Tofacitinib at the EULAR 2014 Meeting in Paris

Tofacitinib (Xeljanz®) had a negative opinion for marketing authorization in Europe by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) about a year ago. The issueas had been: an insufficient demonstration of a consistent reduction in disease activity and structural damage to joints; moreover the CHMP had also been concerned about serious infections, gastrointestinal perforations, and malignancies as observed in studies.

At the EULAR 2014 Meeting in Paris tofacitinib has been present in quite a lot of studies. These studies show the commitment of the company to get tofacitinib approved in Europe. I'll show the studies at the end of this blogpost.

[THU0131]

K. Katayama and colleagues presented: "LONG TERM RESULTS OF INHIBITION OF RADIOGRAPHIC JOINT DAMAGE PROGRESSION IN SMALL AND MEDIUM AND LARGE JOINTS IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH TOFACITINIB MONOTHERAPY". Conclusions: "Progression of small and M-L sized joints were effectively inhibited by tofacitinive mono-therapy." The study shows 4 year data, but only for N=8.

[THU0143]

M. Lamba and colleagues looked at: "PHARMACOKINETICS, BIOAVAILABILITY AND SAFETY OF A MODIFIED RELEASE ONCE DAILY FORMULATION OF TOFACITINIB IN HEALTHY VOLUNTEERS". Conclusions: "This study demonstrates the single dose equivalence of AUCinf

and Cmax of the MR and IR formulations of tofacitinib. Single doses of both formulations were well tolerated. This novel MR formulation of tofacitinib facilitates an opportunity to enable QD dosing, while maintaining systemic drug concentrations similar to the IR formulation (administered BID)." As N=26 isn't adequately powered: "Multiple-dose studies will be conducted to confirm the predictions of the SS PK profile and demonstrate equivalence between formulations following SS dosing."

We don't know if the studies to demonstrate a consistent reduction in disease activity and structural damage to joints have come so dar to be published soon. But we know, that we have at least another year to wait for tofacitinib (Xeljanz®).

Links:
Xeljanz® (tofacitinib) and the Negative Opinion for Marketing Authorization in Europe http://rheumatologe.blogspot.de/2013/04/xeljanz-tofacitinib-and-negative.html
My statement on tofacitinib after EULAR 2012: http://rheumatologe.blogspot.de/2012/07/tofacitinib-oral-jak-inhibitor-at-eular.html

Here are the titles an Abstract numbers of the other studies on for tofacitinib (Xeljanz®):

[OP0152] EFFECTS OF TOFACITINIB MONOTHERAPY VERSUS METHOTREXATE ON PATIENT-REPORTED OUTCOMES IN THE 2-YEAR PHASE 3 ORAL START TRIAL IN METHOTREXATE-NAIVE PATIENTS WITH RHEUMATOID ARTHRITIS

[OP0154] INTEGRATED SAFETY ANALYSIS OF TOFACITINIB IN RA CLINICAL TRIALS WITH A CUMULATIVE EXPOSURE OF 12,664 PATIENT-YEARS

[THU0126] EVALUATION OF THE EFFECT OF TOFACITINIB ON MEASURED GLOMERULAR FILTRATION RATE IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS

[THU0145] ASSOCIATION OF MEAN CHANGES IN LABORATORY SAFETY PARAMETERS WITH C-REACTIVE PROTEIN AT BASELINE AND WEEK 12 IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TOFACITINIB

[THU0147] TOFACITINIB, AN ORAL JANUS KINASE INHIBITOR: ANALYSIS OF MALIGNANCIES ACROSS THE RHEUMATOID ARTHRITIS CLINICAL PROGRAMME

[THU0148] TOFACITINIB, AN ORAL JANUS KINASE INHIBITOR: ANALYSIS OF MALIGNANCIES IN JAPANESE PATIENTS ACROSS THE RHEUMATOID ARTHRITIS CLINICAL PROGRAMME

[FRI0178] ESTIMATED MEDICAL EXPENDITURES AMONG PATIENTS WITH RHEUMATOID ARTHRITIS UNDERGOING TREATMENT WITH TOFACITINIB, AN ORAL JANUS KINASE INHIBITOR

[FRI0333] EFFECTS OF TOFACITINIB TREATMENT ON LEPTIN AND OTHER COMPONENTS OF THE MULTI-BIOMARKER DISEASE ACTIVITY SCORE IN PATIENTS WITH RHEUMATOID ARTHRITIS

[AB0089] TOFACITINIB MEDIATES SYNOVIAL ANGIOGENESIS IN PSORIATIC ARTHRITIS

[AB0463] TOFACITINIB IMPROVES ARTERIAL STIFFNESS WITH METHOTREXATE-RESISTANT ACTIVE RHEUMATOID ARTHRITIS. A COHORT STUDY

[AB0474] CHANGES IN T AND B LYMPHOCYTE SUBSETS WITH TOFACITINIB DO NOT TRANSLATE FROM NONCLINICAL SPECIES TO HUMANS

[AB1057] CONTEXTUALISATION OF SAFETY ENDPOINTS IN THE TOFACITINIB RHEUMATOID ARTHRITIS (RA) DEVELOPMENT PROGRAMME: COLLABORATION WITH THE CONSORTIUM OF RHEUMATOLOGY RESEARCHERS OF NORTH AMERICA (CORRONA) REGISTRY