EULAR 2016 Drug Safety Report Save

The EULAR Annual European Congress of Rheumatology meeting was held in London from June 8-11, 2016 and was well attended by thousands. Notably, this year’s meeting had over 2,000 poster displays, and the EULAR 2016 Congress presented new recommendations on the management of rheumatoid arthritis, spondyloarthritis, and fibromyalgia.

The following is a collection of presented abstracts covering a variety of safety issues. These can be searched by going to the EULAR website and entering the abstract number.

Rare Colitis with Secukinumab (SEC) Clinical Trials: Schreiber et al. (OP0113) reviewed the SEC clinical development program to assess the frequency of colitis onset or exacerbation with the use of SEC. The SEC package insert warns of new onset IBD (Crohn’s and ulcerative colitis) occurring in psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients receiving SEC. In the phase 2 and 3 trials SEC involved psoriasisi (3430),  PsA (974),  and AS (571) patients with >5200 pt-yrs of drug exposure. Across all indications they found 9 UC (4 flares, 5 new onsets) and 12 Crohn’s (6 flares, 6 new onsets). The incidence of new IBD with IL-17 inhibition was similar across all indications and similar to the expected rates drawn from the literature.

Herpes Zoster and Biologics: Several abstracts addressed the problematic issue of new onset Herpes zoster in patients with autoimmune disease and with biologic therapies. The RHUMDATA Canadian database (FRI0120) showed that methotrexate (MTX) did not increase HZ rates, but that biologics doubled and steroids increased the HZ risk 6-7 fold. The IORRA Japanese RA database (FRI0146) showed that HZ was increased in RA (14.2/1000 pt-yrs) and that risk was augmented by renal disease, diabetes, steroid use – but not biologics or MTX. Yun et al. (FRI019) studied 59,627 vaccinated Medicare patients with autoimmune or inflammatory disorders and compared HZ rates  to 119,254 unvaccinated, matched AI patients and found initial protection (0.75 per 100 PY) during the first year post vaccination that increased to 1.36 during the 6th year post. Thus HZ vaccination has short term efficacy (for up to 5 years). There are no recommendations for beyond that period.

JIA Associated Malignancy: BiKeR (OP0219) is a German registry of children with juvenile idiopathic arthritis (JIA) that prospectively followed 3695 JIA patients treated with MTX and /or TNFα inhibitors. After 13198 observation years they found 12 cases of suspected malignancies, including 7 lymphoid neoplasms. The total rate of malignancies observed in the registry (0.91/1000Y) exceeded the rate compared to the German cancer registry (0.16/1000Y, p0.001). Hence, the JIA cancer risk was elevated (RR = 4.25; p0.0001) compared to the German population. The increased risks seen with MTX and biologic therapy were not different than the JIA risk without biologics. 

Tocilizumab (TCZ) Safety in the Elderly:  ICHIBAN is a prospective German registry of 902 RA patients treated with IV TCZ (FRI0202). The efficacy and safety of TCZ was assessed in those 50 yrs.; 50-65 yrs.; and >65 yrs. of age.  Efficacy was unaffected by age. There were 2 intestinal perforations (1 under 50 yrs. and 1 in the 50-65 yr. group). The rates of infections, serious infections and TCZ discontinuation rates due to an AE did not increase with age.

Disease Control Means Less Infection: Curtis reported his analysis of the CORRONA database (OP0259) looking at the influence of sustained low disease activity (LDA: CDAI 10-2.8) or sustained remission (CDAI2.8) on the risk of serious infections. They found that being in remission had no risk of SIE (Crude IR 1.03), but that LDA was associated with a modest increase in SIE (IR 1.92; 1.68-2.19) and that moderate or high disease activity had the highest risk of SIE (IR 2.51; 2.23-2.82). 

Rituximab Registry Shows No Increase in Malignancies: SUNSTONE is a prospective registry, started in 2007, of 989 RA patients on rituximab. With over 3 years of follow-up (3844 pt-yrs), the found 17 malignancies occurring. These were largely solid tumors (breast, lung, colon, skin, melanoma) and there were no new lymphomas. The observed malignancy event rate was 0.44 per 100 person years (this compares well to the product label that quotes the risk of incident malignancy with RTX is 0.74 per 100 person years).