RA Drug Fails to Curb Psoriatic Arthritis

By*Nancy Walsh, Staff Writer, MedPage Today
Published: July 25, 2012

Reviewed*by*Zalman S. Agus, MD; Emeritus Professor, Perelman School
of Medicine at the University of Pennsylvania and Dorothy Caputo, MA,
BSN, RN, Nurse Planner
Action Points

Oral methotrexate is likely the most commonly used drug for psoriatic
arthritis and is recommended in most recent guidelines despite a paucity
of randomized trials.

Note that this randomized trial found no evidence of benefit in the
treatment of synovitis in psoriatic arthritis.

Treatment with methotrexate, the cornerstone disease-modifying therapy
in rheumatoid arthritis, had no benefit on synovitis in patients with
psoriatic arthritis, a placebo-controlled trial found.

After adjustment for age, sex, and duration of disease, 6 months of
methotrexate treatment had no statistically significant benefit as
measured on the psoriatic arthritis response criteria (OR 1.77, 95% CI
0.97 to 3.23), according to Gabrielle H. Kingsley, MD, of King's College
London, and colleagues.

However, the treatment did show benefits on patient global assessment
(coefficient ?9.2, 95% CI ?17 to ?1.4, P=0.02) and on physician global
assessment (coefficient ?8, 95% CI ?13.6 to ?2.4, P=0.01), "suggesting
it may have symptom-modifying effects," the researchers reported in the
August issue of Rheumatology.

Methotrexate has come to be considered a standard treatment in psoriatic
arthritis, being recommended in recent guidelines, yet the drug has
never demonstrated efficacy for this condition in a randomized clinical

Because other treatments such as tumor necrosis factor inhibitors have
been proven effective in psoriatic arthritis, and because methotrexate
is not without potential toxicity, Kingsley and colleagues undertook a
blinded study to clarify the role for methotrexate in this disorder.

Beginning in 2003, they enrolled 221 patients who received methotrexate
in a target dosage of 15 mg per week or matched placebo.

The patient population was predominantly male, with a mean age of about
48 years. Disease duration was approximately 12 months.

More than 80% of participants also were taking nonsteroidal
anti-inflammatory drugs.

After 6 months of treatment, there was no significant effect seen when
overall efficacy was assessed on the American College of Rheumatology
20% improvement criteria (OR 2.0, 95% CI 0.65 to 6.22) or on the disease
activity score in 28 joints (OR 1.70, 95% CI 0.90 to 3.17), the
researchers reported.

A minimum odds ratio showing efficacy would be 2.7, they explained.

Objective individual outcome measures were also evaluated, and no
significant effects were seen for tender and swollen joint counts, pain,
functional status, erythrocyte sedimentation rate, or C-reactive

The researchers also analyzed the data according to whether patients had
oligoarticular or polyarticular disease, and found no difference
(P=0.574 for interaction).
Skin involvement, as measured on the psoriatic arthritis skin score,
decreased in both treatment and control groups, declining in the
methotrexate group to 2.2 (95% CI 1.62 to 2.82) and to 3.13 (95% CI 2.34
to 3.92) in the placebo group.

After adjustment for age, sex, duration of disease, and baseline skin
score, a beneficial effect for the cutaneous component of the disease
was seen, with a treatment difference of ?0.93 (95% CI ?1.71 to ?0.15,
P=0.02), the researchers found.

A total of nine patients receiving methotrexate withdrew from the study
because of adverse events, as did seven on placebo.

Nausea and vomiting were reported by more than twice as many patients on
methotrexate (38 versus 16), while liver function test abnormalities
were seen in 12 methotrexate patients and in two placebo patients.

The researchers concluded that, despite some symptomatic and cutaneous
benefits, their finding of a lack of effect for synovitis means
methotrexate can't be considered to have "a true disease-modifying
effect" in psoriatic arthritis.

Other treatments actually have been found to have disease-modifying
effects in clinical trials, such as leflunomide (Arava), which had an
odds ratio of 3.4 for benefit, and etanercept (Enbrel), with an odds
ratio above 20.

The researchers conceded that their trial may have not been sufficiently
large to detect small improvements, but did not believe further study
would be needed.

"We believe a larger trial would not only be impractical but also would
be unwarranted in the face of more effective alternatives," they stated.

"We also think that guidelines for treating [psoriatic arthritis] need
to be revisited so that the sequencing of conventional drugs before
biologics are used is reevaluated," they added.

They noted that certain questions have yet to be answered, such as
whether methotrexate could be used in combination with biologics or
other disease-modifying drugs in psoriatic arthritis, and whether there
are patterns of disease that might tend to show a better response.

The study was supported by Arthritis Research UK, the National Institute
for Health Research, and the UK Medical Research Council.

One co-author has received support from Abbott Laboratories and Pfizer.
Primary source: Rheumatology
Source reference:

Kingsley G, et al "A randomized placebo-controlled trial of methotrexate
in psoriatic arthritis" Rheumatology 2012; 51: 1368-1377.

Donna G.

1) Rejoice always, Pray continually, Give thanks in all circumstances,
For this is God's will for you in Christ Jesus. ( I Thessalonians
5:16-18 NIV )

2) ANGELS EXIST, but some times, since they don't all have wings, we
call them FRIENDS......

3) Just because you're in pain, doesn't mean you have to be one!