Re: Incidence and Risk Factors for Methotrexate-induced Pulmonary Disease during Treatment of Rheumatoid Arthritis

[Guest guest]

a,

You've posted two very interesting studies, (use of opiates) and this one.

Thanks for the information. It's nice to know that in studies MTX

complications are relatively rare.

I don't know if I mentioned that when I had an ortho look at my right

shoulder, we discussed some of my lab results. I was telling him that my

C-Reactive Protein varied from 13 to 31, seeming to have settled, for the

last two tests which coincide with my last two rheumy appointments, at 24.

He shouted, " that's off the charts! " I suspected that, but I don't know why

it doesn't go down. Certainly, the MTX and Vioxx have relieved most of my

symptoms, but I remain concerned that the C-Reactive Protein continues to

indicate a significant inflammatory process is going on.

Is there anyone else in the group with a similar experience?

Thanks,

Suzanne

[ ] Incidence and Risk Factors for Methotrexate-induced

Pulmonary Disease during Treatment of Rheumatoid Arthritis

Incidence and Risk Factors for Methotrexate-induced Pulmonary Disease during

Treatment of Rheumatoid Arthritis

Category: 17 RA Grant W Cannon1, C Cerveny1, Barbara K Finck2,

M Simpson3,

Vibeke Strand4

1VA and University of Utah, Salt Lake City, UT;2Immunex, Seattle,

WA;3Aventis, Bridgewater, NJ;4Stanford University, Palo Alto, CA

Presentation Number: 355

Poster Board Number: 355

Keywords: Methotrexate, Lung disease, Risk factors

Purpose: A previous analysis of prospective data from large prospective

randomized controlled clinical trials in rheumatoid arthritis (RA) employing

methotrexate (MTX) control groups determined the prevalence of MTX-induced

pulmonary disease as 1% during the first two years of treatment with MTX on

an intent-to-treat analysis (Arthritis Rheum: 43(Suppl):S341, 2000). These

data have been further analyzed to determine the incidence of MTX ­induced

pulmonary disease during each of the first two years of treatment and to

identify potential risk factors for its development.

Methods: These studies compared leflunomide (LEF), etanercept (ETN), and

placebo (PLC) with MTX. Initial patient enrollment in these prospective

study protocols were: MTX (n=182) vs LEF (n=182) vs PLC (n=118); MTX (n=498)

vs LEF (n=501); and MTX (n=217) vs ETN (n=415) for a total of 897 patients

initially treated with MTX in this cohort.

Results: During the first year (763 patient-years MTX exposure) and during

the second year (353 patient-years MTX exposure), seven cases (incidence

rate = 0.92 cases/100 patient-years) and two cases (incidence rate = 0.57

cases/100 patient-years) MTX-induced pulmonary disease respectively were

identified.

As we previously reported, the mean age of subjects who eventually developed

MTX induced pulmonary toxicity (66±7 years) was greater than the mean age of

subjects without MTX-induced pulmonary toxicity (54±12) (p<0.001).

Evaluation of other potential risk factors included an analysis of

additional demographic factors (gender, duration of RA, seropositive

status), baseline measurements of RA disease activity (joint tenderness

count, joint swelling count, patient global assessment, physician global

assessment, morning stiffness, and disability scores), the use of concurrent

folate supplementation, laboratory parameters (including acute phase

reactants, serum albumin), smoking history, and history of underlying lung

disease. None of these potential risk factors at baseline were statistically

significantly different in subjects with MTX-induced pulmonary disease in

comparison to subjects without MTX-induced pulmonary disease. Because

patients with poorly controlled diabetes (LEF studies) and insulin dependent

diabetes (ETN study) were excluded and/or limited in enrollment in these

trials it is impossible to comment on the potential for diabetes as risk

factor for MTX-induced pulmonary disease using these data.

Conclusions: Treatment of RA with MTX is associated with the development of

MTX-induced pulmonary disease. The incidence of this serious complication

appears to be more common during the first year of treatment. Other than

increased age, no significant additional risk factors were identified.