US study shows that tofacitinib is an efficacious treatment for active RA

Results of a Phase III study presented today at the EULAR 2011 Annual Congress show that at 6 months, 58.3 percent of patients who had previously not responded to treatment with DMARDs, achieved ACR20 response (a 20 percent improvement in symptoms) when treated with the novel oral Janus kinase inhibitor tofacitinib at 10mg BID compared to 31.2 percent in the placebo group. Significant improvements were also observed in the 5 mg BID dose.

Most adverse events were mild and no new safety signals were reported, according to study authors.

Results of the 12 month multinational study, conducted with 792 patients also show that 36.6% and 16.2% of patients achieved ACR50 and ACR70 responses respectively in the 10mg BID group, a significant improvement in symptoms compared to placebo, where 31.2%, 12.7% and 3.2% of patients achieved ACR 20, 50 and 70 respectively. Significant improvements in the Disease Activity Score physician index (DAS28***) were also observed in the treatment groups compared to placebo, along with improvements in the Health Assessment Questionnaire**** (HAQ) compared to placebo.

"We know that JAK plays a fundamental role in the signalling pathways that regulate RA and interrupting the uncontrolled inflammatory cascades seen in this study provides a novel way of modifying the progression of the disease said Professor Joel Kremer of the Albany Medical College in Albany USA. "Tofacitinib appears to reduce the signs and symptoms of RA very rapidly, and we hope that after carefully considering the benefit/risk equation that this compound will provide an additional valuable treatment option for patients who have experienced an inadequate response to prior treatments."

According to researchers, significant ACR 20, ACR50 and ACR70 responses were seen after 2 weeks of therapy (results not published). Patients received concurrent non-biologic background therapy with DMARDs (including methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, penicillamine and gold, both as single agents and as combination therapies). 81.4% of the 792 patients studied were female, with ages ranging between 50.8-53.3 years. Whilst the majority of adverse events reported were mild (infections and infestations), four deaths were reported in the 5 mg and 10mg BID arms. Four opportunistic infections were also reported.

Results of a further, multinational Phase III tofacitinib study (SAT0243) of 610 patients analysing selected subgroups in the USA have shown that clinically significant efficacy and safety was demonstrated in a number of subgroups investigated, including age, weight, prior DMARD status and the presence of RF / anti-CCP antibodies. Of note, patients who were younger (those aged up to 65 years), slimmer (those weighing less than 50kg), those testing positive to anti-CCP and negative to Rheumatoid Factor showed an improved response to 5mg or 10mg tofacitinib compared to placebo.

Abstract Number: LB0005; SAT0243

*DMARD is the acronym given to a disease modifying anti-rheumatic disease medication

**ACR (American College of Rheumatology) criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters: acute phase reactant (such as sedimentation rate), patient assessment, physician assessment, pain scale and disability/functional questionnaire. ACR20 refers to a 20% improvement in tender/swollen joint counts, as well as three of the five other criteria. ACR50 refers to a 50% improvement and ACR70 refers to a 70% improvement.

***DAS28 (Disease Activity Score) is an index used by physicians to measure how active an individual's RA is. It assesses number of tender and swollen joints (out of a total of 28), the erythrocyte sedimentation rate (ESR, a blood marker of inflammation), and the patient's 'global assessment of global health'. A higher score indicates more active disease.

****HAQ DI (Health Assessment Questionnaire – Disease Index) is a patient questionnaire that measures function and health-related quality of life through measuring a patient's ability to perform everyday tasks.

NOTES TO EDITORS: For further information on this study, or to request an interview with the study lead, please do not hesitate to contact the EULAR congress Press Office in Room N12 (opposite the exhibition hall) of the Congress Centre during EULAR 2011 or on: Email: eularpressoffice@uk.cohnwolfe.com
Rory Berrie:
Onsite tel: +44 7901 513 297
Dimple Natali:
Onsite tel: +44 7900 138 904

The European League Against Rheumatism (EULAR) is the organisation which represents the patient, health professional and scientific societies of rheumatology of all the European nations. In line with The European Union of Medical Specialists (UEMS), EULAR defines rheumatology as including rheumatic diseases of the connective tissue, locomotor and musculoskeletal systems. The aims of EULAR are to stimulate, promote, and support the research, prevention, treatment and rehabilitation of rheumatic diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with rheumatic diseases. Diseases of the bone and joints such as rheumatoid arthritis and osteoarthritis cause disability in 4-5% of the adult population and are predicted to rise as people live longer. EULAR 2011 is set to be the biggest rheumatology event in Europe with over 15,000 scientists, physicians, allied health professionals, and related audiences in attendance from over 100 countries. Over the course of the congress, almost 300 oral and more than 1600 poster abstract presentations will be featured, with 300 invited speaker lectures taking place in more than 140 sessions. To find out more about the activities of EULAR, visit: www.eular.org