I enjoy attending the American College of Rheumatology (ACR) meeting. It is a chance to meet and discuss with colleagues from across the world on topics of interest in rheumatology.
Since returning from the ACR 2015, I've shared my highlights with my team. This was through our Journal Club. It takes about 60 minutes to cover a session.
Here are some of my highlights from ACR 2015. I hope you may find it useful to discuss in your Journal Club or educational meetings.
You can find further details of the presentations and abstracts at the ACR 2015 website:
http://acrabstracts.org/meetings/2015-acrarhp-annual-meeting
1. IL-17 inhibition in Ankylosing Spondylitis
There were many presentations covering this topic at ACR 2015.
The posters that covered this topic were #2887, #2890,
#2896, #974, #981, #6L,
Secukinumab in AS,
52 week study #2890 (Baeten D et al)
Secukinumab is an anti-IL17A mAb
used to treat AS. Data from MEASURE 1 and MEASURE 2 were analysed. Secukinumab
vs placebo. Included anti TNF-naïve and anti-TNF IR (not more than one anti-TNF).
ASAS 40 response at Week 52 was measured. The
outcome in different groups were:
10mg/kg IV 0,2,4 weeks to 150mg sc every 4 weeks
Anti-TNF
naïve 67.1%, Anti-TNF IR 45.8%
10mg/kg IV 0,2,4 weeks to 75mg sc every 4 weeks
Anti-TNF
naïve 48.8%, Anti-TNF IR 50.0%
150mg sc Week 0,1,2,3 and q4w
Anti- TNF
naïve 64.1%, Anti-TNF IR 45.5%
75mg sc Week 0,1,2,3 and q4w
Anti-TNF naïve
47.6%, Anti-TNF IR 26.3%
Response was better in the anti
TNF naïve group. There was no incremental increase in efficacy conferred by the
initial iv loading. Secukinumab 150mg sc provides sustained improvement of AS
both anti-TNF naïve and IR patients.
Safety and Tolerability, 52 week results #2887 (Deodhar et al)
Secukinumab was well tolerated in
patients with active AS with a low incidence of AE/SAE (65.7/3.3% in
Secukinumab and 58.7/4.1% in placebo groups).
Nasopharyngitis was the commonest
AE with secukinumab (11.2% vs 6.1% in placebo).
Discontinuation due to AE was
4.7% in Secukinumab and 5.6% in placebo. 3 deaths (1 suicide in placebo, 1
respiratory failure and 1 acute MI in secukinumab group)
Secukinumab in AS, 104 week results #2896
(Baeten D et al)
The data from 104 weeks showed
sustained response to
10mg/kg IV 0,2,4 weeks to 150mg sc every 4
weeks
ASAS 20/40 was 79.3/64.4%
In anti-TNF naïve, ASAS 20/40 was
85.5/69.6%
In anti-TNR IR, ASAS 20/40 was
55.6/44.4%
10mg/kg IV 0,2,4 weeks to 75mg sc every 4 weeks
ASAS 20/40 was 72.1/53.5%
In anti-TNF naïve, ASAS 20/40 was
72.3/52.3%
In anti-TNF IR, ASAS 20/40 was
71.4%/57.1%
Effects of
Secukinumab on Radiographic Progression, 2 year data #6L (Baraliakos, X et al)
Study on radiographic progression in patients with active
AS, phase 3 study with Secukinumab. Data from MEASURE 1 was analysed. Lateral
radiographs of cervical and lumbar spine were performed at baseline and Week
104 and the mSASSS score used.
Patients received a loading dose at baseline Wk 0, 2, 4 then 150mg sc or 75mg
sc every 4 weeks.Placebo patients switched to Secukinumab at Wk 16 (if ASAS20
non-responder) and at Wk 24 (if ASAS20 responder).
Secukinumab data was pooled and
compared against the placebo group. There was no major difference between the
secukinumab only group (mSASSS 0.30 ±
2.53) compared to the placebo group in terms of mSASSS change through week 104.
80% of patients on Secukinumab did not show radiographic progression. Factors
predicting radiographic progression were baseline syndesmophytes, male gender
and elevated CRP at baseline. This showed IL-17A inhibition on structural
change in AS.
2. IL-17 inhibition in Psoriatic Arthritis
1.
Ixekizumab
in PsA, Phase 3 , 24 week Study, #977
(Mease P et al)
Ixekizumab, an IgG4
anti-IL17A mAb was studied in psoriatic
arthritis (PsA).
Biologic naïve patients, receiving Ixekizumab 80mg q2w or q4w
vs Adalimumab 40mg q2w vs placebo.
ACR 20/50/70 response at 24
weeks were:
Placebo 30.2 / 15.1 /
5.7 %
Adalimumab 57.4 / 38.6 / 17.8 %
Ixekizumab 80mg q2w 62.1 / 46.6 / 34.0 %
Ixekizumab 80mg q4w 57.9 / 40.2 / 23.4 %
There was also
improvement in skin scores PASI 75/90/100 responses compared to placebo at
weeks 12 and 24. There were greater adverse events in the Ixekizumab and
Adalimumab groups compared to placebo.
Discontinuation due to treatment
emergent adverse events was similar across groups and no deaths occurred. Ixekizumab
showed significant, clinically meaningful improvement in psoriatic arthritis.
2. Ixekizumab
in biologic naïve PsA – effects on QOL, function, work # 2145 (Gottlieb A et
al)
Ixekizumab
improved QOL, physical function, work productivity in biologic DMARD-naïve
patients (HAQ-DI, SF-36, EQ-5D, WPAI)with active PsA.
3.
IFNa in SLE
Phase 2 study, 48 week study #3223 (Furie R et al)
Anifrolumab,
an IFNa receptor MAb was studied in moderate SLE. N=305. Patients were randomized to receive
Anifrolumab IV 300mg or 1000mg every 4 weeks for 48 weeks vs placebo.
The SLE
Responder Index (SRI) was used as the outcome measure together with reduction in
oral corticosteroid (OCS) use at days 169 and 365. The groups were divided by IFN gene signature (IFN high vs IFN low).
A greater proportion of Anifrolumab treated
patients (300mg: 34.3%, 1000mg: 28.8%) vs placebo (17.6%) at day 169 and
continued to day 365 (300mg: 51.5%, 1000mg 38.5%) vs placebo (25.5%).
Anifrolumab efficacy was similar or better in the IFN high patients. The lack
of dose response is due to nearly
similar degress of IFN gene signature inhibition with two Anifrolumab doses.
There was a
higher frequency of influenza and herpes zoster in the Anifrolumab arms. This
study shows promise for IFNa inhibition in the treatment of SLE.
4.
Rituximab, new biomarker to predict relapse?
Use of CD4+ T cells
for monitoring #1656 (Lavielle M et al)
CD4+ T cells
are depleted of a first cycle on rituximab (RTX) in patients with RA. This
effect was seen in responders to RTX. This raises the possibility that CD4+ T
cells levels may be linked to disease activity post RTX treatment.
Post
treatment, RTX-induced CD4 T cell depletion was temporary and was followed by
normalization of counts to the pre-treatment level. In comparison, B cells
counts remain low when patients were re-treated. Patients who did not respond
to the first cycle of RTX showed only a small decrease in CD4+ T cell levels.
Those who had a high depletion of CD4+ T cells (> 33%) in the second cycle
were more likely to respond. 80% of
those who responded had greater CD4+ T cell depletion in the second cycle
compared to the first.
This study
shows CD4+ T cell levels depletion occurs over successive cycles of RTX. CD4+ T
cell levels are related to changes in disease activity more than B cells which
remain depleted.
Monitoring CD4+ T cells may be a useful biomarker to assess
response to RTX, disease activity and further evaluation of treatment efficacy
and re-treatment intervals of RTX.
5.
JAK kinases in RA
Baricitinib in RA, Phase 3 study against placebo and adalimumab #2L (Taylor P et al)
Baricitinib
(bari) is an oral JAK 1 and JAK 2 inhibitor. This is a Phase 3 study, placebo
(PBO) controlled trial,
reporting the 24 wk results of a 52 wk study in MTX inadequate responders (IR).
Patients
with active RA(TJC>6, SJC>6, hsCRP>6mg/L) were randomized to PBO, bari
4mg od, or adalimumab (ADA) 40mg every 2
weeks (Q2W).
The primary endpoint was
ACR 20 response at Wk 12 for bari
vs PBO. At Wk 12, the ACR 20/50/70 response for PBO was 40/17/5% respectively and for bari 70/45/19% respectively. At Wks 12
and 24 there were improvement in ACR 20/50/70
for bari vs PBO.
Compared
to ADA, bari was superior with respect to ACR 20 at Wk 12 (bari 70 vs ADA 61) and DAS28-CRP. Compared to PBO,
serious adverse events rates were similar for bari and lower for ADA. Serious infection rates were
similar across groups.
Baricitinib
is a treatment option in active RA despite background MTX with significant
clinical improvements compared to
PBO and ADA. There was acceptable safety and tolerability.
6.
IL-6 inhibition in Giant Cell
Arteritis
There were reports on the use of
Tocilzumab in
GCA #1979, #1980.
#3142, #1L
PMR #1986, #1987,
#1985
Tocilizumab in GCA #1980 (Regent A et al)
Tocilizumab (TCZ) is a humanized
IgG1k mAb against IL-6 receptor and was studied in the treatment of GCA. N=34 patients were included.
TCZ 8mg/kg monthly + GC vs
Placebo + GC
Week 12 remission rates in TCZ vs
placebo groups were 85% vs 40%
Week 52 no relapse in TCZ vs
placebo groups were 85% vs 20%
TCZ is beneficial
for induction and maintenance
therapy in GCA
GiACTA Study #1979 (Tuckwell et al)
TCZ and T Regs in GCA #3142 (Unizony S et al)
TCZ treated patients had higher frequency of
Tregs compared to placebo (1.3% vs 0.6%)
7.
ANA negative, ENA positive, clinical
relevance ?
Krause ML et al #773
ANA + ENA testing in a single
centre
ANA –ve 79%, ENA +ve 6.8% (of
this 96% were a single ENA positive)
Anti-RNP was the commonest (54%)
followed by anti –Ro (19%) , anti-La (16%) and Scl-70
(14%). Sm and Jo-1 were
rare.
ANA negative but positive ENA is rare and
uncommon to have connective tissue disease.
8.
Ultrasound in Giant Cell Arteritis
TABUL USS vs TAB, role of ultrasound compared to TAB (Luqmani et al) #2160
TAB typically negative in 10-30%
of true cases
Sensitivity of biopsy / USS 39% / 54%
Specificity of biopsy / USS 100% / 81%
USS + clinical judgement - sensitivity 93%, specificity 77%
Biopsy + clinical judgement –
sensitivity 91%, specificity 81%
USS for all suspected cases
followed by biopsy in medium to high risk patients with negative USS was cost
effective (sensitivity 95%, specificity 77%)
9.
Videocapsule (VCE) endoscopy in SPA
Uncovering Crohn’s Disease in SpA (Seidman
E et al) #2061
SpA and Crohn’s clinical
association 5-15%, colonoscopy 33%
Significant small bowel
inflammation by VCE 41% vs colonoscopy 13.1%
Correlated with elevated faecal
calprotectin but not clinical features or raised CRP
10.
Scleroderma lung study
SLSII Oral CYC and MMF in ILD (Clements
PJ et al) #1075
Oral CYC 2mg/kg/day for 1 year
followed by placebo in year 2
MMF 1.5g bd for 2 years
Slightly higher modified Rodnan
skin scoring (MRSS) higher in MMF group at baseline
At 24 months
FVC improvement in MMF 1.86 vs
CYC 2.24
MRSS decline in MMF 2.9 vs CYC
6.1
More premature withdrawal of CYC
– weight loss, leucopenia, thrombocytopenia
MMF vs CYC – comparable and both
efficacious in treating SSc-ILD
I hope you will find this useful for review and discussion @synovialjoints
These are results from studies and not medical advice. Views are my own. This cannot be taken as specific medical advice and cannot replace the need to see your physician if needed for review.
