Giant cell arteritis associated with PD-1 inhibition.

A 50-year-old woman was referred to rheumatology for new onset polyarthralgia and headache. She had a history of metastatic lung adenocarcinoma and was started on treatment with the programmed death 1 receptor (PD-1) antagonist pembrolizumab 2 months prior. Examination revealed left temporal artery tenderness and hand synovitis. Investigations revealed enlarged temporal artery on ultrasound imaging. On steroid treatment, she had resolution of symptoms, but due to significant steroid side effects required methotrexate and her PD-1 antagonist therapy was continued in consultation with her oncologist. Her malignant disease has remained stable, and she has improved functional status.

Pharmacogenetics in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic inflammatory arthritis leading to severe joint damage and associated with high morbidity and mortality. Disease-modifying antirheumatic drugs (DMARDs) are the mainstay of treatment in RA. DMARDs not only relieve the clinical signs and symptoms of RA but also inhibit the radiographic progression of disease. In the last decade, a new class of disease-modifying medications, the biologic agents, has been added to the existing spectrum of DMARDs in RA. However, patients' response to these agents is not uniform with considerable variability in both efficacy and toxicity. There are no reliable means of predicting an individual patient's response to a given DMARD prior to initiation of therapy. In this chapter, the current published literature on the pharmacogenetics of traditional DMARDS and the newer biologic DMARDs in RA is highlighted. Pharmacogenetics may help individualize drug therapy in patients with RA in the near future.

Clinical trials in systemic lupus erythematosus: a status report on ongoing trials.

To describe the characteristics of trials in systemic lupus erythematous (SLE) listed in ClinicalTrials.gov such as study design, funding sources and aspects of the disease and drugs under investigation. We conducted a survey of ongoing clinical trials that were registered in the ClinicalTrials.gov website. We used the advanced search option and applied the following inclusion criteria, "SLE," "open studies," "interventional," and "adults 18 years or older." Of 97 eligible studies, 34.0 % were phase 3 or 4, 49.5 % were phase 1, 2 or 2/3 and in 16.5 %, we could not determine the study phase. Most trials were randomized (69.0 %) and 48.4 % were double blinded; 34 % of the trials were placebo controlled, 19.6 % had an active agent comparator and 46.4 % had no comparator. Universities and pharmaceutical industries were the primary sponsors for 45.3 and 39.1 % of the trials, respectively, and government agencies for 10.3 %. Multi-center trials based in the USA (US) accounted for 40.2 % of the trials, 46.4 % were outside of the US and 13.4 % were in the US as well as other countries. The most frequently used endpoint was drug efficacy (30.9 %) followed by disease severity indices (25.7 %), drug safety (14.4 %), remission rates and times to remission (7.2 %), and inflammatory markers and antibody titers (7.2 %). The majority of ongoing clinical trials in SLE are university or industry-funded, randomized phase 1, 2, or 2/3 trials, focused on drug efficacy. Federal funding for trials in SLE within and outside the US remains low.

Clinical trials in rheumatoid arthritis: a status report from the ClinicalTrials.gov website.

The aims of this study are to describe the characteristics of clinical trials in rheumatoid arthritis (RA) listed in ClinicalTrials.gov and examine existing trends in study design, funding sources, outcomes, and drugs under investigation. We conducted a survey of ongoing clinical trials in RA registered in the ClinicalTrials.gov website. We used the advanced search option and applied the following inclusion criteria, "rheumatoid arthritis", "open studies", "interventional", and "adults 18 years or older". Of 127 eligible trials, 53.5% of the studies were either phase 3 or 4, and 40.2% were phase 1, 2, and 2/3. Two-thirds of the trials were randomized (70.9%), and over half were, in addition, double-blinded (53.5%) and placebo-controlled (53.5%). Universities were listed as the primary sponsor for 18.9% of the trials and pharmaceutical industry for 73.2%. Majority of the trials were multi-center studies (93%) conducted outside the United States (54.3%). The most frequently used endpoint was drug efficacy (54.3%) followed by drug safety (25.2%). Most industry-funded trials were open for less than 12 months, whereas most university-funded trials were open for more than 24 months (58% each). Biologic therapies were the focus of most trials in the registry (78.5%). Randomized, double-blinded, placebo-controlled, phase 3 and 4 trials form the majority of ongoing clinical trials in RA. The preponderance of industry funding of RA trials and the short duration of such trials are troubling trends which need to be addressed.