The article published by Landewe et al. (1) offers novel insights to
assess the benefits of new therapeutic strategies in rheumatoid arthritis
(RA) which focus more on [the visualization of] structural integrity
rather than the inhibition of radiographic progression (1). The authors
clearly outline the three major problems of the common superiority study
designs: I. Differences in progression are...
The article published by Landewe et al. (1) offers novel insights to
assess the benefits of new therapeutic strategies in rheumatoid arthritis
(RA) which focus more on [the visualization of] structural integrity
rather than the inhibition of radiographic progression (1). The authors
clearly outline the three major problems of the common superiority study
designs: I. Differences in progression are too small, II. Effective
Disease Modifying Antirheumatic Drugs used in the control group results in
levels of radiographic progression which are too low, III. The length of
placebo treatment is limited to 3 months preventing an exploration of
radiological progression of up to 12 months, which often overestimates the
true progression. Furthermore, no alternative for radiographs as a gold
standard imaging technique exists to quantify radiological progression in
Randomized Controlled Trials (RCT). Radiological progression is precisely
assessed by established scoring methods using the quantification of
erosions and joint space narrowing. Magnetic Resonance Imaging (MRI) as an
innovative and sensitive imaging technology has the potential to evaluate
RA related joint damage and structural integrity but only for early stages
of RA: As pointed out by Landewe et al., we also fully agree that MRI is
limited by the differing technical configurations as well as in the
quantification of joint space narrowing, especially for long-term
observations in RCT.
As discussed by Landewe et al. one possible solution could be the
initiation of non-inferiority trials or the use of enriched study
populations to overcome the above mentioned limitations and to achieve the
value of significance. Other solutions to detect smaller changes in
radiological progression and quantification of structural integrity might
include the introduction of computer-assisted techniques for
quantification of erosions (2), metacarpal bone mineral density (3) and
for measurement of joint space width (4). Computer-based quantifications
of metacarpal bone mineral density and joint space narrowing have
demonstrated the ability to detect very small change (5, 6). In a head-to-
head comparison between the Sharp score and computer-assisted joint space
analysis the computer- based technique was able to verify smaller changes
in joint space width independent of the severity of RA (7). Additionally,
the computer based quantification of metacarpal bone mineral density by
digital x-ray radiogrammetry has been able to quantify therapeutic effects
based on the PREMIER study and the BesT study (8, 9). In this context,
computer-assisted joint space analysis was also able to verify therapy
associated changes of joint space width in RA-patients (7).
Quantitative data derived from computer-based techniques seems to support
and validate established scoring methods. Thus optimal individual
therapeutic strategies in daily clinical practice can be designed with
less uncertainty, and the quantification of structural integrity in RCT
poses an additional benefit. The more widespread use of computer-based
methods will help close the gap between visualization of structural damage
and inhibition of radiographic progression. Despite remaining issues of
complexity, quantitative data derived from computer-based techniques
support and validate established scoring methods.
References
1. Landewe R, Strand V, van der Heijde D. From inhibition of
radiographic progression to maintaining structural integrity: a
methodological framework for radiographic progression in rheumatoid
arthritis and psoriatic arthritis clinical trials. Ann Rheum Dis
2013;72(7):1113-7.
2. Langs G, Peloschek P, Bischof H, et al. Model-based erosion
spotting and visualization in rheumatoid arthritis. Acad Radiol
2007;14(10):1179-88.
3. Boettcher J, Pfeil A, Rosholm A, et al. Digital X
-ray radiogrammetry combined with semiautomated analysis of joint space
widths as a new diagnostic approach in rheumatoid arthritis: a cross-
sectional and longitudinal study. Arthritis Rheum 2005;52(12):3850-9.
4. Pfeil A, Haugeberg G, Hansch A, et al. Value of digital X-ray radiogrammetry in the assessment of
inflammatory bone loss in rheumatoid arthritis. Arthritis Care Res
(Hoboken) 2011;63(5):666-74.
5. Hoff M, Haugeberg G, Odegard S, et al. Cortical hand bone loss after 1 year in early
rheumatoid arthritis predicts radiographic hand joint damage at 5-year and
10-year follow-up. Ann Rheum Dis 2009;68(3):324-9.
6. Sharp JT, Angwin J, Boers M, et al. Multiple computer-based methods of measuring joint space width
can discriminate between treatment arms in the COBRA trial -- Update of an
ongoing OMERACT project. J Rheumatol 2009;36(8):1825-8.
7. Pfeil A, Oelzner P, Bornholdt K, et al. Joint damage in rheumatoid arthritis: assessment of a
new scoring method. Arthritis Res Ther 2013;15(1):R27.
8. Hoff M, Kvien TK, Kalvesten J, et al. Adalimumab
therapy reduces hand bone loss in early rheumatoid arthritis: explorative
analyses from the PREMIER study. Ann Rheum Dis 2009;68(7):1171-6.
9. Guler-Yuksel M, Allaart CF, Goekoop-Ruiterman YP, et al. Changes in hand and generalised bone mineral density
in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis
2009;68(3):330-6.
I read with interest the article by Smith et al, which provides encouraging data on safety and potential efficacy of rituximab in a subset of patients with diffuse cutaneous systemic sclerosis (DcSSc). It lends support to the concept that B-cell depletion could be a relatively safe and effective strategy DcSSc. The effects on skin thickening differ from those published by Lafyatis et al, indicating a prospec...
I read with interest the article by Smith et al, which provides encouraging data on safety and potential efficacy of rituximab in a subset of patients with diffuse cutaneous systemic sclerosis (DcSSc). It lends support to the concept that B-cell depletion could be a relatively safe and effective strategy DcSSc. The effects on skin thickening differ from those published by Lafyatis et al, indicating a prospective,controlled,randomised trial is urgently needed.
There is currently no gold standard measure of disease activity in SSc, which would facilitate clinical trials. The authors refer to a disease activity score in Table 1B, it would be helpful if they explain what score they have used (including a reference).
The Leader [1] is an insufficiently objective reaction, and
one that demonstrates rather little real-life insight from the authors.
Insufficiently objective, because it strongly highlights the matter
of the outcome measures, while it only slightly touches on the question:
is the study by Winters et al,[2] one of the two other (Dutch)
randomised studies they use for their substantiation, a valid...
The Leader [1] is an insufficiently objective reaction, and
one that demonstrates rather little real-life insight from the authors.
Insufficiently objective, because it strongly highlights the matter
of the outcome measures, while it only slightly touches on the question:
is the study by Winters et al,[2] one of the two other (Dutch)
randomised studies they use for their substantiation, a valid study? The
answer is: No. As the full text [2] shows, the physiotherapists in the
study were not allowed to use manual mobilization or manipulation. This
is an aberration from the average daily practice in physiotherapy practices.
Not only internationally speaking, but concerning the Netherlands as well.
In the Netherlands, in June 2001 there were 12,600 physiotherapists working
in primary care practices. The Dutch Association for Manual Therapy ("Nederlandse
Vereniging voor Manuele Therapie", NVMT) approached 2000 members then.
Important, then, is to note that that association only represents those
manual therapists that have passed their exam, after having gone
through
their course. There are many more (post-academic)
manual therapy schools in the Netherlands, but they are not recognized
by the NVMT (for some scientifically unproved, and in my opinion largely
invalid reason). I cannot, at this time, get the figures from the other
manual therapy schools, but I'd expect at least half of the Dutch
physiotherapists to be sufficiently trained post-academically to apply
manual techniques in a professional manner. Besides that, physiotherapy
schools themselves since decades teach basic manual techniques. As early
as 1979, when I started, they were already taught.
The question "Does manual therapy offer an additional effect, even in
what is referred to as synovial complaints?" can be answered with yes,
even though the evidence consisted of just one randomised controlled trial:
Bang & Deyle [3] found that additional manual therapy gave a pain decrease
from ~575 to ~175, and physiotherapy without from ~560 to ~360. With
6 treatments.
The Leader is one that shows rather little real-life insight, because
it skips the most important question: How are we doing? We = primary care
in general. How have we come up with a cure for the majority of the patients?
The logical sequence would be: first find a basic cure, even if that would
consist of multiple methods combined, and then seek out what the most economic
method or therapeutical sequence is, for which patient. It is disappointing
that the authors of the Leader ask the question: "Physiotherapy or
corticosteroid injection for shoulder pain?" From what I have been
reading, and in my experience, there is every reason to believe that a
combination of the two, with the inclusion of a wait-and-see period and
NSAIDs, in select patients, would be the most (cost-)effective treatment.
As figure 1 of the Leader shows, the separate methods cannot even cure
20% each. (The results of Winters et al [74% of the injection group
feeling cured at 5 weeks] should be seen in the light of the follow-up
at 11 weeks [table 3 of their text]: at that time only 8.3% of the injection
group felt cured, indicating an extremely high relapse percentage.) Nor
has science come up with a clear and valid answer as to why it would be
impossible to cure more of them. Patients and policy makers reading the
Leader may therefore well think: "What on earth are they doing? Fighting
each other over economic details while the vast majority of us/them is
not cured, nor an acceptable answer is found as to why that would be impossible??"
To maximize the chance of a cure, I would therefore think there is no
reason to divert from a pragmatic one. Consisting, in most non-traumatic
shoulder complaints, roughly of physiotherapy (which should include manual
therapy; if in doubt the general practitioner should contact the therapist)
for scapular pain (a frequently presented shoulder complaint, but
in fact usually referred pain from the cervico-thoracic spine), corticosteroids
and/or anaesthetics and/or distension with saline for serious glenohumeral,
subacromial or acromioclavicular complaints, and again physiotherapy for
the rest. Depending on the course of the complaints, a wait-and-see period
with NSAIDs may be appropriate and should be discussed with the patient
as well, just as that all treatment options should (I'd think that should
be standard practice). For an example of such a pragmatic guideline, further
differentiation, and the substantiation of a number of items mentioned
above, see www.ptlitup.com | Archive
& Search | Shoulder Complaints: Diagnosis & Treatment.
References
(1) Van der Windt DAWM, Bouter LM, Physiotherapy or corticosteroid
injection for shoulder pain? Ann Rheum Dis 2003; 62: 385-387. [Full
text]
(2) Winters JC, Sobel JS, Groenier KH, Arendzen HJ, Meyboom-de
Jong B. Comparison of physiotherapy, manipulation, and corticosteroid injection
for treating shoulder complaints in general practice: randomised, single
blind study. BMJ 1997;314:1320–5. [Abstract/Free
Full Text]
(3) Bang MD, Deyle GD. Comparison of supervised exercise with
and without manual physical therapy for patients with shoulder impingement
syndrome. J Orthop Sports Phys Ther 2000;30:126–37. [Medline]
This is an interesting paper; however I was surprised at the vagueness of the conclusion. The authors showed a significantly increased 'ratio of lymphoma' with adalimumab (4.1) and infliximab (3.6) vs. entanercept
(0.9). Unless some confounding variable is discovered, the conclusion would seem clear. Either adalimumab and infliximab predispose to lymphoma, or entanercept prevents it.
This is an interesting paper; however I was surprised at the vagueness of the conclusion. The authors showed a significantly increased 'ratio of lymphoma' with adalimumab (4.1) and infliximab (3.6) vs. entanercept
(0.9). Unless some confounding variable is discovered, the conclusion would seem clear. Either adalimumab and infliximab predispose to lymphoma, or entanercept prevents it.
The 'conclusion' that the general "two to threefold" increase is "similar to that expected" may suggest the latter explanation is indeed possible, but seems rather to miss the point and suggests on the part of the authors
either a lack of confidence in their own data or a wish not to offend.
We thank dr Barta for his comments on our manuscript ‘anti-
Saccharomyces cerevisiae IgA antibodies are raised in ankylosing
spondylitis and undifferentiated spondyloarthropathy’.[1]
We are fully aware of the importance of gut inflammation in
spondyloarthropathies (SpA).[2] In our view, the finding of ASCA in SpA
provides further evidence for the concept that inflammatory bowel disease
and SpA...
We thank dr Barta for his comments on our manuscript ‘anti-
Saccharomyces cerevisiae IgA antibodies are raised in ankylosing
spondylitis and undifferentiated spondyloarthropathy’.[1]
We are fully aware of the importance of gut inflammation in
spondyloarthropathies (SpA).[2] In our view, the finding of ASCA in SpA
provides further evidence for the concept that inflammatory bowel disease
and SpA are related. However, we were not able to demonstrate an
association between gut inflammation and ASCA levels in our cohort. We are
currently analyzing in a larger cohort of SpA patients the relationship
between ASCA levels and the presence of clinical and histological bowel
inflammation.
We are aware of the fact that ASCA levels are raised in patients with
celiac disease. However, it seems highly unlikely that this would explain
our results. None of the patients in whom ileal biopsies were available
did fulfill histopathologic criteria of celiac disease (increased number
of intra-epithelial lymphocytes, flattening of villi and crypt
hyperplasia). These findings might be expected in ileal biopsies if celiac
disease was present.
As for the suggestion of attempting a yeast-free diet in patients
with Crohn’s disease, to our knowledge, one study has been published using
such an approach.[3] In this study, exclusion of yeast-intake did not
result in a lower Crohn’s disease activity index (CDAI) during the
exclusion period, compared to baseline, although the CDAI was
significantly lower during the exclusion compared to the inclusion period.
Furthermore, such a diet is demanding for the patients and resulted in a
significant weight loss. This limits the practical feasibility of this
possible therapy.
References
(1) Hoffman IE, Demetter P, Peeters M, De Vos M, Mielants H, Veys EM et al.
Anti-Saccharomyces cerevisiae IgA antibodies are raised in ankylosing
spondylitis and undifferentiated spondyloarthropathy. Ann Rheum Dis 2003;62:455-459.
(2) De Keyser F, Elewaut D, De Vos M, De Vlam K, Cuvelier C, Mielants H.
Bowel inflammation and the spondyloarthropathies. Rheum Dis Clin North Am 1998;24(4):785-813.
(3) Barclay GR, McKenzie H, Pennington J, Parratt D, Pennington CR. The
effect of dietary yeast on the activity of stable chronic Crohn’s disease.
Scand J Gastroenterol 1992;27:196-200
In the excellent study recently published in the Annals of the
Rheumatic Diseases [1] F.Moosig et al. evaluated the individualized and
more aggressive strategy of immunosuppressive treatment in 150 patients
with EGPA. Over the last decade we utilized the same approach in our
cohort of 117 patients with EGPA. For induction of remission the authors
used cyclophosphamide in patients not only with Five Fac...
In the excellent study recently published in the Annals of the
Rheumatic Diseases [1] F.Moosig et al. evaluated the individualized and
more aggressive strategy of immunosuppressive treatment in 150 patients
with EGPA. Over the last decade we utilized the same approach in our
cohort of 117 patients with EGPA. For induction of remission the authors
used cyclophosphamide in patients not only with Five Factor Score (FFS) of
0 but with other organ- or life-threatening manifestations, e.g. active
peripheral nervous system involvement, alveolar haemorrhage or severe
eosinophilic alveolitis. FFS was developed in 1996 as a predictor of poor
prognosis in patients with systemic vasculitides [2]. It was revised in
2009 [3]. FFS was used in several trials performed by French Vasculitis
Study Group as a guide to choosing the strategy of initial treatment in
EGPA patients (only corticosteroids if FFS=0 and addition of
cyclophosphamide if FFS?1). In our opinion such simplified approach is
incorrect, at least partly, for the following reasons.
First, FFS is not specific for EGPA as it was developed in the
heterogeneous group of patients with different vasculitides. In fact only
one item of FFS is applicable to EGPA (cardiac disease). Thus, FFS does
not account for common and clinically significant manifestations that
probably cannot predict survival but can impair response to corticosteroid
treatment and lead to disability (e.g. peripheral nervous system
involvement). It should be also noted that cardiac disorders in middle-
aged patients with EGPA may be due to accelerated atherosclerosis.
Second, FFS may be misleading. C.Comarmond et al [4] calculated FFS in the
cohort of 383 patients with EGPA. The estimated original score was 0 in
76.0% of patients while revised FFS had the same value in only 25.6% of
patients. It means that in the latter case three times more patients would
require cyclophosphamide for initial treatment. One of the items included
in the revised FFS is age older that 65. Thus, every elderly patient with
EGPA has FFS of at least 1 and should be treated with cyclophosphamide. Is
age really more important than certain relatively rare but life- or organ-
threatening visceral manifestations, e.g. severe kidney or lung disease?
Systemic necrotizing vasculitides are associated with a high mortality
rate in the elderly. But age itself apparently cannot justify more
aggressive treatment (at least prior to publication of CORTAGE or similar
studies) taking into account higher risk of serious side effects of
corticosteroids and immunosuppressants in the elderly patients.
Third, in the above mentioned French Vasculitis Study Group Cohort the
presence of ANCA was associated with the higher risk of vasculitis
relapses (35.2% versus 22.5% in ANCA-negative patients, P = 0.01) and the
lower risk of death (5.6% versus 12.5%, P < 0.05) [4]. EGPA phenotype
is not an item of FFS though its predictive value deserves evaluation in
the further studies.
Fourth, in C.Ribi et al. study [5] 42% of EGPA patients with FFS = 0
failed to respond to corticosteroid therapy or relapsed during
corticosteroid dosage tapering or after termination of therapy (peripheral
neuropathy and cutaneous lesions were present respectively in 37% and 27%
of these patients). Meanwhile in F.Moosig et al. study the rate of major
relapses in the whole cohort of patients was apparently lower (14%).
We do not challenge the predictive value of FFS but the revised score
should be revised again to be useful as a predictor of response to
immunosuppressive treatment in EGPA patients. Is it really necessary to
calculate any score to choose the best treatment in vasculitis patient? Or
maybe common sense, clinical judgement and clinical experience are better?
Real life is not clinical trial. Scales and scores are important for
evaluation of strategies of treatment but they cannot account for all
challenges that rheumatologist faces in clinical practice.
References
1. Moosig F, Bremer JP, Hellmich B, et al. A vasculitis centre based
management strategy leads to improved outcome in eosinophilic
granulomatosis and polyangiitis (Churg-Strauss, EGPA): monocentric
experiences in 150 patients. Ann Rheum Dis 2013;72:1011-7.
2. Guillevin L, Lhote F, Gayraud M, et al. Prognostic factors in
polyarteritis nodosa and Churg-Strauss syndrome: a prospective study in
342 patients. Medicine (Baltimore) 1996;75:17-28.
3. Guillevin L, Pagnoux C, Seror R, et al. The Five-Factor Score
revisited: assessment of prognoses of systemic necrotizing vasculitides
based on the French Vasculitis Study Group (FVSG) cohort. Medicine
(Baltimore) 2011;90:19-27.
4. Comarmond C, Pagnoux C, Khellaf M, et al. Eosinophilic granulomatosis
with polyangiitis (Churg-Strauss): clinical characteristics and long-term
followup of the 383 patients enrolled in the French Vasculitis Study Group
cohort. Arthritis Rheum 2013;65:270-81.
5. Ribi C, Cohen P, Pagnoux C, et al. Treatment of Churg-Strauss syndrome
without poor-prognosis factors: a multicenter, prospective, randomized,
open-label study of seventy-two patients. Arthritis Rheum 2008;58:586-94.
Dr Peters and co-workers conducted a case-control study, which showed that myocardial infarction (MI) was a 2-3-fold increased in patients with ankylosing spondylitis (AS). They compared AS patients to a sample of the
Dutch general population. We are concerned that the association is (largely) explained by inappropriate selection of controls, instead of reflecting a causal pathway [1]. The authors compared...
Dr Peters and co-workers conducted a case-control study, which showed that myocardial infarction (MI) was a 2-3-fold increased in patients with ankylosing spondylitis (AS). They compared AS patients to a sample of the
Dutch general population. We are concerned that the association is (largely) explained by inappropriate selection of controls, instead of reflecting a causal pathway [1]. The authors compared self-reported myocardial infarction in a well-defined cohort of AS patients, with MI events from LINH, a Dutch general practice database with electronic health care records. Although it is very difficult to estimate incidence rates of myocardial infarction in the Netherlands, we think that the rates in LINH are substantially underestimated. In LINH, overall incidence rates of MI were 1.0-1.1 / 1000 person years between 2002-2008 [2]. In contrast, when linking primary care with hospitalisation and other registries, incidence
rates of MI were 2-3 times higher in the year 2000: 1.7/1000 person years for women, and 3.0/1000 person years for men [3]. The observed association between AS and MI, may be explained by selection bias, as a result of
substantial under-recording of MIs in the LINH database.
References
1. F. de Vries, C. de Vries, C. Cooper et al. Reanalysis of two studies with contrasting results on the association between statin use and fracture risk: the General Practice Research Database. International
Journal of Epidemiology 2006 35(5):1301-1308.
2. http://www.linh.nl/, accessed 13 March 2010.
3. H.L. Koek, A. de Bruin, A. Gast, et al. Incidence of first acute myocardial infarction in the Netherlands. Neth J Med 2007; 65(11):434-441.
Patient No. 2, described by Quintero, et al. in "Antiphospholipid
antibody syndrome associated with primary angiitis of the central nervous
system: report of two biopsy proven cases," [Ann Rheum Dis 2006; 65: 408-
409] had amyloid angiopathy and CNS angiitis. The association between
these two entities has been repeatedly described, most recently and most
carefully by Scolding, et al., in Brain 2005;...
Patient No. 2, described by Quintero, et al. in "Antiphospholipid
antibody syndrome associated with primary angiitis of the central nervous
system: report of two biopsy proven cases," [Ann Rheum Dis 2006; 65: 408-
409] had amyloid angiopathy and CNS angiitis. The association between
these two entities has been repeatedly described, most recently and most
carefully by Scolding, et al., in Brain 2005; 128: 500-515. Patients with
amyloid-associated CNS angiitis may respond to immunosuppressive therapy,
sometimes with resolution of white matter lesions as described in by
Quintero et al.
In this letter we would like to respond to the comments made by Frank
Conijn to our leader.[1]
Firstly, we are aware of the differences in the
content of physiotherapy in the three trials at issue, and briefly
mentioned this in our leader. The fact that passive mobilisations were not
allowed in the trial by Winters et al.[2] may, indeed, partly explain the
differences in effectiveness of...
In this letter we would like to respond to the comments made by Frank
Conijn to our leader.[1]
Firstly, we are aware of the differences in the
content of physiotherapy in the three trials at issue, and briefly
mentioned this in our leader. The fact that passive mobilisations were not
allowed in the trial by Winters et al.[2] may, indeed, partly explain the
differences in effectiveness of physiotherapy across the three trials.
These differences in the content of physiotherapy were already addressed
by Hay et al. [3] in the same issue of the ARD. Therefore, we decided to
focus our leader on the potential influence of heterogeneity in outcome
measures. Clinimetric issues receive little attention in the medical
literature, but may have considerable impact on the outcome of trials, as
was demonstrated in our leader.
We agree with Conijn that it is potentially confusing that the term
physiotherapy may refer to a wide range of interventions. It is perfectly
valid to evaluate the effectiveness of massage, exercises and physical
applications for shoulder pain (as was done by Winters et al.), but it
seems, indeed, inadequate to refer to such an intervention as
"physiotherapy". For many physiotherapists passive mobilisation is an
important component of the treatment of shoulder pain. In future studies
terms should be used that adequately describe the content of treatment,
and not simply refer to the profession of the care providers involved in
the trial.
Secondly, we are familiar with the trial by Bang et al,[4] in which
the added value of passive mobilisations was studied in patients with
shoulder impingement syndrome, and also referred to this trial in our
leader. We strongly believe that the promising results of this study need
further confirmation in larger and different patient groups.
Thirdly, Conijn feels that our leader is one that shows little real-
life insight, because we limited our discussion to the effectiveness of
corticosteroid injection versus physiotherapy. As our leader was written
in connection with the publicaton by Hay et al, we decided to focus our
paper on the research question addressed in this trial. There are, indeed,
many more questions in the treatment of shoulder pain that need to be
resolved. Conijn may be quite right that a stepwise approach (advice,
NSAIDs, physiotherapy, corticosteroid injection) with combined
interventions for those with persistent shoulder problems is the best
strategy for treating shoulder pain in primary care. In fact, most current
guidelines are based on this principle. Further research is needed to
provide evidence for the effectiveness of this management strategy.
Finally, the author seems to have misread Table 3 of the paper by
Winters et al.[2] We were not involved in this trial, but like to correct
this misunderstanding. This table does not present the proportion of
patients cured, but the mean pain scores after 11 weeks of follow-up,
separately for patients who felt cured and for those who did not feel
cured. Conijn highlights the results in the injection group, but pain
scores were very similar in patients treated with physiotherapy (mean
score 8.3 versus 8.2 points). Relapse rates after 11 weeks of follow-up
were also presented in this paper: recurrences were reported by 13% in the
physiotherapy group, and 18% in the injection group (and not by more than
90% as Conijn seems to imply).
We were surprised to be accused of being insufficiently objective in
this opinionated letter, but leave it to others to judge the quality of
our work.
References
(1) Van der Windt DAWM, Bouter LM. Physiotherapy or corticosteroid
injection for shoulder pain. Ann Rheum Dis 2003;62:385-7.
(2) Winters JC, Sobel JS, Groenier KH, Arendzen HJ, Meyboom-de Jong, B.
Comparison of physiotherapy, manipulation, and corticosteroid injection
for treating shoulder complaints in general practice: randomised, single
blind study. BMJ 1997;314:1320-5.
(3) Hay EM, Thomas E, Paterson SM, Dzieczic K, Croft PR. A pragmatic
randomised controlled trial of local corticosteroid injection and
physiotherapy for the treatment of new episodes of unilateral shoulder
pain in primary care. Ann Rheum Dis 2003;62:394-9.
(4) Bang MD, Deyle GD. Comparison of supervised exercise with and without
manual physical therapy for patients with shoulder impingement syndrome. J
Orthop Sports Phys Ther 2000;30:126-37.
I was disappointed in the publication of the concise report on the effects of an orally active Janus kinase (JAK) inhibitor on patient-reported outcomes in rheumatoid arthritis (RA). [1] JAK inhibition represents a new treatment option with potential in RA, so the results of the proof-of-concept trial were of interest, even though it
lasted only 6 weeks; and these were duly published.[...
I was disappointed in the publication of the concise report on the effects of an orally active Janus kinase (JAK) inhibitor on patient-reported outcomes in rheumatoid arthritis (RA). [1] JAK inhibition represents a new treatment option with potential in RA, so the results of the proof-of-concept trial were of interest, even though it
lasted only 6 weeks; and these were duly published.[2] The primary report contained data on American College of Rheumatology (ACR) 20, -50 and -70 response rates, European League Against Rheumatism (EULAR) response rates,
Disease Activity Score in 28 joints (DAS28) results and the change in all individual RA core set measures, as recommended by EULAR/ACR reporting guidelines for clinical trials.[3]
The current consise report duplicates the primary report in the presentation of patient pain, patient assessment of disease activity and physical function (Health Assessment Questionnaire), all components of the RA core set. The only new information is in the results of the Short Form-36 questionnaire. It could be argued that 6-week changes in the scores of this questionnaire carry little import for patients with a lifelong disease such as RA, and that improvements in such questionnaires are unsurprising when disease activity is reduced.
The pharmaceutical industry has a legitimate interest in raising awareness for their innovations. Unfortunately, this is often accompanied by 'slicing and dicing' of study results to increase the number of publications. After a dip caused by the coxib disaster, I note this phenomenon is back with a vengeance.
Clinical researchers serving as investigators on industry-sponsored studies have a responsibility to protect the community against duplicate publication and papers/abstracts that carry little or no new information.
This responsibility also extends to peer reviewers, journal editors and abstract selection committees.
References
1. Coombs JH, Bloom BJ, Breedveld FC, et al. Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial. Ann
Rheum Dis 2010;69:413-6.
2. Kremer JM, Bloom BJ, Breedveld FC, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum 2009;60:1895-905.
3. Aletaha D, Landewe R, Karonitsch T, et al. Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations. Ann Rheum Dis 2008;67:1360-4.
Dear Editor,
The article published by Landewe et al. (1) offers novel insights to assess the benefits of new therapeutic strategies in rheumatoid arthritis (RA) which focus more on [the visualization of] structural integrity rather than the inhibition of radiographic progression (1). The authors clearly outline the three major problems of the common superiority study designs:
I. Differences in progression are...
Dear Editor,
I read with interest the article by Smith et al, which provides encouraging data on safety and potential efficacy of rituximab in a subset of patients with diffuse cutaneous systemic sclerosis (DcSSc). It lends support to the concept that B-cell depletion could be a relatively safe and effective strategy DcSSc. The effects on skin thickening differ from those published by Lafyatis et al, indicating a prospec...
Dear Editor
The Leader [1] is an insufficiently objective reaction, and one that demonstrates rather little real-life insight from the authors.
Insufficiently objective, because it strongly highlights the matter of the outcome measures, while it only slightly touches on the question: is the study by Winters et al,[2] one of the two other (Dutch) randomised studies they use for their substantiation, a valid...
Dear Editor,
This is an interesting paper; however I was surprised at the vagueness of the conclusion. The authors showed a significantly increased 'ratio of lymphoma' with adalimumab (4.1) and infliximab (3.6) vs. entanercept (0.9). Unless some confounding variable is discovered, the conclusion would seem clear. Either adalimumab and infliximab predispose to lymphoma, or entanercept prevents it.
The 'conclusion'...
Dear Editor
We thank dr Barta for his comments on our manuscript ‘anti- Saccharomyces cerevisiae IgA antibodies are raised in ankylosing spondylitis and undifferentiated spondyloarthropathy’.[1]
We are fully aware of the importance of gut inflammation in spondyloarthropathies (SpA).[2] In our view, the finding of ASCA in SpA provides further evidence for the concept that inflammatory bowel disease and SpA...
Dear Editor,
In the excellent study recently published in the Annals of the Rheumatic Diseases [1] F.Moosig et al. evaluated the individualized and more aggressive strategy of immunosuppressive treatment in 150 patients with EGPA. Over the last decade we utilized the same approach in our cohort of 117 patients with EGPA. For induction of remission the authors used cyclophosphamide in patients not only with Five Fac...
Dear Editor,
Dr Peters and co-workers conducted a case-control study, which showed that myocardial infarction (MI) was a 2-3-fold increased in patients with ankylosing spondylitis (AS). They compared AS patients to a sample of the Dutch general population. We are concerned that the association is (largely) explained by inappropriate selection of controls, instead of reflecting a causal pathway [1]. The authors compared...
Dear Editor,
Patient No. 2, described by Quintero, et al. in "Antiphospholipid antibody syndrome associated with primary angiitis of the central nervous system: report of two biopsy proven cases," [Ann Rheum Dis 2006; 65: 408- 409] had amyloid angiopathy and CNS angiitis. The association between these two entities has been repeatedly described, most recently and most carefully by Scolding, et al., in Brain 2005;...
Dear Editor
In this letter we would like to respond to the comments made by Frank Conijn to our leader.[1]
Firstly, we are aware of the differences in the content of physiotherapy in the three trials at issue, and briefly mentioned this in our leader. The fact that passive mobilisations were not allowed in the trial by Winters et al.[2] may, indeed, partly explain the differences in effectiveness of...
Dear Editor,
Dear editor,
I was disappointed in the publication of the concise report on the effects of an orally active Janus kinase (JAK) inhibitor on patient-reported outcomes in rheumatoid arthritis (RA). [1] JAK inhibition represents a new treatment option with potential in RA, so the results of the proof-of-concept trial were of interest, even though it lasted only 6 weeks; and these were duly published.[...
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