5 increase from baseline in mTSS) were analyzed by baseline C-reactive protein (CRP) > 2.87 or ≤ 2.87 mg/l. Baseline predictors of radiographic progression were analyzed.Results: At Month 12, > 90% of patients receiving tofacitinib or ADA met all radiographic nonprogression criteria. Mean changes from baseline through Month 12 in mTSS, erosion, and joint space narrowing scores were close to 0. Changes in radiographic outcomes were minimal, irrespective of baseline CRP levels > 2.87 or ≤ 2.87 mg/l, with a small numerical difference observed for tofacitinib 5 mg BID. A significant relationship was observed between baseline CRP level and increases from baseline in mTSS > 0.5 at Month 12.Conclusion: Elevated CRP levels at baseline were associated with greater structural progression. Changes in radiographic outcomes were minimal regardless of CRP levels. [Clinical trial registration number (www.ClinicalTrials.gov): NCT01877668]. [ABSTRACT FROM AUTHOR]

Objective. The Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials and longitudinal observational studies has recently been updated. The joint counts are central to the measurement of the peripheral arthritis component of the musculoskeletal (MSK) disease activity domain. We report the Outcome Measures in Rheumatology (OMERACT) 2018 meeting's approaches to seek endorsement of the 66/68 swollen and tender joint count (SJC66/TJC68) for inclusion in the PsA Core Outcome Measurement Set (COS). Methods. Using the OMERACT Filter 2.1 Instrument Selection Process, the SJC66/TJC68 was assessed for (1) domain match, (2) feasibility, (3) numerical sense (construct validity), and (4) discrimination (test retest reliability, longitudinal construct validity, sensitivity in clinical trials, and thresholds of meaning). A protocol was designed to assess the measurement properties of the SJC66/TJC68 joint count. The results were summarized in a Summary of Measurement Properties table developed by OMERACT. OMERACT members discussed and voted on whether the strength of the evidence supported that the SJC66/TJC68 had passed the OMERACT Filter as an outcome measurement instrument for the PsA COS. Results. OMERACT delegates endorsed the use of the SJC66/TJC68 for the measurement of the peripheral arthritis component of the MSK disease activity domain. Among patient research partners, 100% voted for a "green" endorsement, whereas among the group of other stakeholders, 88% voted for a "green" endorsement. Conclusion. The SJC66/TJC68 is the first fully endorsed outcome measurement instrument using the OMERACT Filter 2.1 and the first instrument fully endorsed within the PsA COS. [ABSTRACT FROM AUTHOR]

Objective. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) psoriatic arthritis (PsA) working group is developing a Core Outcome Measurement Set for PsA clinical trials [randomized controlled trials (RCT) and longitudinal observational studies (LOS)] using the OMERACT Filter 2.1 instrument selection algorithm. Our objective was to assess the Psoriatic Arthritis Impact of Disease questionnaire (PsAID12) for the measurement of the core domain PsA-specific health-related quality of life (HRQOL). Methods. PsAID12 measurement property evidence gathered in a systematic literature review, and additional analyses conducted in LOS, were used to inform a consensus process. Analyses that had not been published were independently reviewed by the OMERACT technical advisory group. Data and process were presented, discussed in breakout groups, and voted on at the OMERACT conference (Terrigal, Australia, May 2018). Results. PsAID12 fulfilled the green (good to go) OMERACT standards for domain match, feasibility, reliability, and construct/longitudinal construct validity. Discrimination and thresholds of meaning were amber (caution but good enough to go forward). The overall working group recommendation was amber/provisional endorsement of PsAID12 for measuring PsA-specific HRQOL in RCT and LOS. Of 96 participants who voted at the PsA OMERACT workshop, 87.5% (84) voted "yes" to endorse this recommendation; 14 of the 96 were patient research partners (PRP) and 93% of them (13) voted "yes"; 82 participants were not PRP and 87% of them (71) voted "yes." Conclusion. At OMERACT 2018, PsAID12 was the first patient-reported outcome measure provisionally endorsed as a core outcome measure for disease-specific HRQOL in PsA clinical trials. PsAID12 discrimination and improvement thresholds will be studied in future RCT. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a chronic, inflammatory disease. The effects of PsA real-world treatment patterns on patient-reported outcomes in the US and 5 European countries (EU5; France, Germany, Italy, Spain, UK) were evaluated. Respondents from the 2016 National Health and Wellness Survey received advanced therapies (e.g., biologic disease-modifying antirheumatic drugs [DMARDs]), other therapies, (e.g., conventional synthetic DMARDs), or no treatment. Assessments included demographics, disease severity (patient-reported), comorbidities (Charlson Comorbidity Index), health status (Short Form-36 Health Survey), depression (Patient Health Questionnaire-9), work productivity (Work Productivity and Activity Index), and treatment adherence (Morisky Medication Adherence Scale-8). Overall, 1037 respondents from the US and 947 respondents from the EU5 were included. Of these, 21.7% US and 7.3% EU5 respondents received advanced therapies; 16.6% and 28.5%, other therapies; and 61.7% and 64.2%, no treatment, respectively. During treatment with advanced or other therapies, 40.8-54.7% US and 57.7-58.9% EU5 respondents self-reported moderate or severe PsA. Respondents receiving advanced therapies had the highest Charlson Comorbidity Index score (US, 1.25; EU5, 1.42); the lowest scores were with no treatment (0.52 and 0.49, respectively). Employment was lowest with other therapies (US, 47.7%; EU5, 41.1%). Overall work impairment was reported by 57.9% US and 62.6% EU5 respondents receiving advanced therapies. Medication adherence was generally low in the US and medium in the EU5 (Morisky Medication Adherence Scale-8: low, US 40.1-46.7%, EU5, 29.0-35.2%; medium, US 29.3-36.1%, EU5 37.8-49.3%; high, US 23.8-24.0%; EU5, 21.7-27.0%). Advanced and other therapies reduced PsA severity; however, > 40% of respondents reported moderate or severe PsA during treatment. Better management and adherence may reduce unmet need and disease burden. Further work is required to improve PsA diagnosis and time to treatment initiation. [ABSTRACT FROM AUTHOR]

Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). These post hoc exposure–response (E–R) analyses of pooled data from two Phase 3 studies (NCT01877668 and NCT01882439) characterized the relationships between tofacitinib exposure and efficacy (American College of Rheumatology [ACR] criteria), and changes in hemoglobin (Hgb) in patients with PsA. Efficacy data for the proportion of patients receiving tofacitinib 5 or 10 mg twice daily, or placebo, achieving ACR ≥20%, ≥50%, or ≥70% response criteria (ACR20, ACR50, and ACR70, respectively) at Month 3, were modeled jointly using a four‐category ordered categorical exposure–response model (ACR20 non‐responder, ACR20 responder but not ACR50 responder, ACR50 responder but not ACR70 responder, and ACR70 responder). A maximum drug effect (Emax) model (using average concentrations of tofacitinib at steady state [Cavg]) adequately described the exposure–ACR response rate relationship. Model‐predicted response rates for tofacitinib 5 and 10 mg twice daily were 51% and 58%, respectively, for ACR20; 29% and 36% for ACR50; and 15% and 20% for ACR70. The E–R relationship between tofacitinib exposure and changes in Hgb was assessed using an indirect response model, which generally predicted Hgb concentration–time profiles across treatments well. The proportions of patients experiencing a decrease in Hgb of >2 g/dL were similar with tofacitinib 5 mg twice daily or placebo. These results were generally consistent with previous analyses in rheumatoid arthritis and psoriasis, and support the use of tofacitinib 5 mg twice daily for active PsA. [ABSTRACT FROM AUTHOR]