Wednesday, 1 November 2017

NICE Guidelines on Spondyloarthritis - a guide for GPs and referrers


The NICE Guidelines on Spondyloarthritis – A guide for GPs and referrers

Dr. Antoni Chan, PhD FRCP
Consultant Rheumatologist, Royal Berkshire Hospital and Spire Dunedin Hospital, Reading

A summary of the National Institute for Health and Care Excellence. Spondyloarthritis in over 16s: diagnosis and management (NICE guideline NG65) 2017. www.nice.org.uk/guidance/ng65.

Background

The spondyloarthropathies (SpAs) encompasses a group of inflammatory conditions with shared features. These include extra-articular manifestations such as iritis, colitis and psoriasis. The SpAs can be divided into:

Axial (spinal) spondyloarthritis
  • Non-radiographic axial spondyloarthritis (positive MRI, negative X-ray for sacroilitis)
  • Radiographic axial spondyloarthritis (also called Ankylosing Spondylitis)
Peripheral spondyloarthritis
  • Psoriatic Arthritis (arthritis related to skin psoriasis)
  • Reactive Arthritis (arthritis occurring after gastrointestinal or genitourinary infection)
  • Enteropathic Arthritis (arthritis related to Ulcerative or Crohn’s colitis)
The clinical manifestations of spondyloarthritis include
  • Enthesitis – inflammation at sites of tendon insertion in the bone eg. Achilles tendon
  • Dactylitis – inflammation of the whole digit giving ‘sausage’ like appearance
  • Acute anterior uveitis
When to suspect SpA and refer to rheumatologist?
  • Presence of inflammatory low back pain before the age of 45 years and has lasted for more than 3 months
  • Low back pain that improves with movement and worse with rest
  • Alternating buttock pain
  • Waking during the second half of the night due to symptoms
  • Improvement within 48 hours of taking NSAIDs
  • Current or previous arthritis (swelling, tenderness of joints)
  • Current or previous enthesitis
  • Current or previous dactylitis
  • Current or previous psoriasis
  • First degree relative with spondyloarthritis
If 4 or more of these clinical features are present please refer.
If 3 clinical features are present, check the HLA- B27 blood test and refer.
If 2 or fewer clinical features are present, advise repeat assessment if new signs or symptoms related to SpAs develop

What further tests can be done by a rheumatologist after referral?
  • X-ray of sacroiliac joint
  • MRI of whole spine and sacroiliac joints
  • Inflammatory markers (ESR, CRP)
  • HLA-B27
What treatments are available?
  • Physiotherapy
  • Injections
  • Clinical Psychology
  • Occupational Therapy
  • NSAIDs
  • Disease modifying drugs (DMARDs)`
  • Anti-TNF (biologics)
  • Secukinumab (biologic)
GPs and referrers can refer to their local rheumatology departments for suspected AS or SpA.


There is a dedicated Ankylosing Spondylitis clinic at the Royal Berkshire Hospital, Reading (NHS) and Spire Dunedin Hospital, Reading (private). Dr. Chan runs both clinics with physiotherapists.

Sunday, 15 January 2017

My Rheumatology Highlights 2016


My Rheumatology highlights from 2016

As we start the new year 2017, here are my rheumatology highlights from papers and abstracts in 2016. These were papers and abstracts in no particular order. I discussed these papers with colleagues at conferences, meetings and journal clubs. I hope you find them useful. 

They were many other papers but due to space and time, I have not included all of them here. 

Do share your favourite rheumatology papers from 2016 too.

Baricitinib in Patients with Refractory Rheumatoid Arthritis.
N Engl J Med. 2016 Mar 31;374(13):1243-52
Phase 3 study involving 527 patients with an inadequate response to or unacceptable side effects associated with one or more tumor necrosis factor inhibitors, other biologic DMARDs, or both, we randomly assigned the patients in a 1:1:1 ratio to baricitinib at a dose of 2 or 4 mg daily or placebo for 24 weeks. Significantly more patients receiving baricitinib at the 4 -mg dose than those receiving placebo had an ACR20 response at week 12 (55% vs. 27%, P<0.001). In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs, baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks.

Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study.
Ann Rheum Dis. 2016 Nov;75(11):1909-1916.
The efficacy and safety of sifalimumab were assessed in a phase IIb, randomised, double-blind, placebo-controlled studyof adults with moderate to severe active systemic lupus erythematosus (SLE). Compared with placebo, a greater percentage of patients who received sifalimumab (all dosages) met the primary end point of SLE responder index response at week 52 (placebo: 45.4%; 200 mg: 58.3%; 600 mg: 56.5%; 1200 mg 59.8%). Sifalimumab is a promising treatment for adults with SLE. Improvement was consistent across various clinical end points, including global and organ-specific measures of disease activity.

Efficacy and Safety of Switching Between Certolizumab Pegol and Adalimumab after Primary Anti-TNF Treatment Failure: 2-Year Results from a Randomized, Investigator-Blind, Superiority Head-to-Head Study

ACR ABSTRACT NUMBER: 602
Fleischmann R et al
EXXELERATE is the first randomized controlled trial (RCT) to address immediate switching to another TNFi, in a TNFi IR patient population. EXXELERATE was a 104-wk randomized, investigator-blind, parallel-group, head-to-head superiority study comparing the early (Wk 12)- and Wk 104 efficacy and safety of certolizumab pegol (CZP)+MTX vs adalimumab (ADA)+MTX. Pts were randomized 1:1 to CZP+MTX or ADA+MTX. Clinical improvement was observed in a considerable proportion of pts; 33 pts (55.9%) switching to CZP and 40 pts (60.6%) switching to ADA responded 12 wks later (Wk 24) by achieving DAS28(ESR) ≤3.2 or a DAS28(ESR) reduction from Wk 12 of ≥1.2. EXXELERATE demonstrated that efficacy can be achieved using a second TNFi in a proven primary TNFi failure pt population.

Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions.
Ann Rheum Dis. 2016 Aug;75(8):1428-37
Schett G et al
This review article discusses the current developments of DMARD tapering and provides an overview of existing studies on this topic and addresses new strategies to reach drug-free remission. Defining patients eligible for DMARD tapering are described and potential future strategies in using biomarkers in predicting the risk for disease relapse after initiation of DMARD tapering are addressed.

Efficacy and Safety of Tocilizumab in Patients with Giant Cell Arteritis: Primary and Secondary Outcomes from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial

ACR 2016 ABSTRACT NUMBER: 911
Stone JH et al
The early results of GiACTA study confirm the efficacy of tocilizumab (TCZ) in giant cell arteritis. TCZ with a 26-week prednisone taper was superior to both short- and long-course prednisone tapers for the achievement of sustained remission at 52 weeks. The addition of TCZ to prednisone also led to a substantial reduction in the cumulative prednisone doses required to control GCA.

Combination Therapy of Apremilast and Biologic Agent As a Safe Option of Psoriatic Arthritis and Psoriasis

ACR ABSTRACT NUMBER: 1725
Metyas et al
Apremilast can be safely and effectively combined with biologic agents in patients with plaque psoriasis or psoriatic arthritis not responding adequately to these agents alone. No major side effects of cancer or sever infection were reported other than nausea and/or vomiting that were manageable in some patients.

No Increased Risk of Inflammatory Bowel Disease Among Secukinumab-Treated Patients with Moderate to Severe Psoriasis, Psoriatic Arthritis, or Ankylosing Spondylitis: Data from 14 Phase 2 and Phase 3 Clinical Studies

ACR ABSTRACT NUMBER: 962
Deodhar A et al
Events of CD and UC in the 14 clinical studies were reported infrequently in secukinumab-treated pts with psoriasis, PsA, or AS; rates were similar across the psoriasis and PsA cohorts. EAIR rates of CD and UC observed in secukinumab-treated pts are consistent with those reported in the literature in psoriasis, PsA, and AS populations.

A Single Infusion of Rituximab Delays the Onset of Arthritis in Subjects at High Risk of Developing RA

ACR 2016 ABSTRACT NUMBER: 3028
Gerlag DM et al
The PRAIRI study reporting preliminary data from a randomized, blinded study of 81 participants. When given to individuals with preclinical RA (elevated antibodies to citrullinated proteins and rheumatoid factor but no synovitis on baseline examination), a single infusion of 1000 mg rituximab significantly delays the development of arthritis in subjects at risk of developing RA by about 12 months.

 

Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis

N Engl J Med. 2016 Dec 29;375(26):2519-29
Nissen SE et al
The cardiovascular safety of celecoxib was compared with nonselective nonsteroidal antiinflammatory drugs (NSAIDs). At moderate doses, celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety.

Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease.
N Engl J Med. 2016 Nov 17;375(20):1946-1960
Feagan BG et al.                            
Patients received a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. Patients with moderately to severely active Crohn's disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy.

Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): an open-label, randomised controlled, non-inferiority, trial

Lancet2016; 388: 239-247

Porter D et al
Data from the Optimal Management of Rheumatoid Arthritis Patients Requiring Biologic Therapy (ORBIT) study showed that initial treatment with rituximab is non-inferior to initial TNF inhibitor treatment in patients seropositive for rheumatoid arthritis and naive to treatment with biologicals, and is cost saving over 12 months.

BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids.

Rheumatology (Oxford). 2016 Sep;55(9):1693-7

Flint J et al

Updated guidelines on prescribing DMARDs and biologics in pregnancy and breastfeeding. A very useful resource for clinicians.

 

 




Tuesday, 8 November 2016

Update and highlights from EULAR Congress 2016 London

Update and highlights from EULAR 2016
I attended the European League Against Rheumatism (EULAR) Annual Congress in June 2016. This was held on home ground in London. This annual meeting brings together rheumatologists and allied health professionals from across the world.

There was a tweet up at EULAR 2016 and it was good meeting up face to face with colleagues and friends.
EULAR 2016 at the Excel Centre, London, UK

There were many abstracts presented at the meeting. See the EULAR website for the link to the abstracts.
Post EULAR, I have led a journal club and presented my highlights from the sessions at the conference. The following abstracts were my highlights of the meeting. You may wish to have a discussion with your team using these or other abstracts.
THU0058 (Tweehuysen L et al) – A systematic review looking at predictors of successful dose reduction or discontinuation of biologics in patients with RA. Over 3000 non-duplicate articles were included and biomarkers reviewed. Three predictors were identified for prediction of successful dose reduction and successful discontinuation of a biologic. These were higher adalimumab trough level for successful dose reduction; and lower Sharp/van der Heijde erosion score and shorter symptom duration at the start of a biologic for successful discontinuation.
OP0225 (Glintborg B et al) – Results from the Danish (DANBIO) registry showed that for patients with inflammatory arthritis (647 patients, 50% had RA and the other 50% were AS or PsA), a non-medical switch from infliximab (Remicade) to the biosimilar (Remsima) did not appear affect disease activity or risk of having a flare. This was up to 3 months and longer follow up will be interesting to assess this switch.
OP0182 (Gerlag D et al) – Results from the PRAIRI study (81 patients included) showed a single infusion of anti-CD20 antibody rituximab can delay the onset of rheumatoid arthritis for up to 1 year in individuals at risk of developing the condition. The participants have CCP and RF positivity, raised CRP and subclinical synovitis on ultrasound or MRI of hands.
OP0001 (Braun J et al) – Results from the MEASURE 1 trial looking at the radiographic change with the use of interleukin-17A inhibitor Secukinumab in ankylosing spondylitis. Secukinumab (both 75mg and 150mg doses) resulted in no radiographic progression in approximately 80% of patients over 104 weeks.
THU0158 (Frisell T et al) – The effect of baseline characteristics in channelling the choice of the second biologic after first anti-TNF failure in RA. Data from the Swedish Rheumatology Register from 2010-2012. The most common biologic after initial TNFi therapy were rituximab and etanercept. Those initiating a second TNFi were slightly younger, less often rheumatoid factor (RF) positive, and had slightly lower DAS28 than those initiating a non-TNFi biologic. Initiators of rituximab had longest disease duration, highest proportion RF+ and with history of malignancy or COPD, while etanercept-initiators had the lowest proportion with history of malignancy. Those initiating a second TNFi had more often switched due to adverse events.
OP0002 (van der Heijde D et al) – Results from the phase 2 study of the oral Janus kinase (JAK) inhibitor tofacitinib in ankylosing spondylitis. In this placebo-controlled double-blind study, the dose-response, efficacy and safety were evaluated. Patients were randomised to placebo, 2mg bd, 5mg bd and 10mg bd for 12 weeks. ASAS20 was achieved in 40.1%, 56.0%, 63.0%, 67.4% respectively. BASDAI50 was achieved in 23.5%, 46.2%, 42.3%, 42.3% respectively. There was no difference in the safety profile between any of the tofacitinib groups and the placebo group.
FRI0154 (Serhal L et al) – Looks at the effect on disease activity and function with failed anti-TNF dose reduction in rheumatoid arthritis. RA patients who failed dose reduction had higher DAS28 than those who were successful despite reintroduction of a standard dose of anti-TNF. Failed dose reduction did not appear to cause loss of functional capacity (HAQ) or a greater cumulative exposure to inflammation (AUCCRP) compared to successful reduction. The functional capacity (HAQ) at anti-TNF initiation appears to predict the likelihood of successful dose reduction. Non-reducers had a higher HAQ score (1.59) compared to failed dose reduction (1.28) and successful dose reduction (0.95). Following dose re-escalation, 32% had achieved DAS28 remission, 20% developed lower (LDA), 44% moderate (MDA) and 4% severe disease activity (SDA).
FRI0155 (Sigaux J et al) – Results from the STRASS trial showing that 50% of patients who tapered anti-TNF while in stable remission were able to maintain tapered regimen at 3 years. Maintenance of anti-TNF was high (68% at 3 years) in patients with established RA treated according to the treat-to-target paradigm, with no difference between the 2 initial RCT arms (S-arm, progressive injection spacing and M-arm (full regimen). More than 1/3 of patients received the tapered anti-TNF regimen.
FRI0447 (Kavanaugh A et al) – 3 year treatment data from the PALACE study of apremilast (APR) in patients with active PsA despite previous conventional disease-modifying antirheumatic drug (DMARD) or biologic therapy. 504 randomized patients received ≥1 dose of study medication (PBO: n=168; APR30: n=168; APR20: n=168). In an “as observed” analysis, 53.2% (APR30) and 59.6% (APR20) of patients achieved a modified ACR20 response at Wk 52. In year 2, 65.3% (APR30) and 60.9% (APR20) attained these responses at Wk 104. Patients receiving APR30 at Wk 156 demonstrated sustained improvements, as shown by ACR20 of 65%, swollen/tender joint count mean percent improvements of -81.2% and 73.2%, and HAQ-DI mean change of -0.37, and 41.9% of patients reaching DAS (CRP) <2.6. No new safety concerns were identified with up to 156 wks of APR treatment.
AB0324 (I’Ami MJ et al) – Interim analysis at Week 26 of tapering of Adalimumab based on therapeutic drug monitoring in rheumatoid arthritis. Patients with an adalimumab concentration >8 mL/L were randomly (1:1) assigned to continuation of adalimumab every other week (continuation group) or prolongation of the dosage interval to once every 3 weeks (tapering group), independently of disease activity score in 28 joints (DAS28). At 26 weeks, mean ΔDAS28 did not meet the criteria for a clinically relevant difference in both continuation group (0.29± 0.58 standard deviation (SD)) and tapering group (-0.06±0.58 SD) and did not significantly differ (p=0.06) between groups. This interim analysis shows that disease activity remains stable in RA patients with adalimumab concentrations >8 mL/L who prolonged their dose interval to once in the three weeks compared to patients who continued adalimumab every other week.

These were my highlights from EULAR 2016.




Saturday, 9 April 2016

Spondyloarthritis Special Interest Group (SIG)

The programme for this year's Spondyloarthritis Special Interest Group (SIG) at the British Society for Rheumatology (BSR) Annual General Meeting in Glasgow, 26th April 2016 is now out.

Spondyloarthritis Special Interest Group (SIG) of the British Society of Rheumatology (BSR)

The Spondyloarthritis (SpA) SIG covers issues relating to the group of conditions, including ankylosing spondylitis and psoriatic arthritis. This SIG aims to keep all members up to date with a broad range of topics including early detection, assessment and new therapies.  It also covers research, guidelines and nationally relevant issues such as NICE guidelines and commissioning. The group meet once a year at the BSR and also aims to keep all members updated via email during the rest of the year. The field of SpA is evolving rapidly, and members will find this SIG an invaluable way of keeping up to date.

13 SIG08 - Spondyloarthritis special interest group

April 26, 2016, 11:30 AM - 1:00 PM          

DESCRIPTION

This is the SIG meeting for spondyloarthritis. This is a rapidly expanding field and this SIG aims to be the umbrella group bringing all the work in this area together. It will provide the latest update in pathogenesis and treatments in this field. There will also be an update of intiatives to improve outcomes in spondyloarthritis. This includes updates from partner groups and collaborators. The session will also cover the organisation and delivery of rheumatology services local the venue of the BSR 2016 (Glasgow).

6 Presentations

11:30 - 1:00 PM - Chair
Antoni T. Chan, Department of Rheumatology, Royal Berkshire NHS Foundation Trust, Reading, UNITED KINGDOM.

11:30 - 1:00 PM - Chair
Bruce Kirkham, Department of Rheumatology, Guys and St.Thomas NHS Foundation Trust, London, UNITED KINGDOM.

11:30 - 11:48 AM              - Factors affecting the composition of the gut microbiota

Karen Scott, Rowett Institute of Nutrition and Health, Aberdeen, UNITED KINGDOM.

11:48 - 12:06 PM               - 50 shades of grey in Glasgow

David Marshall, Department of Rheumatology, Inverclyde Royal Hospital, Greenock, UNITED KINGDOM.

12:06 - 12:24 PM               - Update from BRIT-SPA

Helena Marzo-Ortega, Department of Rheumatology, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UNITED KINGDOM.

12:42 - 1:00 PM                 - New therapies in spondyloarthritis


Iain McInnes, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UNITED KINGDOM.

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.