mardi 9 août 2016

Xeljanz Offers Better Outcomes in Early RA (CME/CE)

Action Points

  • Note that this post hoc analysis of a clinical trial evaluating tofacitinib, an oral Janus kinase inhibitor, revealed it had higher efficacy among those with a more recent diagnosis of rheumatoid arthritis.
  • Be aware that time-from-diagnosis was based on self-report, as opposed to objective measurements.

The use of tofacitinib (Xeljanz) monotherapy was more effective in reducing the signs and symptoms of early rheumatoid arthritis (RA) versus those of established RA, researchers reported.

Of the 956 patients in the study, 54% had early RA -- defined as less than 1 year duration -- while the rest had established RA. Patients were randomized into three treatment arms of 5 mg tofacitinib two times a day (373), 10 mg two times a day (397), or methotrexate weekly (186). For signs and symptoms of disease, treatment response was statistically significantly greater at 24 months in those patients with early RA who received tofacitinib 5 mg two times a day, according to Roy Fleischmann, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues.

Also, when compared to methotrexate (MTX), monotherapy with the oral Janus kinase inhibitor significantly improved the signs of symptoms of RA, and effectively inhibited joint damage in methotrexate-naïve patients, regardless of the duration of RA, they wrote in RMD Open.

Treatment of RA is designed to achieve disease remission or, if that's not possible, to improve the signs or symptoms of the disease and inhibit or reverse functional disability. Fleischmann's group pointed out that recent studies have demonstrated that disease duration could determine the effectiveness of treatment, suggesting that early treatment offers a way of preserving physical function and preventing disability.

"It has been postulated that the early stages of RA may, therefore, offer a therapeutic window of opportunity in which to prevent joint damage from occurring," they wrote, noting that window could extend anywhere from 3 months to 2 years following the appearance of symptoms.

They carried out a post hoc analysis of the ORAL Start study, a 24-month, phase III trial that compared tofacitinib monotherapy with methotrexate monotherapy in methotrexate-naïve patients with RA.

They evaluated the efficacy of treatment with tofacitinib by using ACR response rates (ACR 20, ACR50, and ACR70) and disease activity scores in 28 joints (DAS28-4) erythrocyte sedimentation rate (DA28-4 ESR). They also assessed physical function using the Health Assessment Questionnaire-Disability Index and used van der Heijde modified total Sharp scores to to evaluate the radiographic progression of joint structural damage.

The authors reported no significant difference between early and established RA in the tofacitinib 10 mg two times a day or methotrexate groups, suggesting that their analysis "did not provide any definitive support for the concept of a window of opportunity."

They also determined that patients with either early or established RA showed a significant reduction in signs and symptoms of disease, as well as improvements in physical functioning and inhibition of radiographic progress when treated with either tofacitinib 5 or 10 mg compared with methotrexate monotherapy.

Additionally, there were no "meaningful differences in safety parameters seen between patients with early and established RA," the authors noted. For instance, 82.1% of those with early RA and in the 5-mg twice daily group experienced treatment-emergent adverse events versus 76.7% with established disease who received 5 mg twice daily.

Fleischmann's group concluded that "in line with the principle of treating to target, the best results with tofacitinib or MTX are obtained in patients with early RA. Therefore, the diagnosis of RA should be made, and treatment started, as early as possible after the development of symptoms."

However, if 3 months of aggressive methotrexate therapy results in a less than significant response, the researchers suggested it would "be reasonable" to add tofacitinib to methotrexate. If methotrexate therapy results in an inadequate response, or if methotrexate is not tolerated, patients could be switched to tofacitinib monotherapy.

The study had limitations including the fact that disease duration was defined by the reporting of the amount of time since diagnosis, rather than by any objective criteria.

"Diagnosis of RA will vary from clinic to clinic, depending on local practice; the fact that the mean duration of disease for patients in the established RA group was around 6 years, but that these patients were still MTX-naive, highlights the potential uncertainty around disease duration for some patients," they stated.

The study was supported by Pfizer. Some co-authors are company employees.

Fleischmann disclosed relevant relationships with Pfizer. Co-authors disclosed relevant relationships with Dutch Arthritis Foundation, the Dutch NIH, the EU, Merck, UCB, Bristol-Myers Squibb, Biotest AG, Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boehringer, Takeda, Eli Lilly, AbbVie, BiogenIDEC, Biotest, Celgene, GlaxoSmithKline, Jansen, MSD, and Vertex.

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Xeljanz Offers Better Outcomes in Early RA (CME/CE)

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