a big question, but we're getting closer to an answer. People with rheumatoid
arthritis often complain about the influence of weather an disease activity.
There were two studies at the ACR 2013 Meeting in San Diego addressing the
T. Sawada and colleagues presented
the following study [Abstract #1356]: "Disease
Activity Of Rheumatoid Arthritis Is Influenced By Seasonal Change, As Analyzed
Based On a Nationwide Japanese Cohort Database." This study looked more at
seasonal variations than weather and found, that "RA disease activity, as
assessed both subjectively and objectively, was lowest in fall." Sorry,
that won't get us any further, though one would have to take this account, when
doing studies in Japan.
E. Savage and colleagues presented
the second study [Abstract #1359]: "Does
Rheumatoid Arthritis Disease Activity Correlate With Weather Conditions?"
The authors come mostly from Belfast, Northern Ireland, but one also from St.
Vincent’s Hospital, Melbourne, Australia, where I had the pleasure to do some
research on DRGs. I guess that the data has been collected in Belfast. 133
patients either on stable etanercept or adalimumab were recruited for this
study. The authors lokked at "three weather components from the seven
quantitative variables (maximum temperature, minimum temperature, hours of
sunshine, mm rainfall, relative humidity, wind-speed and pressure)."
Conclusion:"This study demonstrates statistically significant
lower DAS-28 scores in sunny and dry conditions. A non-significant trend to
higher DAS-28 scores in times of low temperature, and dull, wet and windy
weather was also noted." I'm surprised to hear about sunny and dry weather
in Belfast, but now we have statistically significant results that prove
It is not uncommon that patients with
rheumatic diseases report an increase of symptoms under certain weather
conditions. Some of my patients feel that it will rain soon based on their symptoms.
Other patients with rheumatoid arthritis report that cold, wet weather
conditions or changes in air pressure will worsen their symptoms, such as pain,
stiffness or joint swelling.
The results of studies on the effects
of weather on the rheumatoid arthritis haven’t been conclusive, but there’s a
new study that proved a link between weather and symptoms, which has been
presented at the ACR 2013 Meeting in San Diego. See link below.
Weather sensitivity - findings from the
last few weeks:
"Not the weather itself, but the
change no matter which direction leads to more complaints." (female, RA)
"If there’s a change in weather. But
I don't know if it isn’t in the mind. If a rain front comes. When the sun
shines, I feel better." (female., RA)
Weather sensitivity: no (female, PsA)
"Maybe it was because poor weather.
I thought the heat was really agreeable. You can’t always blame the weather. If
it wouldn’t come so suddenly, but if the temperatures would go down gradually, so
peu à peu." (female, RA)
"The cold and wet weather is not
conducive. But it's then not particularly severe. The warm weather is good to me,
I don’t get not much flares." (female, AS)
"Really bad. Such a weather [wet,
cold] is fatal." (female, AS)
"Sweating in hot weather, nothing
else." (female, RA)
"Since the weather swings back from
warm to cold, I have more complaints again. But maybe I just feel it in my
head.” (male; RA)
Weather sensitivity: "I'd say
no." (male; RA)
"It depends on the weather. If it’s
wet and cold, I've got more complaints again. I notice 100%, if the weather
turns." (female, RA)
"I immediately notice the change
in the weather in my back." (male; PsA)
"There is a comfortable
temperature. It should be not too hot and not too cold." (female, RA)
"The hands are swollen since the
change in the weather. More fatigue. More sluggish. As usual, when the weather swings."
"With the change in the weather
last week I put on a splint, because the whole right hand hurts very badly. I’ve
put the hand immediately at rest. Then again, the next day, it's alright. I can
tell you, if it's hot, because then my right little finger points to the
outside of my hand." (female, RA)
"When it rains, or when the
weather changes, the pain gets stronger." (male; AS)
"With the rain, it's worse. I have
more pain if it’s damp. (female, RA/SLE)
"I had the feeling for the first
time that it is related to the weather. I've never experienced t this way. The rain." (female, RA)
"It has to be the humidity. Saturday
was my date for the injection, I noticed it two or three days before." (female,
"I'm always weather sensitive. More
problems with damp and cold weather. Even in air-conditioned rooms. Running is
more difficult and breathing, and my heart is racing." (female, RA plus
"Since Thursday I have more
complaints on the back. The rain, the cold." (female; RA)
"Complaints from time to time. Once
the moisture hangs out in the air." (female; AS)
"In the rain all joints hurt. In
wet weather, I notice it immediately, then I can not run. In the summer, it is
better. Now it hurts everywhere." (female; RA)
"Especially now with the weather [it’s
worse again]. Before the weather change arrives. The other day we have rain. Then
I can not sleep." (male; PsoA)
"When the weather change comes, if
it gets wet, when the extreme weather change comes, then stiffness lasts much
longer; then, you don’t want to put the elbow onto somewhere. No matter whether
it turns from good to bad or vice versa." (male; RA)
"Last change in the weather a
fortnight ago led to a swelling under my right foot, lasted 2 and 2½ days. Cooling
with ice also didn’t help. Right hand starting from the outer edge, until it covered
the entire hand." (male; RA)
"When it gets so cold, I've always
cold hands; feet also." (female; RA)
Usually we are talking about T and
B cells in rheumatoid arthritis or maybe dendritic cells, but now neutrophils
and macrophages come into focus. GM-CSF controls
activation, differentiation, and survival of macrophages and neutrophils.
been to an ACR review/update course here in Germany and the colleagues were
very much in favour of this new drug.
been three studies on mavrilimumab at the ACR 2013 Meeting in San Diego.
G.-R. Burmester and colleagues presented the following study [Abstract
#1733]: "Early and Sustained Improvement In Pain and Physical Function As
Measured By Visual Analog Scale and Short Form-36 Physical Component Summary
Score In Rheumatoid Arthritis Patients Treated With Mavrilimumab, An
Investigational Anti-GM-CSFR-Alpha Monoclonal Antibody, In a Phase 2a
Study." Conclusion: "Treatment with mavrilimumab 100mg resulted in an
early onset and sustained improvement in pain relief and physical functioning
as measured by VAS and SF-36 PCS, respectively, in moderate-severe RA patients.
These findings are consistent with improvement in the disease activity
(DAS28-CRP) and support further investigation of the blockade of the GM-CSF
receptor with mavrilimumab in Phase 2b studies conducted in both DMARD-IR and
W. White and colleagues presented
the second study [Abstract #2377]: "Biomarkers
Associated With Rheumatoid Arthritis Disease Activity Including Joint Damage
Correlate With Changes In Clinical Response In Subjects Treated With
Mavrilimumab At Doses Above 10 Mg." Conclusion:"Promising
clinical safety and efficacy results of mavrilimumab support further clinical
development at doses greater than 10 mg. Mechanistically, the drug suppressed
both acute phase and inflammatory blood markers. Tracking of disease activity
by MBDA showed a clear biomarker-based dose-response relationship. The
association of MBSD decline with radiographic damage will be assessed in an
on-going phase 2b study."
But there hasn't been any data on radiographic changes up to now.
P.C. Ryan and colleagues resented a
study on monkeys [Abstract #2378]: "Safety Of
Mavrilimumab In Cynomolgus Monkeys: Relevance Of Nonclinical Findings In Lung
To Human Safety." Conclusion:"These results suggest that
suppressing macrophage activity by targeting GM-CSF receptor alpha may be a
novel approach with an acceptable safety profile for the treatment of RA."
Interestingly in "results" the results of a study published at
the EULAR 2012 Meeting in Berlin has been quoted: "In EARTH,
mavrilimumab demonstrated good clinical activity with
no clinically significant or persistent changes in the lung function tests
performed. Likewise, the serum biomarkers of lung damage, SP-D and KL-6, showed
no clinically significant changes following mavrilimumab treatment." The
study at the EULAR 2012 had been by S. Spitz and colleagues
[Abstract AB0576]; "Evaluation Of Surfactant Protein-D And Kl-6 As
Potential Pulmonary Safety Biomarkers During Mavrilimumab Treatment".
It is like in a detective story - the inspector frowns
if someone gives an alibi without being asked for it. Though as macrophages are
involved the side effects on the lung should be monitored.
The recent data looks much better than what has been
presented last year, but still we lack a study of longer duration with data on
radiographic progression. And as the studies EARTH explorer 1 and 2 look at
other dosages (also 150 mg) and test against golimumab for 24 weeks, results on
radiographic progression still have a long way to come.
Summing it up: it looks better for mavrilimumab than a year ago, but
still we don't know if there's going to be a new drug.