Carpe Diem Haiku Special No. 182 Ese's third "in the darkest hour "

In the darkest hour

The stars don’t cease to twinkle

And morning isn’t far

Lonely darkness

Tries to cover all candles

Hope lies in a match

http://chevrefeuillescarpediem.blogspot.de/2015/11/carpe-diem-special-182-eses-third-in.html

Sarilumab at the ACR 2015 Meeting in San Francisco

There have been a couple of publications on sarilumab at the ACR 2015 Annual Meeting in San Francisco. I guess that the proliferation of studies hints at Sanofi thinks to bring sarilumab to the market. I think, it’s still too soon to apply for FDA approval. But let’s look at some of the studies; I’ll quote all studies under references with a link to the ACR Meeting Abstracts.

Vibeke Strand and colleagues presented: “Impact of Sarilumab on Fatigue, Pain, Morning Stiffness, Productivity, and Health Related Quality of Life (HRQoL) in Patients with Active Rheumatoid Arthritis Who Were Inadequate Responders or Intolerant of Anti-TNF-α Therapy: Results from a Phase 3 Study (RCT)” This Phase 3 RCT [randomized controlled trial] showed statistically significant and clinically meaningful changes from baseline in fatigue, morning stiffness, pain, productivity and participation, rheumatoid arthritis impact scores and health related quality of life at Week 24.

There were several studies that looked at different dosages and combinations like the one presented by Roy Fleischmann et al. (Abstract No. 970 / Sarilumab in combination with CsDMARDs in patients with active RA and inadequate responders or intolerant of Anti–TNF-alpha Therapy), Arthur Kavanaugh et al. ( ABSTRACT No. 2760 / Efficacy and safety of sarilumab plus MTX in patients with RA), Mark C. Genovese et al. (ABSTRACT No. 2770 / Efficacy of sarilumab plus methotrexate in achieving clinical Remission in patients with active, moderate-to-severe RA), Maxime Dougados et al. (ABSTRACT No. 2761 / IL-6R blockade with sarilumab plus methotrexate results in changes in clinical and laboratory parameters associated with chronic inflammation), or another evalution by Vibeke Strand et al. (ABSTRACT No. 2313 / Responder rates and numbers needed to treat).

Paul Emery and colleagues presented: “Safety and Tolerability of Subcutaneous Sarilumab Compared to Intravenous Tocilizumab in Patients with RA”. Conclusion: “Overall, there was no clinically meaningful difference between the treatment groups with regards to clinical adverse events. Laboratory changes noted in the sarilumab groups were within the same range as those noted in the tocilizumab groups. […]”.

Gerd Burmester and colleagues looked at: “Sarilumab Dose Reduction to Manage Laboratory Abnormalities in an Open-Label Extension Study in RA Patients”. Conclusions: “In this study, reducing the dose from 200 mg q2w to 150 mg q2w to manage laboratory abnormalities allowed the majority of patients to continue in the study for a mean duration of >1.5 years. For patients continuing in the study, these laboratory abnormalities improved during the 6 months following dose reduction, and efficacy was maintained.” Two points: 1. necessity to reduce dose at all makes me uneasy, 2. if efficacy is maintained, why use a higher dosage at all? There might be at least a subgroup of patients, in whom a lower dosage could be possible.

Now, we come to Anita Boyapati and colleagues, who presented: “Evaluation of Bone and Joint Proteins for Prognostic Association with Radiographic Progression and Disease Activity in Methotrexate Inadequate Responder Rheumatoid Arthritis Patients in a Sarilumab Phase 3 Study”. Methods: “Serum markers [RANKL, MMP-3 and MMP-cleaved fragments of collagen types 1 and 3 (C1M and C3M)] were measured at baseline and posttreatment in patients receiving Pbo +MTX (n=128) or subcutaneous SAR 200 mg q2w + MTX (n=131).” Conclusion: “Analysis of markers […] showed correlation in MOBILITY patients. These data suggest that multivariate analysis of markers may be necessary to identify increased risk of joint destruction and elevated disease activity in patients with established RA.” And it shows, what isn’ seen – the necessity of results on radiographic progression. But it isn’t a shortcoming of this study.

I’m following the development around sarilumab for a couple of years now. I still hope that the drug comes to the market. But … do we need sarilumab? What could sarilumab give us, which we can’t get from tocilizumab? Will I split up my IL-6 inhibitor patients in two groups? Right now I can’t answer these questions. And still we need data on radiographic progression.

References:

Strand V, Kosinski M, Graham N, Chen CI, Joseph GJ, Bauer D, Lin Y, Pacheco-Tena C, Fleischmann R. Impact of Sarilumab on Fatigue, Pain, Morning Stiffness, Productivity, and Health Related Quality of Life (HRQoL) in Patients with Active Rheumatoid Arthritis Who Were Inadequate Responders or Intolerant of Anti-TNF-α Therapy: Results from a Phase 3 Study (RCT) [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/impact-of-sarilumab-on-fatigue-pain-morning-stiffness-productivity-and-health-related-quality-of-life-hrqol-in-patients-with-active-rheumatoid-arthritis-who-were-inadequate-responders-or-intoler/. Accessed November 17, 2015.

Fleischmann R, Castelar-Pinheiro G, Brzezicki J, Hrycaj P, Lin Y, van Adelsberg J, Graham N, van Hoogstraten H, Bauer D, Burmester G. Efficacy and Safety of Sarilumab in Combination with Csdmards in Patients with Active Rheumatoid Arthritis Who Were Inadequate Responders or Intolerant of Anti–TNF-α Therapy: Results from a Phase 3 Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/efficacy-and-safety-of-sarilumab-in-combination-with-csdmards-in-patients-with-active-rheumatoid-arthritis-who-were-inadequate-responders-or-intolerant-of-antiaetnf-i%c2%b1-therapy-results-f/. Accessed November 17, 2015.

Kavanaugh A, Kivitz AJ, Miranda P, Fiore S, Fay J, Fan C, van Adelsberg J, Huizinga TWJ. Efficacy and Safety of Sarilumab Plus MTX in Subgroups of Patients with Rheumatoid Arthritis in a Phase 3 Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/efficacy-and-safety-of-sarilumab-plus-mtx-in-subgroups-of-patients-with-rheumatoid-arthritis-in-a-phase-3-study/. Accessed November 17, 2015.

Genovese MC, Stanislav M, van Hoogstraten H, Martincova R, Fan C, van Adelsberg J. Efficacy of Sarilumab Plus Methotrexate in Achieving Clinical Remission, Using 4 Different Definitions, in Patients with Active, Moderate-to-Severe Rheumatoid Arthritis in a Phase 3 Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/efficacy-of-sarilumab-plus-methotrexate-in-achieving-clinical-remission-using-4-different-definitions-in-patients-with-active-moderate-to-severe-rheumatoid-arthritis-in-a-phase-3-study/. Accessed November 17, 2015.

Dougados M, Choy EH, Kameda H, van Adelsberg J, Fay J, Fiore S, Fan C, Schett G. IL-6R Blockade with Sarilumab Plus Methotrexate Results in Changes in Clinical and Laboratory Parameters Associated with Chronic Inflammation in Patients with Moderate-to-Severe RA in a Phase 3 Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/il-6r-blockade-with-sarilumab-plus-methotrexate-results-in-changes-in-clinical-and-laboratory-parameters-associated-with-chronic-inflammation-in-patients-with-moderate-to-severe-ra-in-a-phase-3-study/. Accessed November 17, 2015.

Strand V, Rendas-Baum R, Joseph GJ, Chen CI, van Hoogstraten H, Huizinga TWJ, Genovese MC. Responder Rates and Numbers Needed to Treat Based on Clinically Meaningful Improvements in Patient Reported Outcomes (PROs) Including Health-Related Quality of Life (HRQoL) after Sarilumab Treatment during a Phase III Randomized Controlled Trial (RCT) [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/responder-rates-and-numbers-needed-to-treat-based-on-clinically-meaningful-improvements-in-patient-reported-outcomes-pros-including-health-related-quality-of-life-hrqol-after-sarilumab-treatment-d/. Accessed November 17, 2015.

Emery P, Rondon J, Garg A, van Hoogstraten H, Graham N, Liu M, Parrino J, Spindler AJ, Liu N. Safety and Tolerability of Subcutaneous Sarilumab Compared to Intravenous Tocilizumab in Patients with RA [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/safety-and-tolerability-of-subcutaneous-sarilumab-compared-to-intravenous-tocilizumab-in-patients-with-ra/. Accessed November 17, 2015.

Burmester G, Garg A, van Hoogstraten H, Graham N, Boddy A, Parrino J, Genovese MC. Sarilumab Dose Reduction to Manage Laboratory Abnormalities in an Open-Label Extension Study in RA Patients [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/sarilumab-dose-reduction-to-manage-laboratory-abnormalities-in-an-open-label-extension-study-in-ra-patients/. Accessed November 17, 2015.

Boyapati A, Msihid J, Hamilton JD, Gabay C, Graham N, Fiore S. Evaluation of Bone and Joint Proteins for Prognostic Association with Radiographic Progression and Disease Activity in Methotrexate Inadequate Responder Rheumatoid Arthritis Patients in a Sarilumab Phase 3 Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/evaluation-of-bone-and-joint-proteins-for-prognostic-association-with-radiographic-progression-and-disease-activity-in-methotrexate-inadequate-responder-rheumatoid-arthritis-patients-in-a-sarilumab-ph/. Accessed November 17, 2015.

Sarilumab at the EULAR 2014 Meeting in Paris http://rheumatologe.blogspot.de/2014/06/sarilumab-at-eular-2014-meeting-in-paris.html

Secukinumab at the ACR 2015 Meeting in San Francisco

There have been more than 10 publications on secukinumab at the ACR 2015 Annual Meeting in San Francisco. I feel like watching a poker game in the end phase, an all-in-call.

Xenofon Baraliakos and colleagues looked at: “Effect of Interleukin-17A Inhibition on Spinal Radiographic Changes through 2 Years in Patients with Active Ankylosing Spondylitis: Results of a Phase 3 Study with Secukinumab”. Conclusion: “[…]No radiographic progression was observed in ~80% of the pts receiving secukinumab over 104 wks. […]”. Since the tofacitinib debacle concerning EMEA approval, we know how important radiographic data are.

Juergen Braun and colleagues presented: “Secukinumab Significantly Improves Signs and Symptoms of Active Ankylosing Spondylitis: 52-Week Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial with Subcutaneous Loading and Maintenance Dosing”. In conclusions the authors state: “Secukinumab 150 mg s.c. provided sustained improvements over 52 weeks in the signs and symptoms of AS, reducing inflammation, and improving physical function and health-related quality of life. Secukinumab was well tolerated; safety findings were consistent with previous reports.”

The second set of studies is on psoriatic arthritis.

Arthur Kavanaugh and collegues looked at: “Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Psoriatic Arthritis in Anti-TNF-Naive Patients and Those Previously Exposed to Anti-TNF Therapy: 52-Week Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial with Subcutaneous Dosing”. Conclusion: “Secukinumab provided sustained improvements in the signs and symptoms of PsA in both anti‒TNF-naïve and anti‒TNF-IR pts.”.

I’ll skip a few interesting studies, but will list these under references.

Alice B. Gottlieb and colleagues presented: “Secukinumab Reduces the Burden of Nail and Skin Disease in Patients with Psoriasis and Patients with Psoriatic Arthritis: Results from Two Phase 3 Studies”. Conclusion: “Secukinumab improved nail and skin symptoms in pts with psoriasis with significant nail involvement and in pts with concomitant PsA and nail involvement.” I guess, we all expected that it would be this way!

And Alice B. Gottlieb also presented: “Secukinumab Improves Skin Symptoms and Physical Functioning Compared with Ustekinumab in Patients with Moderate to Severe Psoriasis with Concomitant Psoriatic Arthritis: Subanalysis of a Randomized, Double Blind, Parallel-Group, Active Comparator-Controlled Phase 3b Trial”. Conclusion: “Secukinumab was superior to ustekinumab at improving skin symptoms in patients with moderate to severe plaque psoriasis. In the small sub-group of patients with psoriasis and concomitant PsA, secukinumab showed a trend for improving skin symptoms and physical functioning compared with ustekinumab.” I must admit that this surprised me.

Laure Gossec an colleagues looked at: “Relationship Between Improvements in Fatigue and Signs & Symptoms of Active Psoriatic Arthritis: a Sub-Analysis of a Phase 3 Study with Secukinumab”. Conclusion: “Secukinumab improved fatigue in patients with active PsA regardless of prior anti-TNF therapy. A relationship between improvement in fatigue and improvements in the signs and symptoms of PsA was only shown for ACR 20 response and not for other assessments of disease. These results suggest that fatigue in PsA is not strongly related to disease activity but was still improved by secukinumab.” I’ll have to look all over the studies if improvement of fatigue has been addressed elsewhere.

Secukinumab is already available under the name Cosentyx in Germany for the indication of moderate to severe plaque psoriasis. In the U.S. Secukinumab had been approved by the FDA even earlier. Now, we rheumatologists have to wait, until FDA and/or EMEA approve the use in psoriatic arthritis, ankylosing spondylitis, and other inflammatory rheumatic conditions. I’ll be happy to have a new tool, though we still don’t know if a certain consecutive order of biologics and the small molecule should be recommended.

PS. Since yesterday (26.11.2015) Cosentyx has been approved in Germany for the indications of psoriatic arthritis and ankylosing spondylitis. So, the waiting is over.

References.

Baraliakos X, Deodhar AA, Braun J, Baeten D, Dougados M, Sieper J, Emery P, Readie A, Martin R, Mpofu S, Richards H. Effect of Interleukin-17A Inhibition on Spinal Radiographic Changes through 2 Years in Patients with Active Ankylosing Spondylitis: Results of a Phase 3 Study with Secukinumab [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/effect-of-interleukin-17a-inhibition-on-spinal-radiographic-changes-through-2-years-in-patients-with-active-ankylosing-spondylitis-results-of-a-phase-3-study-with-secukinumab/. Accessed November 16, 2015.

Braun J, Deodhar AA, Sieper J, Dougados M, Porter B, Andersson M, Richards H. Secukinumab Significantly Improves Signs and Symptoms of Active Ankylosing Spondylitis: 52-Week Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial with Subcutaneous Loading and Maintenance Dosing [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-significantly-improves-signs-and-symptoms-of-active-ankylosing-spondylitis-52-week-results-from-a-randomized-double-blind-placebo-controlled-phase-3-trial-with-subcutaneous-loading-and/. Accessed November 16, 2015.

Kavanaugh A, McInnes IB, Mease PJ, Hall S, Chinoy H, Kivitz AJ, Patekar M, Wang Z, Mpofu S. Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Psoriatic Arthritis in Anti-TNF-Naive Patients and Those Previously Exposed to Anti-TNF Therapy: 52-Week Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial with Subcutaneous Dosing [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-the-signs-and-symptoms-of-active-psoriatic-arthritis-in-anti-tnf-naive-patients-and-those-previously-exposed-to-anti-tnf-therapy-52-week-results-from-a/. Accessed November 16, 2015.

Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, Landewé RBM, Nash P, Pricop L, Wang Z, Mpofu S. Secukinumab Provides Sustained Improvements in Psoriatic Arthritis: 2-Year Efficacy and Safety Results from a Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-psoriatic-arthritis-2-year-efficacy-and-safety-results-from-a-phase-3-randomized-double-blind-placebo-controlled-trial/. Accessed November 16, 2015.

Gottlieb AB, Reich K, Wang Z, Milutinovic M, Mpofu S. Secukinumab Reduces the Burden of Nail and Skin Disease in Patients with Psoriasis and Patients with Psoriatic Arthritis: Results from Two Phase 3 Studies [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-reduces-the-burden-of-nail-and-skin-disease-in-patients-with-psoriasis-and-patients-with-psoriatic-arthritis-results-from-two-phase-3-studies/. Accessed November 16, 2015.

Gottlieb AB, Thaci D, Blauvelt A, Milutinovic M, Mpofu S. Secukinumab Improves Skin Symptoms and Physical Functioning Compared with Ustekinumab in Patients with Moderate to Severe Psoriasis with Concomitant Psoriatic Arthritis: Subanalysis of a Randomized, Double Blind, Parallel-Group, Active Comparator-Controlled Phase 3b Trial [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-improves-skin-symptoms-and-physical-functioning-compared-with-ustekinumab-in-patients-with-moderate-to-severe-psoriasis-with-concomitant-psoriatic-arthritis-subanalysis-of-a-randomized-d/. Accessed November 16, 2015.

Betts KA, Mittal M, Joshi A, Song J, Bao Y. Relative Efficacy of Adalimumab Versus Secukinumab in Active Psoriatic Arthritis: A Matching-Adjusted Indirect Comparison [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/relative-efficacy-of-adalimumab-versus-secukinumab-in-active-psoriatic-arthritis-a-matching-adjusted-indirect-comparison/. Accessed November 16, 2015.

Gossec L, Kvien TK, Conaghan PG, Østergaard M, Cañete JD, Gaillez C, Mpofu S, Sherif B, Jugl S. Relationship Between Improvements in Fatigue and Signs & Symptoms of Active Psoriatic: Arthritis a Sub-Analysis of a Phase 3 Study with Secukinumab [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/relationship-between-improvements-in-fatigue-and-signs-symptoms-of-active-psoriatic-arthritis-a-sub-analysis-of-a-phase-3-study-with-secukinumab/. Accessed November 16, 2015.

Mease PJ, McInnes IB, Gottlieb AB, Widmer A, Pricop L, Mpofu S. Secukinumab Safety and Tolerability in Patients with Active Psoriatic Arthritis and Psoriasis: Results from a Pooled Safety Analysis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-safety-and-tolerability-in-patients-with-active-psoriatic-arthritis-and-psoriasis-results-from-a-pooled-safety-analysis/. Accessed November 16, 2015.

Deodhar AA, Baeten D, Sieper J, Porter B, Widmer A, Richards H. Safety and Tolerability of Secukinumab in Patients with Active Ankylosing Spondylitis: Pooled Safety Analysis of Two Phase 3, Randomized, Controlled Trials [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/safety-and-tolerability-of-secukinumab-in-patients-with-active-ankylosing-spondylitis-pooled-safety-analysis-of-two-phase-3-randomized-controlled-trials/. Accessed November 16, 2015.

Baeten D, Blanco R, Geusens P, Sieper J, Jui-Cheng T, Martin R, Porter B, Richards H. Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Ankylosing Spondylitis in Anti-TNF-Naïve Patients and Those Previously Exposed to Anti-TNF Therapy: 52-Week Results from Two Randomized, Double-Blind, Placebo-Controlled Phase 3 Trials [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-the-signs-and-symptoms-of-active-ankylosing-spondylitis-in-anti-tnf-naive-patients-and-those-previously-exposed-to-anti-tnf-therapy-52-week-results-from/. Accessed November 16, 2015.

Baeten D, Braun J, Sieper J, Dougados M, Deodhar AA, Baraliakos X, Porter B, Gong Y, Richards H. Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Ankylosing Spondylitis: 2-Year Efficacy and Safety Results from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-the-signs-and-symptoms-of-active-ankylosing-spondylitis-2-year-efficacy-and-safety-results-from-a-phase-3-randomized-double-blind-placebo-controlled/. Accessed November 16, 2015.

Carpe Diem Haiku No. 860 Cosmic Order

The hunter takes up

The mighty eagle to hunt

Beware small yeanling

Forwards and backwards

The hunters and herders move

In seasons’ circle

http://chevrefeuillescarpediem.blogspot.de/2015/11/carpe-diem-860-cosmic-order.html

Hyaluronic Acid Injections at the ACR 2015 Meeting in San Francisco

There have been two publications on hyaluronic acid injections at the ACR 2015 Annual Meeting in San Francisco.

Kevin Ong and colleagues analyzed retrospective data: “Hyaluronic Acid Injections in Knee Osteoarthritis Patients Are Associated with Delay to Knee Arthroplasty”. They concluded: “Our analysis of elderly knee OA patients showed a significantly longer delay to KA [knee arthroplasty] for those who were treated with HA [hyaluronic acid].” The authors presented a retrospective, observational study, which cannot take into account the placebo effect of an injection. It lacks a control group. Or do we have a control group?

Astrid in “Fringe” asked Dr. Walter Bishop: “What’s this?” And Walter answered: “A watermelon as a control group.”

I don’t see the two groups comparable; the second group isn't a control group. The time intervals are differently fixed: one with the treatment and the other one arbitrarily.

There may be other reasons as well: different coping attitudes (one trying to avoid arthropasty and the other wishing an arthroplasty), waiting for therapeutic effect or others.

All in all, I don’t think that this study has a good point to convince us of using hyaluronic acid in delaying the time to knee arthroplasty.

Gurjit S. Kaeley and colleagues also used retrospective data in their study: “Utilization of Viscosupplementation: 2011 – 2013”. The authors wanted to estimate and compare the prevalence and cost of Viscosupplemention utilization as recent “ American Academy of Orthopedic Surgeons (AAOS) guidelines have strongly recommended against use of hyaluronic acid because of lack of clinical improvement compared with placebo.” The authors concluded: “This study highlights the significant cost of VS [viscosupplementation ] in the Medicare population. […] In view of the negative recommendations by the AAOS [American Academy of Orthopedic Surgeons] against the use of Hyaluronic acid joint injections, the current trajectory of use of Hyaluronic acid may not represent optimal value care.”

Hyaluronic acid in knee osteoarthritis hasn’t proven efficacy like clinical improvement compared with placebo or delaying the time to knee arthroplasty. Therefore guidelines recommend against using it.

In Germany hyaluronic acid injections aren’t covered by the compulsory health insurance system, so patients have to pay for injection and medication.

I would not use hyaluronic acid in knee osteoarthritis.

References:

Ong K, Anderson A, Lau E, Niazi F, Fierlinger A, Kurtz S, Altman R. Hyaluronic Acid Injections in Knee Osteoarthritis Patients Are Associated with Delay to Knee Arthroplasty [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/hyaluronic-acid-injections-in-knee-osteoarthritis-patients-are-associated-with-delay-to-knee-arthroplasty/. Accessed November 16, 2015.

Kaeley GS, Thway M, Dodani S. Utilization of Viscosupplementation: 2011 – 2013 [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/utilization-of-viscosupplementation-2011-2013/. Accessed November 16, 2015.

Carpe Diem Haiku Extra No. 40 Shaman Haiku

In the dark storehouse

The shaman keeps drumming on

Then hunters don skis

The hunters on skis

Follow the reindeer through snow

But wind grows heavy

A lake full of fish

But the long boat is struggling

As wind god rages

Back at the cult place

As the spirit of death struck

Shaman starts drumming

It is a story of the magic drum.

http://chevrefeuillescarpediem.blogspot.de/2015/11/carpe-diem-extra-40-shaman-haiku.html 

Smoking and the ACR 2015 Meeting in San Francisco

I cannot discuss all the 25 studies on smoking in detail, which were presented at the ACR 2015 Annual Meeting in San Francisco, but I have selected a few and will summarize the others. Effects on pain are seen with and without concomitant inflammation. So we see worsening in inflammatory rheumatic diseases as well as in fibromyalgia.

Adam Schiffenbauer and colleagues looked at smoking and the development of mysitis antibodies. Conclusion: “These data suggest that in Caucasians smoking is a risk factor for developing ILD, as well as anti-Jo-1 Abs and ASA, but is protective for anti-TIF-1, -Mi-2, and -MJ Abs.”Interestingly they didn’t find this impact in African Americans.

Jasvinder A. Singh and colleagues presented a study on “Perioperative Interventions for Smoking Cessation in Hip and Knee Arthroplasty for Osteoarthritis and Other Non-Traumatic Diseases”. They’ve concluded: “With an overall high grade of evidence, Perioperative smoking cessation therapy is significantly more efficacious than placebo in preventing incidence of complications after knee or hip replacement.”

Karin Magnusson and colleagues’ study: “Smoking and Alcohol Use Are Associated with Structural and Inflammatory Hand Osteoarthritis Features in a Population Based Study”. The authors come to a rather irritating conclusion: “Our results suggest a protective effect of smoking on radiographic hand OA whereas alcohol consumption may increase the risk of joint inflammation in hand OA.”

Axel Finckh1and colleagues  Inform us on: “The Impact of Tobacco Smoking on the Effectiveness of Abatacept in Rheumatoid Arthritis: […]”.Conclusion: “Data from this Pan-European registry analysis suggest that smoking is associated with a decreased effectiveness of ABA, with higher discontinuation rates and lower response rates, as has previously been reported for methotrexate and anti-TNF agents.”

Daniel Wendling and colleagues presented this study: “ASDAS-Based Remission Was Less Frequent Than Basdai-Based Remission, and Both Were Related to CRP and Smoking in Early Axial Spondyloarthritis”. Conclusion: “[…] smoking appears as a major marker of disease activity and remission in early AxSpA.”

Kristina SCHREIBER and colleagues concluded from their study: “Current and past smocking is associated with an increased disease activity (BASDAI and ASDAS-CRP respectively) and functional impairment. Pathogenesis remains to be determined. Smoking cessation should be encouraged in axSpA although these results suggest that it may not impact disease prognosis.”

Jeffrey A. Sparks and colleagues: “Smoking Behavior Changes after Rheumatoid Arthritis Diagnosis and Risk of Mortality during 36 Years of Prospective Follow-up”. They concluded: “Despite the known harmful effects of smoking in chronic diseases, only 16% of smokers quit after diagnosis with RA and maintained smoking cessation during follow-up. Smoking >5 pack-years after RA diagnosis was associated with increased mortality, independent of smoking before RA diagnosis. Interventions promoting cessation of smoking for patients newly diagnosed with RA may diminish the excess mortality of RA.”

Patricia P. Katz and colleagues on: “Impact of Smoking on Patient-Reported Disease Status and Symptoms Among Women with Lupus”. Conclusion: “While current smoking was not common, it was associated with significantly worse patient assessments of lupus status and worse symptoms. […].”

These and other studies underline the importance to actively promote the cessation of smoking in all of patients, who are treated in rheumatology.

References:

Schiffenbauer A, Smith N, Rider LG, Miller FW. Tobacco Smoking in Different Racial Groups Is Differentially Associated with the Development of Myositis Autoantibodies and Interstitial Lung Disease in the Idiopathic Inflammatory Myopathies [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/tobacco-smoking-in-different-racial-groups-is-differentially-associated-with-the-development-of-myositis-autoantibodies-and-interstitial-lung-disease-in-the-idiopathic-inflammatory-myopathies/. Accessed November 15, 2015.

Bharat A, Singh JA. Perioperative Interventions for Smoking Cessation in Hip and Knee Arthroplasty for Osteoarthritis and Other Non-Traumatic Diseases [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/perioperative-interventions-for-smoking-cessation-in-hip-and-knee-arthroplasty-for-osteoarthritis-and-other-non-traumatic-diseases/. Accessed November 15, 2015.

Magnusson K, Mathiessen A, Hammer HB, Natvig B, Hagen KB, Østerås N, Haugen IK. Smoking and Alcohol Use Are Associated with Structural and Inflammatory Hand Osteoarthritis Features in a Population Based Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/smoking-and-alcohol-use-are-associated-with-structural-and-inflammatory-hand-osteoarthritis-features-in-a-population-based-study/. Accessed November 15, 2015.

Finckh A, Gottenberg J, Hernández MV, Iannone F, Lie E, Canhao H, Pavelka K, Turesson C, Lund Hetland M, Mariette X. The Impact of Tobacco Smoking on the Effectiveness of Abatacept in Rheumatoid Arthritis: Data from a Paneuropean Analysis of RA Registries [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/the-impact-of-tobacco-smoking-on-the-effectiveness-of-abatacept-in-rheumatoid-arthritis-data-from-a-paneuropean-analysis-of-ra-registries/. Accessed November 15, 2015.

Wendling D, Guillot X, Gossec L, Prati C, Saraux A, Dougados M. ASDAS-Based Remission Was Less Frequent Than Basdai-Based Remission, and Both Were Related to CRP and Smoking in Early Axial Spondyloarthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/asdas-based-remission-was-less-frequent-than-basdai-based-remission-and-both-were-related-to-crp-and-smoking-in-early-axial-spondyloarthritis/. Accessed November 15, 2015.

SCHREIBER K, Barnetche T, Combe B, Morel J, Daien CI. Current and Past Smoking Are Associated with Functional Impairement and Increased Disease Activity in Axial Spondyloarthritis: Systematic Review and Meta-Analysis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/current-and-past-smoking-are-associated-with-functional-impairement-and-increased-disease-activity-in-axial-spondyloarthritis-systematic-review-and-meta-analysis/. Accessed November 15, 2015.

Sparks JA, Nguyen USDT, Chang SC, Zhang Y, Choi H, Karlson EW. Smoking Behavior Changes after Rheumatoid Arthritis Diagnosis and Risk of Mortality during 36 Years of Prospective Follow-up [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/smoking-behavior-changes-after-rheumatoid-arthritis-diagnosis-and-risk-of-mortality-during-36-years-of-prospective-follow-up/. Accessed November 15, 2015.

Katz PP, Chakravarty E, Katz RS, Michaud K. Impact of Smoking on Patient-Reported Disease Status and Symptoms Among Women with Lupus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/impact-of-smoking-on-patient-reported-disease-status-and-symptoms-among-women-with-lupus/. Accessed November 15, 2015.