Upadacitinib in patients with psoriatic arthritis and inadequate response to biologics: 3-year results from the open-label extension of the randomised controlled phase 3 SELECT-PsA 2 study.

OBJECTIVES: To assess the long-term safety and efficacy of upadacitinib in patients with psoriatic arthritis (PsA) and an inadequate response (IR) to biologic disease-modifying anti-rheumatic drugs (bDMARDs) who completed up to 152 weeks of treatment in the SELECT-PsA 2 study (ClinicalTrials.gov: NCT03104374). METHODS: Patients were randomised to receive blinded upadacitinib 15 or 30 mg once daily (QD), or placebo for 24 weeks followed by upadacitinib 15 or 30 mg QD. After 56 weeks, patients were eligible to enter an open-label extension (OLE) in which they continued their assigned dose of upadacitinib. Efficacy and safety were assessed through 152 weeks. A subanalysis of patients with IR to tumour necrosis factor inhibitors (TNFis) was also conducted. RESULTS: In total, 450 patients entered the OLE and 358 completed 152 weeks of treatment. Improvements in efficacy outcomes observed at week 56, including the proportion of patients achieving: 20/50/70% improvement in American College of Rheumatology criteria, minimal disease activity, and 75/90/100% improvement in Psoriasis Area and Severity Index, were maintained through week 152. Efficacy outcomes in the TNFi-IR subgroup were similar to those reported in the overall population. Upadacitinib was well tolerated throughout long-term treatment, with no cumulative adverse effects observed through 152 weeks. CONCLUSIONS: Efficacy of upadacitinib was maintained up to 152 weeks of treatment in this highly treatment-refractory population of patients with PsA. The long-term safety profile of upadacitinib 15 mg was consistent with its known safety profile across indications; no new safety signals were identified.

Association Between Achievement of Clinical Disease Control and Improvement in Patient-Reported Outcomes and Quality of Life in Patients With Psoriatic Arthritis in the Phase 3 SELECT-PsA 1 and 2 Randomized Controlled Trials.

OBJECTIVE: We explored the relationship between achievement of clinical disease control and improvements in and normative values for patient-reported outcomes (PROs), including quality of life (QoL) measures, in patients with psoriatic arthritis (PsA). METHODS: This was a post hoc analysis of 104-week data from the SELECT-PsA 1 and 2 trials in adults with PsA and inadequate response to one or more conventional synthetic (SELECT-PsA 1) or biologic (SELECT-PsA 2) disease-modifying antirheumatic drug. Patients were initially randomized to upadacitinib 15 mg once daily (QD) to placebo switched to upadacitinib 15 mg QD at week 24 or to adalimumab 40 mg every other week (SELECT-PsA 1 only), and data were pooled across treatments and analyzed. We evaluated several clinical disease control measures (minimal disease activity [MDA]; very low disease activity [VLDA]; and low disease activity [LDA] and/or remission by Disease Activity in Psoriatic Arthritis [DAPSA], Psoriatic Arthritis Disease Activity Score [PASDAS], and Routine Assessment of Patient Index Data 3 [RAPID3]) and examined their associations with improvements and normative values for various PROs. RESULTS: A total of 1,069 and 317 patients were analyzed for SELECT-PsA 1 and 2, respectively. In both studies, responders (patients who achieved MDA or VLDA, and DAPSA, PASDAS, and RAPID3 LDA or remission) at week 104 achieved more marked changes from baseline, and more responders achieved normative values in PROs compared with nonresponders (most nominal P < 0.0001). Furthermore, numerically larger proportions of responders achieved minimal clinically important differences across PROs compared with nonresponders in both studies. In addition, patients who achieved MDA or VLDA were more likely to achieve DAPSA, PASDAS, and RAPID3 LDA or remission (all nominal P < 0.0001) for upadacitinib 15 mg QD and when treatment arms were pooled. CONCLUSION: Patients with PsA who achieve clinical disease control are more likely to achieve improvements and normative values in PROs and QoL measures, which reinforces disease control as a treatment target.

Obesity, waist circumference, weight change, and the risk of psoriasis in women: Nurses' Health Study II.

BACKGROUND: Psoriasis is a common, chronic, inflammatory skin disorder. Higher adiposity may increase the risk of psoriasis, but, to our knowledge, no prospective data are available on this relationship. METHODS: We prospectively examined the relationships between body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), weight change, waist circumference, hip circumference, waist-hip ratio, and incident psoriasis in 78 626 women over a 14-year period (1991-2005) in the Nurses' Health Study II. The primary outcome was incident, self-reported, physician-diagnosed psoriasis. RESULTS: During the 14 years of follow-up, there were 892 self-reported incident cases of psoriasis. There was a graded positive association between BMI measured at multiple time points and the risk of incident psoriasis. When we analyzed BMI updated every 2 years, compared with a BMI of 21.0 through 22.9, the multivariate relative risks of psoriasis were 1.40 (95% confidence interval [CI], 1.13-1.73) for a BMI of 25.0 through 29.9; 1.48 (95% CI, 1.15-1.91) for a BMI of 30.0 through 34.9; and 2.69 (95% CI, 2.12-3.40) for a BMI of 35.0 or greater (P for trend, < .001). For BMI at the age of 18 years, the multivariate relative risk for the top BMI category (> or = 30.0) was 1.73 (95% CI, 1.24-2.41) and that for a lower BMI category (< 21.0) was 0.76 (95% CI, 0.65-0.90) (P for trend, < .001). Weight gain from the age of 18 years, higher waist circumference, hip circumference, and waist-hip ratio were all associated with a higher risk of incident psoriasis (all P values for trend, < .001). CONCLUSION: This large prospective study indicates that increased adiposity and weight gain are strong risk factors for incident psoriasis in women.

Gout affecting the hand and wrist.

Tophaceous gout in the hand and wrist often presents de novo as the first sign of the disease process in the elderly. Tophaceous material may present in a liquid, pasty, or chalky/granular state. Treatment may be as simple as aspirating the liquid or squeezing out pasty tophaceous material. Other nonsurgical treatment options include lifestyle and dietary modifications and drug therapy. Surgery is often indicated for the patient with significant tendon and joint compromise as well as skin breakdown and for decompression of compressive peripheral neuropathy.

Complicated hypertension related to the abuse of ephedrine and caffeine alkaloids.

Ephedra containing products (ECPs), which most often contain additional sources of caffeine alkaloids, may be an under-recognized cause of hypertension. ECPs, especially when used in combination or at higher than recommended doses, can cause life-threatening cardiovascular and neurological complications. We present a case of hypertensive encephalopathy with new onset generalized tonic-clonic seizure secondary to concomitant use of two OTC supplements containing a mixture of ephedrine and caffeine alkaloids.

Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects.

OBJECTIVE: To review the literature on herbal preparations commonly utilized in the treatment of rheumatic indications. METHODS: Search of MEDLINE (PubMed) was performed using both the scientific and the common names of herbs. Relevant articles in English were collected from PubMed and reviewed. RESULTS: This review summarizes the efficacy and toxicities of herbal remedies used in complementary and alternative medical (CAM) therapies for rheumatologic conditions, by elucidating the immune pathways through which these preparations have antiinflammatory and/or immunomodulatory activity and providing a scientific basis for their efficacy. Gammalinolenic acid suppresses inflammation by acting as a competitive inhibitor of prostaglandin E2 and leukotrienes (LTs) and by reducing the auto-induction of interleukin1alpha (IL-1alpha)-induced pro-IL-1beta gene expression. It appears to be efficacious in rheumatoid arthritis (RA) but not for Sjogrens disease. The antiinflammatory actions of Harpagophytum procumbens is due to its action on eicosanoid biosynthesis and it may have a role in treating low back pain. While in vitro experiments with Tanacetum parthenium found inhibition of the expression of intercellular adhesion molecule-1, tumor necrosis factor alpha (TNF-alpha), interferon-gamma, IkappaB kinase, and a decrease in T-cell adhesion, to date human studies have not proven it useful in the treatment of RA. Current experience with Tripterygium wilfordii Hook F, Uncaria tomentosa, finds them to be efficacious in the treatment of RA, while Urtica diocia and willow bark extract are effective for osteoarthritis. T. wilfordii Hook F extract inhibits the production of cytokines and other mediators from mononuclear phagocytes by blocking the up-regulation of a number of proinflammatory genes, including TNF-alpha, cyclooxygenase 2 (COX-2), interferon-gamma, IL-2, prostaglandin, and iNOS. Uncaria tomentosa and Urtica diocia both decrease the production of TNF-alpha. At present there are no human studies on Ocimum spp. in rheumatic diseases. The fixed oil appears to have antihistaminic, antiserotonin, and antiprostaglandin activity. Zingiber officinale inhibits TNF-alpha, prostaglandin, and leukotriene synthesis and at present has limited efficacy in the treatment of osteoarthritis. CONCLUSIONS: Investigation of the mechanism and potential uses of CAM therapies is still in its infancy and many studies done to date are scientifically flawed. Further systematic and scientific inquiry into this topic is necessary to validate or refute the clinical claims made for CAM therapies. An understanding of the mechanism of action of CAM therapies allows physicians to counsel effectively on their proper and improper use, prevent adverse drug-drug interactions, and anticipate or appreciate toxicities. RELEVANCE: The use of CAM therapies is widespread among patients, including those with rheumatic diseases. Herbal medications are often utilized with little to no physician guidance or knowledge. An appreciation of this information will help physicians to counsel patients concerning the utility and toxicities of CAM therapies. An understanding and elucidation of the mechanisms by which CAM therapies may be efficacious can be instrumental in discovering new molecular targets in the treatment of diseases.

Giant cell arteritis - a series of cases and review of literature.

Giant cell arteritis is the most frequently occurring primary vasculitis in European and North American adults over the age of 50 years. It usually presents with constitutional symptoms like fatigue, malaise and fevers with a temporal headache. We present a series of three interesting cases of the disease, discuss the differential diagnosis and review the literature on the same.

Psoriasis and the risk of diabetes and hypertension: a prospective study of US female nurses.

OBJECTIVE: To evaluate the independent association between psoriasis and risk of diabetes and hypertension. DESIGN: A prospective study of female nurses who were followed up from 1991 to 2005. SETTING: Nurses' Health Study II, a cohort of 116 671 US women aged 27 to 44 years in 1991. PARTICIPANTS: The study included 78 061 women who responded to a question about a lifetime history of physician-diagnosed psoriasis in 2005. Women who reported a diagnosis of diabetes or hypertension at baseline were excluded. Main Outcome Measure New diagnosis of diabetes or hypertension, obtained from biennial questionnaires. RESULTS: Of the 78 061 women, 1813 (2.3%) reported a diagnosis of psoriasis. During the 14 years of follow-up, a total of 1560 incident cases (2%) of diabetes and 15 724 incident cases (20%) of hypertension were documented. The multivariate-adjusted relative risk of diabetes in women with psoriasis compared with women without psoriasis was 1.63 (95% confidence interval, 1.25-2.12). Women with psoriasis were also at an increased risk for the development of hypertension (multivariate relative risk, 1.17; 95% confidence interval, 1.06-1.30). Age, body mass index, and smoking status did not significantly modify the association between psoriasis and risk of diabetes or hypertension (P values for interaction, > or =.07). CONCLUSIONS: In this prospective analysis, psoriasis was independently associated with an increased risk of diabetes and hypertension. Future studies are needed to find out whether psoriasis treatment will reduce the risk of diabetes and hypertension.

Psoriatic arthritis epidemiology.

Recent studies have added to our knowledge of the epidemiology of psoriatic arthritis (PsA) across various populations. Absence of a standard case definition and the relative rarity of PsA may have contributed to the paucity of available data to date. Reported prevalence estimates appear to vary more than incidence estimates. Prevalence estimates may vary as a result of differences in genetic factors, exposure to environmental factors, and study methods. Although prevalence data among different subgroups and extrapolation from clinical and laboratory data allow some inferences about the role of various potential risk factors for PsA, only one study has investigated them specifically. Overall, quality of life in PsA appears similar to that in rheumatoid arthritis, whereas available data on the mortality impact of PsA are conflicting, preventing a unified conclusion. This review summarizes recent data on PsA epidemiology.

Smoking and the risk of psoriasis in women: Nurses' Health Study II.

BACKGROUND: Psoriasis is a common, chronic, inflammatory skin disorder. Smoking may increase the risk of psoriasis, but no prospective data are available on this relation. METHODS: We prospectively examined over a 14-year time period (1991-2005) the relation between smoking status, duration, intensity, cessation, and exposure to secondhand smoke, and incident psoriasis in 78,532 women from the Nurses Health Study II. The primary outcome was incident, self-reported, physician-diagnosed psoriasis. RESULTS: We documented 887 incident cases of psoriasis. Compared with those who had never smoked, the multivariate relative risk (RR) of psoriasis was 1.78 (95% confidence interval [CI], 1.46 to 2.16) for current smokers and 1.37 (95% CI, 1.17 to 1.59) for past smokers. Compared with nonsmokers, the multivariate RR of psoriasis was 1.60 (95% CI, 1.31 to 1.97) for those who had smoked 11-20 pack-years and 2.05 (95% CI, 1.66 to 2.53) for those who had smoked > or =21 pack-years. Compared with never smokers, the multivariate RR of psoriasis was 1.61 (95% CI, 1.30 to 2.00) for those who quit smoking <10 years ago, 1.31 (95% CI, 1.05 to 1.64) for 10-19 years ago, and 1.15 (95% CI, 0.88 to 1.51) for > or =20 years ago. Prenatal and childhood exposure to passive smoke was associated with an increased risk of psoriasis. CONCLUSIONS: In this prospective analysis, current and past smoking, and cumulative measures of smoking were associated with the incidence of psoriasis. The risk of incident psoriasis among former smokers decreases nearly to that of never smokers 20 years after cessation.