Thursday 10 December 2015

Updates from ACR 2015 San Franscisco




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.



Sunday 15 November 2015

Updates from the American College of Rheumatology (ACR) Scientific Congress, San Francisco, 2015


Updates from ACR Scientific Congress, San Francisco, 2015

I attended the ACR Scientific Congress in San Francisco from 6-11 November 2015. This was an opportunity to share, discuss and exchange information on topics and subjects in rheumatology.

I will be sharing with you my notes from the ACR Scientific Meeting so watch this space! 

Thanks for following my tweets @synovialjoints during the ACR.

Moscone Centre, San Francisco

Meeting international colleagues at the ACR
Great discussion and sharing of knowledge with colleagues

Thursday 28 May 2015

Reflections from British Society for Rheumatology Conference 2015



Reflections from the British Society for Rheumatology Conference 2015, Manchester UK

      I had the privilege of attending the recent British Society for Rheumatology AGM in Manchester, UK from the 28th -30th April. It was a privilege as this was the first time in 5 years that I was able to attend the whole conference. In years past, I had the responsibility of looking after the ward and department. So, this year was my turn to attend and I was looking forward to the attending UK's premier rheumatology gathering.
    As soon as the train passed Stockport, the weather changed from the Berkshire sunshine to the Lancashire grey and wet. I had forgotten to bring my raincoat and umbrella! Soon I was at the conference centre, all warm and dosed up with caffeine from the exhibition booths.

Manchester Central - venue for BSR 2015
          It was nice meeting up with colleagues from far and wide, sharing and discussing all things in and out of rheumatology. One of the first delegates I met was Martin Lau @ImpactSports9 . It was good to meet him in person, our previous contact was on twitter.

With Martin Lau @ImpactSports9

          The BSR 2015 app was helpful in planning the day at the conference. After poster viewing on the first morning, I attended the session on optimising service to RA patients. A very relevant session in the current NHS climate where the challenge is to deliver the best service with finite resources.


         After lunch, the next session was aptly named Jewels in the Crown. The keynote address was from Sir Mark Walport who gave an excellent review of how future healthcare will be shaped.


          This was followed by the prestigious Heberden Round which was delivered by Prof. David D'Cruz. The lecture was titled Lupus and the art of clinical medicine. The lecture kept to the high standards and tradition of William Heberden (1710 –1801), a distinguished physician.



          There was a lot of new information on the use of technology including apps and software that could be used in clinical practice. More work needs to be done to see how applicable these technologies will be. The day ended with a session on the use of such technologies and if they may break boundaries in RA care.



        The second day started with poster viewing and then the session on essentials in rheumatology. This was a session on disease assessment and management. A very practical and useful session.


        A quick dose of coffee was then followed by viewing of posters on the spondyloarthropathies. Lots on new initiatives in the area which is really exciting. The next three sessions were focused on infection,  autoimmunity and the role of the microbiome in inflammatory arthritis.



       In the afternoon, it was the turn of the second of the Heberden presentations. The Herberden Oration was presented by Prof. David Scott. A tremendous presentation on the excellent work through the years to improve RA outcomes.


         The day was finished on the high at the Conference dinner held at Old Trafford, the home to Manchester United. I took the pre-dinner stadium tour and got the see the Theatre of Dreams in a little more detail. The highlight was visiting the home team changing room and walking down to tunnel leading to the arena. We were entertained by an after dinner speech by ex-Red Devil star, Norman Whiteside.

The Theatre of Dreams

With Norman Whiteside
             The final day of the conference started with poster viewing. The next few sessions were very clinical, focusing on clinical guidelines, management and use of biologic treatments.



        Finally, to round up the conference, I chaired the Spondyloarthritis Special Interest Group Meeting. This was the last session at the conference and I was encouraged that 80 attended! We even had the main auditorium for the meeting. The speakers did an excellent job updating us on topics relevant to the area of spondyloarthritis.

          I came away from the meeting with new information that will be shared with the team as we deliver our service to patients. It was a well organised meeting and an opportunity to share and exchange information with fellow rheumatologists. I look forward to BSR Glasgow 2016.





Sunday 1 February 2015

The Rheumatology Voice - increasing arthritis awareness



Increasing Arthritis Awareness

Initiatives in 2014 to increase Arthritis Awareness


            The NHS landscape changed with the creation of the Health and Social Care Act 2012. This means the greater need for collaboration between GPs, specialists and patients. Together, the aim is for new care pathways that deliver benefit to patients. In arthritis, key to the success of the care pathway is the early recognition of arthritis. This is done by increasing awareness of arthritis.

The benefits of increased awareness include earlier recognition, diagnosis, referral and treatment of a potentially painful and disabling condition. Earlier diagnosis and treatment will lead to better outcomes.

All of this work would not have been possible without the help of members of my rheumatology unit and the teams involved in the many events in 2014.  This includes patient groups who have been very supportive of the drive to increase arthritis awareness.

            Over 2014, my department hosted GP events that focused on topics that included early inflammatory arthritis, polymyalgia rheumatica, osteoporosis, gout and the spondyloarthropathies. This was geared for colleagues in primary care, to increase awareness and improve referral to specialists. It is important to approach this from the perspective of GPs. A recent posting by Paula Wright in the BMJ has been helpful http://careers.bmj.com/careers/advice/advice-overview.html

            In May, I chaired an Inflammatory Back Pain (IBP) seminar for GPs, nurses and physiotherapists. This is to increase awareness of IBP which is a feature of ankylosing spondylitis (AS). The message is that not all back is the same. Early detection of AS will improve long term outcomes.


With the team at the Back Pain Seminar


            In July, there was public engagement with the ‘Don’t Turn Your Back On It’ campaign. This initiative was supported by the National Ankylosing Spondylitis Society (NASS). The team spoke to many people in Reading Town Centre on inflammatory back pain. There were acrobats to highlight the event on the day.

With Sue Hicks, Specialist Physiotherapist in Reading Town Centre


            In October, the Reading Fibromyalgia Society held their first anniversary celebration at Prospect Park Hospital in Reading. I and other members of the Rheumatology Team were able to support this. The event was attended by Alok Sharma, MP for Reading West and also by Cllr. Sarah Hacker, Reading Deputy Mayor. See their blogs on this event:




            In November, two seminars were held to increase awareness of arthritis. A public seminar was organised by the Royal Berkshire Hospital for members on early arthritis and rheumatoid arthritis. The event was also attended by the National Rheumatoid Arthritis Society (NRAS) http://www.nras.org.uk/

With the NRAS at the Trust Public Seminar on rheumatoid arthritis

            In the same month, there was a GP teaching event on topics such as early referral to specialists, what to look out for, how to manage arthritis in primary care. There was also a practical session on how to perform the disease activity score 28 (DAS28), an outcome measure used in rheumatoid arthritis. We were supported by our local arthritis charity, Arthritis Matters for this event http://www.arthritismattersreading.co.uk/


GP Teaching event to increase awareness of arthritis

            November was a busy month as it was also the month that the National Ankylosing Spondylitis Society (NASS) organised the parliamentary event to raise awareness of the need to increase access to physiotherapy. This is the next step of the NASS As It Is campaign http://nass.co.uk/news/as-it-is---next-steps-in-the-campaign/?keywords=as+it+is


With Debbie Cook, NASS Director
At the NASS event with the team from Portsmouth

            In 2015, more such events are planned to continue the drive to increase awareness of arthritis. Rheumatology needs a voice and together, our efforts no matter how small or big, will go towards improving patient access and care. This is A Joint Venture.

@synovialjoints

Views are my own. These are opinions, not specific medical advice and cannot replace the need to see your physician for review of your individual medical condition.