Fibromyalgia at the EULAR 2020 Meeting Online

I have selected a few studies, which were presented at the 2EULAR 2020 Meeting, which has been online because of Covid-19.

The first study has been by B. Kundakci and colleagues [1]: „THU0461 THE COMPARATIVE EFFICACY OF NON-PHARMACOLOGICAL INTERVENTIONS FOR FIBROMYALGIA: A SYSTEMATIC REVIEW WITH BAYESIAN NETWORK META-ANALYSIS“.The authors looked at 78 studies (n = 5,639 participants). Multidisciplinary treatment was the best for improving pain, sleep and depression, balneotherapy and exercise were the most effective treatments for FIQ and fatigue. Allow me to intervene, as one doesn't treat the Fibromyalgia Impact Questionnair, but nevertheless one can see improvement in the score of this questionnaire. 47 exercise trials (n = 3,271 participants) were also analysed. Strengthening showed the greatest benefits for FIQ, pain and depression, whereas aerobic exercise was the best for fatigue and sleep. As the effect size tvaries between interventions and outcomes, the authors conclude, that „the results of this study may be used to guide the selection of the most effective non-pharmacological interventions according to the predominant symptom in individual patients.“ Though the approach with comparing effect sizes is a good idea, I doubt that this will happen in real life.

My next selection is the study by L. López-Núñez and colleagues [2]: „THU0462 CHARACTERIZATION OF PATIENTS WITH FIBROMYALGIA AFFECTS WITH OR WITHOUT JOINT HYPERLAXITY SYNDROME“. If you have read more on my blog you know about my long lasting interests in hyperlaxity or the benign hypermobility syndrome. In their conclusion the authors point out: „Our work revealed that FM patients with JHS are different from FM without JHS, by manifesting differences in certain clinical, anthropometric, and bone metabolism features.“ The Body Mass Index and Muscle Mass were less in the FM-JHS group. The FM-JHS group also had less bone mineral density (BMD) at total hip DXA, which might be due to the lesser weight. So the study gives interesting data, but implications on treatment are not emminent.

The next study is by S. A. A. Tabra and colleagues [3]: „THU0471 VITAMIN D SUPPLEMENTATION; IS IT EFFECTIVE IN FIBROMYALGIA PATIENTS?“ 100 adult patients of primary FMS (according to the 2010 ACR criteria for FMS) associated with vitamin D insufficiency (21-29 ng/mL) took part in this interventional double-blinded study. 21-29 ng/ml is just below normal and after six months the vitamin D group had a level of just above the lower limit (36.8 +/- 3.9 ng/ml). May this be as it is, there have been differences in the results between the vitamin D group and the placebo group. Gth authors concluded, that „Vitamin D supplement is effective as an adjuvant therapy in improving functional status, quality of life and psychological status in fibromyalgia patients with vitamin D insufficiency.“ Please repeat the study with a higher level of vitamin D as a goal.

A. Negm and J. Alsaleh presented [4]: „THU0484 FIBROMYALGIA AND MULTIPLE SWITCHING OF BIOLOGICS IN SPONDYLOARTHRITIS“. The authors looked at 305 patients; but there were only 43 patients with coexisting fibromyalgia. They concluded: „FM coexistence with SpA might impact clinical evaluation of disease activity and possibly negatively affect self-measurement of treatment response. In our study, SPA patients exposed to more biologics if they have coexisting FM; Moreover, they are more frequent switchers among biologics including TNFi and IL17i.“ The study shows that our tools to make treatment decisions in spondyloarthopathies are too inaccurate if it comes to concomitant fibromyalgia.

A. Gomez-Centeno and colleagues presented the folloeing study [5]: „AB0952 COENZYME Q10, TRYPTOPHAN AND MAGNESIUM: A NUTRITIONAL SUPPLEMENT IN THE TREATMENT OF FIBROMYALGIA SYMPTOMS“. I don't know if I should already start to whince. The authors studied 23 patients, whereof 3 dropped out. They found an improvement, but: „no statistically significant differences were found among the studied variables.“ If the statistics do not support your hypothesis, it is premature to draw conclusions. Conduct a study of a larger number of patients and do so for at least half a year. My educated guess is that you won't find statically significant differences.

A. Keskin and colleagues asked [6]: „AB0954 IS CONNECTIVE TISSUE MASSAGE EFFECTIVE IN INDIVIDUALS WITH FIBROMYALGIA?“ They concluded: „According to our results, connective tissue massage has been shown to be effective in reducing the number of painful areas in addition to the positive effects of clinical pilates exercises in individuals with FM. In order to increase the effectiveness of treatment in individuals with FM, we recommend the use of connective tissue massage as an additional treatment method.“ The authors compared an interventional group of N=15 to a control group of N=17. And they found no statistically significant differences in the Fibromyalgia Impact Questionnare (FIQ), the Health Assessment Questionnare (HAQ), the Beck Anxiety Inventory (BAI), the Short Form-36 (SF-36) and the Cognitive Exercise Therapy Approach (BETY) Scale; there has been a difference in the Pain Location Inventory (p=0.023). This is cherry picking and not science. The authors should have formulated a hypothesis and an endpoint.

A. Moshrif and colleagues presented a study on vertical nail ridging [7]: „AB0956 VERTICAL NAIL RIDGING IN PATIENTS WITH FIBROMYALGIA: FREQUENCY, PROPOSED GRADING AND CORRELATION WITH OTHER DISEASE FEATURES.“ The authors concluded: „vertical nail ridging is a frequent finding and can be considered helpful for diagnosis of patients with FM.“ The authors found 98.6% vertical nail ridging in the fibromyalgia group, and they found vertical nail ridging in 76.2% of the control group. If vertical nail ridging is related to stressful conditions, why not look there in the first place? Of what use is a test, if the control group shows the same sign in a high proportion of patients? Maybe the next study shows a correlation between number of freckles in red haired fibromyalgia patients and the development of the FIQ score in the next six months. And please look for a study on vertical nail ridging on PubMed; there is none. The reference in the study [8] is a talk, which has been held in 2007, concerning vertical nail ridging it says: „Another stress-related nail habit that Dr. Mayoral discussed is people who rub their fingers over their thumb nail, which can create a ridge across the nail. This rubbing causes a distortion of the nail plate, and when the nail grows, a raised ridge forms in the middle of the nail.“ I guess looking for vertical nail ridging won't make it into the ACR Fibromyalgia Criteria.

M. Giovale and colleagues presented the following study [9]: „LOW-ENERGY PULSED ELECTROMAGNETIC FIELD THERAPY REDUCES PAIN IN FIBROMYALGIA: A RANDOMIZED SINGLE-BLIND CONTROLLED PILOT STUDY.“ 21 women with fibromyalgia were evaluated in TWO groups, one receiving active treatment under single-blinded condition. Makes me whince again. „In all endpoints, we observed a general reduction at T4 and T8 compared to T0 also for FIQ, VAS pain, SS, SF-36, regardless of the treatment arm and the decrease was higher in the active treatment arm compared to the placebo group, albeit not reaching statistical significance.“ I haven't found the definition of an endpoint. The authors concluded: „The results of our pilot study show that PEMF is more effective than placebo in reducing widespread pain in fibromyalgia while confirming that a placebo effect is clear in this complex disease.“ No, that is what the sponsor of the study likes to hear. The study showed no statistically significant difference between the two groups.

Hoping for better studies in future meetings concernig fibromyalgia.

References:

[1] Kundakci B, Kaur J, Shim SR, et al: THU0461 THE COMPARATIVE EFFICACY OF NON-PHARMACOLOGICAL INTERVENTIONS FOR FIBROMYALGIA: A SYSTEMATIC REVIEW WITH BAYESIAN NETWORK META-ANALYSIS. Annals of the Rheumatic Diseases 2020;79:463-464. http://dx.doi.org/10.1136/annrheumdis-2020-eular.803

[2] López-Núñez L, Blanch J, Ciria Recasens M, et al: THU0462 CHARACTERIZATION OF PATIENTS WITH FIBROMYALGIA AFFECTS WITH OR WITHOUT JOINT HYPERLAXITY SYNDROME. Annals of the Rheumatic Diseases 2020;79:464. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4115

[3] Tabra SAA, Abu-Zaid MH, Hablas S: THU0471 VITAMIN D SUPPLEMENTATION; IS IT EFFECTIVE IN FIBROMYALGIA PATIENTS? Annals of the Rheumatic Diseases 2020;79:468-469. http://dx.doi.org/10.1136/annrheumdis-2020-eular.487

[4] Negm A, Alsaleh J: THU0484 FIBROMYALGIA AND MULTIPLE SWITCHING OF BIOLOGICS IN SPONDYLOARTHRITIS. Annals of the Rheumatic Diseases 2020;79:475-476. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6224

[5] Gomez-Centeno A, Ramentol M, Gonzalez MJ, et al: AB0952 COENZYME Q10, TRYPTOPHAN AND MAGNESIUM: A NUTRITIONAL SUPPLEMENT IN THE TREATMENT OF FIBROMYALGIA SYMPTOMS. Annals of the Rheumatic Diseases 2020;79:1769-1770. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5531

[6] Keskin A, Basakci Calik B, Gur Kabul E, et al: AB0954 IS CONNECTIVE TISSUE MASSAGE EFFECTIVE IN INDIVIDUALS WITH FIBROMYALGIA? Annals of the Rheumatic Diseases 2020;79:1770-1771. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6316

[7] Moshrif A, Abdelkareem M, Moneer M, et al: AB0956 VERTICAL NAIL RIDGING IN PATIENTS WITH FIBROMYALGIA: FREQUENCY, PROPOSED GRADING AND CORRELATION WITH OTHER DISEASE FEATURES. Annals of the Rheumatic Diseases 2020;79:1771. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5317

[8] American Academy of Dermatology. (2007, November 12). Feeling Stressed? How Your Skin, Hair And Nails Can Show It. Science Daily. Retrieved December 30, 2019 from www.sciencedaily.com/releases/2007/11/071109194053.htm

[9] Giovale M, Novelli L, Rampoldi S, et al: AB0958 LOW-ENERGY PULSED ELECTROMAGNETIC FIELD THERAPY REDUCES PAIN IN FIBROMYALGIA: A RANDOMIZED SINGLE-BLIND CONTROLLED PILOT STUDY. Annals of the Rheumatic Diseases 2020;79:1772. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6409

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Fibromyalgia in patients with rheumatoid arthritis and PROs (patient related outcomes)

I’ve just written on the 12^th TNF-alpha-Forum in Munich. Prof. Schulze-Koops talked about patient related outcomes. The gist is: PROs are indispensable tools to capture the functional experience of the patient. PROs capture parameters that are not directly related to inflammation. The scores recorded in disease activity scores with visual analogue scales are not suitable for sensitively and adequately providing information about functionality limitations. PROs are not sufficient to escalate immune-suppressive therapy.

SA Provan and colleagues just published: “Fibromyalgia in patients with rheumatoid arthritis. A 10-year follow-up study, results from the Oslo Rheumatoid Arthritis Register.” The authors concluded: “RA-FM was associated with significantly higher levels of cross-sectional and longitudinal RA disease activity. FM should be considered in patients with RA not reaching remission.”

On the same TNF-alpha-Forum the CAPEA study has been quoted, which shows a constant DAS28 above 3.2 in a little less than 40% of RA patients. After six months nothing changes for the next 18 months.

It means that we have to find tools besides the current disease activity scores to monitor activity, which means to separate pain, inflammation, immunologic parameters, disability and more to come to safer conclusions concerning the escalation or de-escalation of immune-suppressive therapies. The fibromyalgia group could easily receive a more intensive immune-suppression, which would result in a higher risk for infections for instance. By the way, obese women share also this risk as they have elevated inflammation markers.

Links:

http://rheumatologe.blogspot.com/2019/01/12-tnf-alpha-forum-in-munchen_14.html

https://www.ncbi.nlm.nih.gov/pubmed/30620293

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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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Fibromyalgia at the 2017 EULAR Annual Meeting in Madrid - a disease of the peripheral or central nervous system

Fibromyalgia: a disease of the peripheral or central nervous system – that is indeed a provocative question. Or not at all!

C. Sommer talked on [1]: “PERIPHERAL PATHOLOGY IN FIBROMYALGIA”. “In recent years, an involvement of the thinly myelinated nerve fibers of the A-delta type and the unmyelinated C-fibers has been reported in fibromyalgia patients.” And: “While the reasons for this small fiber pathology and its contribution to FMS pain are still unclear, a new research field has emerged that will focus on uncovering the underlying pathophysiology.” So what?! The findings are undisputed, though we still lack data on larger cohorts. I see in focusing on a peripheral pathology a clinging to a straw for drug interventions that have been not so successful.

E. Kosek’s talk has been on [2]: “CENTRAL PATHOLOGIES IN FIBROMYALGIA”. She stated: “Although mechanisms such as muscle ischemia and peripheral nerve fibre pathology have been implicated in fibromyalgia, currently no known peripheral pathology can fully account for the pain. Therefore, the pain in fibromyalgia is most likely explained by a complex interaction between peripheral and central mechanisms.” There are known functional and structural abnormalities in the brains of fibromyalgia patients (MRI). Fibromyalgia patients showed an inability to activate the descending pain inhibitory system. E. Kosek talked on elevated IL-8 in the cerebrospinal fluid and translocator protein (TSPO) in glia cells indicating neuro-inflammation, possibly due to glia cell activation. A positive response to a 12 weeks treatment with a serotonin-noradrenalin re-uptake inhibitor (SNRI) has been seen only in patients with a short duration of fibromyalgia. She referred to the Jensen et al. Study [3]: “In contrast, cognitive behaviour therapy did not affect clinical pain or pain sensitivity but increased activations of cerebral regions implicated in executive cognitive control during painful stimulation and thus likely reappraisal of painful stimuli.” Kosek also looked at physical exercise and ended: “The results demonstrated that different treatment modalities affected specific brain mechanisms, indicating that at least some of the cerebral abnormalities in FM are reversible.”

To sum it up: Fibromyalgia has a complex pathology, which is only understood in parts. Peripheral and central mechanisms interact in the development of fibromyalgia. Before acute pain mutates into chronic pain analgesics should be used; the importance of analgesics dwindles quickly. Serotonin-noradrenalin re-uptake inhibitors play a role in early fibromyalgia; I don’t think that fibromyalgia patients are generally referred to rheumatologists in this stage of the disease. Cognitive behavior therapy in combination with physical exercise are most likely to alleviate fibromyalgia symptoms.

Links and references:

[1] DOI: 10.1136/annrheumdis-2017-eular.7088

[2] DOI: 10.1136/annrheumdis-2017-eular.7142

[3] Jensen et al. Pain 2012:153(7):1495–503

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