The EULAR 2015 Report – Friday and Saturday Save

These abstracts and presentations were presented last week on the 12th and 13th of June at the EULAR 2015 annual meeting in Rome.

Seropositivity and Drug Responses in RA. Rheumatoid factor and CCP positivity was shown in several trials to be associated with greater responses to abatacept or tocilizumab (#FRI0178). (Editor’s note: while the association between enhanced responses and seropositivity has certainly been seen in multiple rituximab studies, the same findings in other biologics is worthy of further research. Is the lesson here that we can use this info to target who should receive non-TNF biologic agents? Or that seronegative RA patients are less likely to respond to biologic treatment with rituximab, abatacept or tocilizumab? Nevertheless, the response rates in seronegative patients is still high enough to warrant their use if clinically indicated or necessary.)

ACPA and RA Risk. Samples from the UK EPIC-Norfolk prospective population-based study (n 18,628) analyzed ACPA levels and found that ACPA positive individuals had a 2.3% (n 427). Current and former smokers had higher odds of being ACPA positive. Those who were ACPA positive were 10 times more likely to develop RA in the next 3-10 years (#OP0268).

Henoch-Schonlein Relapses. A single-center retrospective study of 417 patients diagnosed with HSP included children or young people (≤20 years) and 102 (24.5%) adults with HSP (#FRI0246). Clinical features at onset included skin lesions (55.9%), nephropathy (24%), gastrointestinal involvement (13.7%), joint symptoms (9.1%) and fever (6.2%). Joint symptoms were ultimately seen in 63% of patients. Complete recovery was seen in 83% and relapses occurred in one-third (median of 2.4 relapses). Predictors of relapse included joint manifestations at disease onset (OR 2.63), gastrointestinal manifestations during the course of the disease (1.66), and corticosteroid treatment at the time of the first episode of HSP (OR 1.65).

Calcium Supplementation and Death. A study form the Oslo RA register followed 609 since 1996 for 7414 patient years. In multivariate analyses, high baseline ESR and calcium supplementation osteoporosis were predictors of all-cause mortality and cardiovascular mortality and that both together contributed to mortality. In their cohort, DMARDs or steroid use did alter the mortality risk (#SAT0365). (Editor’s note: the cause for this association is unexplained, if not unexpected. While this has been reported before, there are other recent reports refuting the contention that calcium supplementation may increase the risk of CV events or mortality, especially in women  http://url.ie/z1d1.)

Tapering Tocilizumab in SoJIA. The Tender trial enrolled 112 systemic onset JIA (SoJIA) patients and showed the efficacy of high dose tocilizumab at 8-12 mg/kg given as an intravenous infusion every 2 weeks (#SAT0483). In the 5 year follow up of these patients, several were given the option of alternative dosing (spacing) to their infusions. At 5 years nearly half of patients dropped from the trial, but 35% (n 39) entered into a optional alternative dosing regimen wherein infusions were spaced from every 2 to every 3 and then every 4 weeks. Flares were seen in 19 of 39 patients at 1.5-25.3 months after change. Risk of losing their inactive disease was 62.5% if on MTX, 39.1% for those not on MTX. In the end only 5 patients were able to withdraw all drug therapy. (Editor's note: management of SoJIA and adult Still’s disease is difficult, especially since most will go into remission spontaneously but it is unclear if this will be in months or years. This study tells us that many will respond to IL-6 inhibition and that many will be able to stop therapy (presumeably the dropouts) but others will have to be challenged by spacing out treatment intervals or lowering the dose. The good news is that if the patient still has active inflammatory disease, the return of symptoms is usually brisk and obvious.)

Baricitinib in RA. Baricitinib is a new oral, once daily, JAK 1/2 inhibitor that has been active in drug development for patients with active RA. Two important trials were presented at EULAR, including the RA-Build trial where 684 DMARD incomplete responders were randomized to placebo or 2, 4 mg of baricitinib (#LB0001). Although the ACR20 placebo response was 40%, the baracitinib ACR20/50/70 responses were 68%, 34%, 18% at 24 weeks. Moreover, significant X-ray protection was seen with the 2 mg and 4 mg dose. In the RA-Beacon trial, 527 active RA patients, of whom 57% had received ≥2 bDMARDs and 38% had received ≥1 non-TNFi bDMARD, were treated with a DMARD and randomized to placebo or the 2 mg or 4 mg dose over 24 weeks (#OP0029). The 4 mg qd dose showed ACR 20/50/70 responses at 12 weeks of 55%, 28%, and 11% (with a PBO ACR20 of 27%). Serious infections were seen in 2-3% and there were no cases of TB, opportunistic infecions or bowel performations. There were a few cases of H. zoster. The safety profile and efficacy of this compound appears promising.