Omega-3 fatty acids at the 2017 EULAR Annual Meeting in Madrid

The most interesting feature of omega-3 fatty acids (ω-3 FA) is the conversion into docosahexaenoic acid [DHA], out of which resolvins are derived [1], which are termed specialized proresolving mediators [SPMs]. SPMs possess potent anti-inflammation, tissue protection, and tissue healing activities.

Let’s see what science told us at the 2017 EULAR Annual Meeting in Madrid on omega-3 fatty acids.

H.A. Benabdoune and colleagues presented [2]: “REGULATION OF OSTEOCLAST RECRUITMENT AND ACTIVATION BY RESOLVIN D1”. The study is on murine macrophages and human osteoblasts. The results show, that RvD1 [resolvin D1] strongly reduces osteoclast recruitment and activation. RvD1 decreases bone resorption. The authors concluded: “Our in vitro results clearly show that RvD1 may play an important role in the regulation of bone metabolism. Additionally to our previous data, our findings suggest that RvD1 may offer a novel and original perspective to make a real contribution to musculoskeletal and bone diseases therapy.”

R. Castillo and colleagues looked at [3]: “THE EFFECT OF OMEGA-3 FATTY ACIDS ON DISEASE ACTIVITY, ENDOTHELIAL FUNCTION, INFLAMMATORY MARKERS, AND LIPID PROFILE IN SYSTEMIC LUPUS ERYTHEMATOSUS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED, CONTROLLED TRIALS”. But they had to conclude: “The limited data on the use of omega-3 fatty acids has not shown clear benefit in improving disease activity, endothelial function, inflammatory markers, or lipid profile in patients with SLE [stemic lupus erythematodes]. Larger studies for longer durations using standardized scales for measuring outcomes are needed.”

Am I disappointed? Yes.

In 2013 S.M. Proudman and colleagues published [4]: “Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use”. The authors concluded: “FO [fish oil] was associated with benefits additional to those achieved by combination ‘treat-to-target’ DMARDs [disease modifying anti rheumatic drugs] with similar MTX [methotrexate] use. These included reduced triple DMARD failure and a higher rate of ACR [American College of Rheumatology] remission.”

So, why am I disappointed? Patients ask for guidance in dietary interventions. We as the scientific part of therapy leave this field open to quacks. I think that there is quite a lot of research to be done, which won’t be sponsored by the pharmaceutical industry, yet we need this basic research.

Links and References:

[1] https://en.wikipedia.org/wiki/Resolvin

[2] DOI: 10.1136/annrheumdis-2017-eular.2934

[3] DOI: 10.1136/annrheumdis-2017-eular.2666

[4] http://ard.bmj.com/content/74/1/89

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SB5 or IMRALDI® at the 2017 EULAR Annual Meeting in Madrid

 

As of June 23^rd 2017 Biogen announced, that he Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion for IMRALDI® (also known as SB5, an adalimumab biosimilar). Let’s have a look at this year’s EULAR Annual Meeting. There have been two publications.

J. Kay and colleagues presented [2]: “IMPACT OF ADALIMUMAB SERUM CONCENTRATION ON EFFICACY AND ASSOCIATION BETWEEN ANTI-DRUG ANTIBODIES AND SERUM CONCENTRATION: 24 WEEK RESULTS FROM A PHASE III STUDY COMPARING SB5 (AN ADALIMUMAB BIOSIMILAR) WITH REFERENCE ADALIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS”. Conclusions: “The presence of ADA reduces Ctrough for both SB5 and ADL. In both treatment groups, almost all patients without detectable ADA, but only slightly more than half of patients with ADA, had Ctrough ≥1.274 μg/mL at week 24. Efficacy and ADA incidence were generally comparable between SB5 and ADL regardless of Ctrough level. However, patients with Ctrough ≥1.274 μg/mL generally experienced greater efficacy of both SB5 and ADL than that in patients with Ctrough <1 .274="" add="" ctrough="" data:="" g="" in="" let="" me="" ml.="" patients="" some="" span="" the="" with="">≥1.274 μg/mL groups SB5 patients achieved 32.9 % and ADL patients 43.2 % good EULAR response, SB5 patients achieved 32.9 % and ADL patients 45.2 % low disease activity, and SB5 patients achieved 20.8% and ADL patients 25.9 % remission. Doesn’t look very convincing to me.

J. Ghil and colleagues presented [3]: “USABILITY AND SAFETY OF SB5 (AN ADALIMUMAB BIOSIMILAR) PRE-FILLED SYRINGE AND PRE-FILLED PEN IN PATIENTS WITH RHEUMATOID ARTHRITIS”. Conclusions: “The injection site pain score of PFS and PFP was comparable with overall preference rate higher for PFP. Both PFS and PFP were well tolerated with similar safety profiles.”

I guess, we can agree that these two studies won’t have much impact on EMA’s decision. The decision will be made more on political than medical issues. I’m not a friend of biosimilars, but I know that I’ll have to prescribe Imraldi, if, yes if Abbvie is prudent enough to cut prices for Humira. But why should they act prudently? If you have the number-one prescribed biologic in the world (Humira), you don’t act prudently but haughtily. Pride comes before a fall.

Links and References:

[1] http://media.biogen.com/press-release/biosimilars/biogens-imraldi-adalimumab-biosimilar-candidate-referencing-humira-grantedb

[2] DOI: 10.1136/annrheumdis-2017-eular.3348

[3] DOI: 10.1136/annrheumdis-2017-eular.3350

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Disparities between Objective Measures and Self-report in Fibromyalgia at the 2017 EULAR Annual Meeting in Madrid

There has been a session with four speakers named “Closing the gap between objective measures and self-report in fibromyalgia” at the 2017 EULAR Annual Meeting in Madrid.

M. Henriksen talked on [1]: “DIVERGENCES BETWEEN OBJECTIVE AND SELF-REPORTED PHYSICAL FUNCTION IN FIBROMYALGIA”. “In fibromyalgia (FM), intolerance to physical activity, with increased pain and experience of early muscle fatigue, is a predominant feature.” “Much like central sensitization of pain, it has been suggested that impaired sensory-motor interaction is present in FM, which may be a cause for observed discrepancies between perceived and objective signs of muscle fatigue.” Dr. Henriksen outlined a controlled experiment, in which objective measures were compared to perceived fatigue in fibromyalgia (FM) patients and healthy volunteers after a muscle exhaustion test. FM patients showed central nervous system processes of muscular fatigue “without any evidence of peripheral muscle fatigue”. “The study supports a hypothesis about abnormal sensory-motor interaction among FM patients that can explain the discrepancies between perceived and observed physical disability in FM.”

B. Walitt presented [2]: “COGNITIVE FOG: SUBJECTIVE AND OBJECTIVE

UNDERSTANDINGS OF THE SYMPTOM OF DYSCOGNITION”. Conclusions: “… the experience of cognitive fog is not well captured by current testing paradigms. Subjective complaint is a poor predictor of objective cognitive performance. The neuronal mechanisms responsible for the experience of cognitive fog may be separate from those required to perform cognitive tasks.” Fibro fog is another name for this condition. Sometimes in therapy one can see it that patients unable to read two pages of a book are happy again to read, once the fibro fog is gone.

F. Estevez-Lopez talked on [3]: “ASSOCIATIONS OF PAIN-RELATED COGNITIONS WITH THE DISCORDANCE BETWEEN SUBJECTIVE AND OBJECTIVE PHYSICAL FUNCTION IN FIBROMYALGIA: THE AL-ANDALUS PROJECT”. In the Al-Andalus Project 405 female FM patients and 193 age matched controls were studied with “the Pain Catastrophizing Scale, Chronic Pain Self-efficacy Scale, and physical functioning subscales of the Revised Fibromyalgia Impact Questionnaire (FIQR) and Short Form-36 (SF-36) health survey”. Conclusions: “Although both are markedly impaired, subjective physical function is more impaired than objective physical function in fibromyalgia. Catastrophizing is associated with this discordance.” Allow me to match this with own observations. FM patients were always surprised looking at the Borg scale (rating of perceived exertion) before and after physical training.

L. Piggott looked from the patient’s perspective [4]: “THE DRUGS DON’T WORK”. She talked about “her own search for answers and cure to Fibromyalgia in an attempt to salvage her life and independence, prior to accepting that this is a long-term condition which will require self-management and perseverance.” Mrs. Piggott made the observation that “drugs don’t work”. I can understand the frustration of any FM patient, when drugs don’t work. I’ve written quite often on fibromyalgia and that I don’t think drugs would be the solution [5]. Often drugs create new problems. Analgesics have a place in acute pain (nociceptive pain), but aren’t of much use in chronic pain (non-nociceptive / central pain). F. Wolfe has shown how little effective modern antidepressants are [6]: “Physicians and patients should be realistic about the potential benefits of antidepressants in FMS. A small number of patients experience a substantial symptom relief with no or minor adverse effects. However, a remarkable number of patients dropout of therapy because of intolerable adverse effects or experience only a small relief of symptoms, which does not outweigh the adverse effects.”

There are disparities between objective measures and self-report in fibromyalgia, but in recognizing these, we can gain a new perspective, which enables us as health care professionals to help our patients instead of adding harm.

Links and References:

[1] DOI: 10.1136/annrheumdis-2017-eular.7148

[2] DOI: 10.1136/annrheumdis-2017-eular.7215

[3] DOI: 10.1136/annrheumdis-2017-eular.7185

[4] DOI: 10.1136/annrheumdis-2017-eular.7191

[5] http://rheumatologe.blogspot.de/search?q=Fibromyalgia

[6] https://www.ncbi.nlm.nih.gov/pubmed/22452526

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Abatacept switching from IV to SC and back at the 2017 EULAR Annual Meeting in Madrid

I had already looked at abatacept at the 2017 EULAR Annual Meeting in Madrid [1,2]. Now I have found another issue concerning abatacept. It is about r the ACTION (AbataCepTIn rOutiNe clinical practice) study, which is an observational study, which our employer doesn’t allow us to participate. Let’s have a closer look at the study.

R. Alten and colleagues presented [3]: „ LESS THAN 5% OF REAL-LIFE PATIENTS WHO SWITCH FROM IV TO SC ABATACEPT IN REAL-WORLD CLINICAL PRACTICE SUBSEQUENTLY SWITCH BACK TO THE IV FORMULATION”. Conclusions: “Less than 5% of pts who switched formulation from IV to SC abatacept in real-world clinical practice re-switched to the IV formulation, suggesting that switching has no adverse clinical impact. A change in formulation was mainly due to pt wish, reflecting their involvement in decision-making.”

That is strange indeed. The data reflects real world and not study reality. But I have made the opposite observation. When SC formulation became available, we switched patients from IV to SC and only a few stayed on SC – the very few ones with problematic veins, who suffered multiple IV punctures each time. Another observation at our center: patients, who started SC hardly ever switched to IV. There’s quite a lot of room for interpretation. Maybe patients in an observational study still reflect more a study cohort than real world patients.

Links and References:

[1] http://rheumatologe.blogspot.de/2017/06/blog-eular-2017-abatacept-biosimilars.html

[2] http://rheumatologe.blogspot.de/2017/06/risk-of-opportunistic-infections-in.html

[3] DOI: 10.1136/annrheumdis-2017-eular.1379

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