PracticeUpdate: Dermatology & Rheumatology

ACR 2016 25

More and more patients with RA achieving radiographic remission The proportion of patients who meet radiographic remission at 10 years after diagnosis of early rheumatoid arthritis has increasing over recent years, report results of a prospective, single-centre study.

T uulikki Sokka, MD, PhD, of Jyvaskyla Central Hospital, Jyväskylä, Finland, explained that radio- graphs of the hands and feet represent an objective outcome measure in rheumatoid arthritis. Joint damage results from cumulative disease activity over years. Unlike other clinical measures, radiographic damage is caused mainly by disease inflammatory activity. Radio- graphs, therefore, provide a proper measure to analyse outcomes of rheumatoid arthritis over the long term. Dr Sokka and colleagues set out to analyse radiographic remission in patients with early rheumatoid arthritis 10 years after their diagnosis in a real-life setting. All 1046 patients who were diagnosed with rheumatoid arthritis from 1997 to 2005 were scheduled for 10-year follow-up incorporating radiographs of their hands and feet. They had undergone such radiography at years 0, 2, 5, as well. Larsen score (0–100) was employed including metacarpophalangeal joints, wrists, and two to five meta- tarsophalangeal joints.

seropositive, 13% with erosions at baseline), 743 patients (70% women, mean age 54 years, 65% seropositive, 12% with erosions at baseline) attended their 10-year follow-up visit. Among 480 seropositive patients, median progression of Larsen score was 3 (interquartile range 0, 8) and in 263 seronegative patients, this score was 0 (interquartile range 0, 2). Radiographic remission had been achieved at the 10-year follow-up visit in 31%, 40%, and 56% of seropositive patients who were diagnosed in 1997–1999, 2000–2002, and 2003– 2005, respectively; P < 0.001. In seronegative patients, these figures were 75%, 79%, and 83%, respectively. Over 10 years, antirheumatic medications included meth- otrexate in 79%, 84%, and 90% of patients diagnosed in 1997–1999, 2000–2002, and 2003–2005; subcutaneous methotrexate in 13%, 24%, and 25%; sulfasalazine in 82%, 83%, and 72%; hydroxychloroquine in 61%, 73%, and 76%; leflunamide in 13%, 16%, and 14%; intramuscular gold in 19%, 11% and 5%; prednisone in 63%, 80%, and 82%; and biologic agents in 10%, 16%, and 19%of patients, respectively. Death (15% of women and 30% of men died over 10 years) was the main reason for missing data. Dr Sokka concluded that the proportion of patients who meet radiographic remission at 10 years after diagnosis of early rheumatoid arthritis has been increasing over recent years. A majority of patients with seropositive rheumatoid arthritis who were seen at 10-year follow-up in 2013–2015 met criteria for radiographic remission. Over the observation period, the use of methotrexate, sub- cutaneous methotrexate, hydroxychloroquine, prednisone, and biologics increased; and sulfasalazine and intramus- cular gold use declined.

Radiographic remission was de- fined as no new erosions and no worsening of erosions between baseline (at diagnosis) and 10 years. The proportion of patients with radiographic remission or no remission 10 years after diagnosis was compared in patients with a new diagnosis of rheumatoid arthritis in 1997–1999, 2000– 2002, and 2003–2005. Among 1046 patients (66% women, mean age 58 years, 60%

Over the observationperiod, the use ofmethotrexate, subcutaneousmethotrexate, hydroxychloroquine, prednisone, and biologics increased; and sulfasalazine

and intramuscular gold use declined.

that predicted therapy responses. Eight genes predicted general responsiveness to both tumour necrosis factor inhibition and rituximab, 23 genes predicted responsiveness to tumour necrosis factor inhibition, and 23 genes predicted responsiveness to rituximab. The researchers tested their prediction models on the validation set, which resulted in receiver operating characteristic plot points with an area under the curve of 91.6% for general responsiveness, 89.7% for tumour necrosis factor inhibition response, and 85.7% for rituximab response. Dr Porter said, “There are indeed gene expression markers that predict drug-specific response. If confirmed, this will allow stratification of patients into groups more

likely to respond to one drug rather than another. This would lead to higher response rates and a reduced likelihood of receiving an ineffective drug. Since ineffective treatment is associated with pain, stiffness, disability, and reduced quality of life, this identification will lead to better patient care.” He added that the next step will be to confirm these models. “The findings need to be confirmed using targeted RNA sequencing, or internal validation, and then tested in a new cohort of patients (external validation). Ultimately, a commercial testing kit would be developed to allow clinicians to test patients before they receive treatment to guide them to the most effective treatment,” he said.

and globin RNA. They used 70% of the sam- ples to develop response prediction models, and reserved 30% for validation. Clinical response to the therapies was de- fined as a drop in Disease Activity Score 28–Erythrocyte Sedimentation Rate of 1.2 units between baseline and 3 months. They used multiple machine learning tools to pre- dict general responsiveness and differential responses to tumour necrosis factor inhibition and rituximab. They also used tenfold cross-validation to train the models for responsiveness. They then tested these on the validation samples. Using support vector machine recursive feature elimination, the researchers identified three gene expression signatures

DECEMBER 2016