Methotrexate for Joint Pain
Recruiting in Palo Alto (17 mi)
Overseen byMichael Kolinsky
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: AHS Cancer Control Alberta
Must be taking: Hydroxychloroquine, Prednisone
Must not be taking: Immunosuppressives, Corticosteroids
Disqualifiers: Rheumatoid arthritis, Lupus, Cardiovascular, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?Many people develop joint pain, stiffness and swelling due to their cancer treatment that targets the immune system.
The severity of symptoms ranges from mild to debilitating and sometimes requires delaying or stopping cancer treatment.
The usual plan is to discontinue cancer treatment and give relatively high doses of a medication called prednisone (a steroid, which is an anti-inflammatory medication which may suppress the immune system), with a gradual lowering of the dose over several weeks.
While this can be effective, prednisone can cause several side effects, and it is not known if this is the best or safest treatment.
Hydroxychloroquine is a medication being studied on IMPACT 2.0 on participants who develop inflammatory joint pain while taking cancer treatments that affect their immune system. It is possible that the hydroxychloroquine treatment may not work well on some participants on IMPACT 2.0. Hydroxychloroquine is also given as standard of care to participants with this type of inflammatory joint pain.
The goal of this study is to learn how well methotrexate is at treating inflammatory joint pain in participants from IMPACT 2.0 that don't do well on treatment with hydroxychloroquine and in patients given hydroxychloroquine as standard of care to treat this type of inflammatory joint pain caused by taking cancer treatments which target their immune system.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it allows the use of prednisone and hydroxychloroquine as part of the study or standard care. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug methotrexate for joint pain?
Methotrexate has been shown to help reduce joint pain and inflammation in people with rheumatoid arthritis, with studies indicating improvements in pain and joint swelling compared to those not taking the drug. However, the benefits may decrease over time, and some people may experience side effects.
12345Is methotrexate generally safe for humans?
Methotrexate is generally considered safe and well-tolerated for treating rheumatic diseases, but it can have side effects like mild liver issues and rare serious conditions like pancytopenia (a drop in blood cells). It should be used with caution, especially in people taking other medications, and requires regular monitoring.
16789How does the drug methotrexate differ from other treatments for joint pain?
Methotrexate is unique for joint pain treatment because it targets synovitis (inflammation of the joint lining), which is common in osteoarthritis and associated with pain. Unlike other treatments, it has a well-established safety profile and is already a gold standard for inflammatory conditions like rheumatoid arthritis, making it a promising option for reducing pain in osteoarthritis.
810111213Eligibility Criteria
This trial is for adults with cancer who developed arthritis or joint pain from immune-targeting cancer treatments. They must have tried hydroxychloroquine without success, or still need steroids after 3 months. Participants should be over 18, able to consent, and have a decent performance status (ECOG 0-2). Their kidneys must function well, blood counts within normal ranges, and liver tests normal.Inclusion Criteria
I am 18 years old or older.
I am able to understand and agree to the study's requirements.
My kidney function, measured by creatinine levels or clearance, is within normal range.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive Methotrexate 20 mg PO weekly for 12 weeks, with folic acid 1mg PO daily and prednisone starting at 20 mg PO daily for 8 weeks tapering dose
12 weeks
Weekly visits for methotrexate administration
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessments of cytokine profiles, immunophenotyping, and musculoskeletal ultrasound
4 weeks
2 visits (in-person)
Long-term follow-up
Participants are monitored for progression-free survival and other long-term outcomes
3 years
Participant Groups
The IMPACT 2.1 study is testing methotrexate as a treatment for inflammatory joint pain in patients who didn't respond well to hydroxychloroquine or are on long-term steroids due to side effects from certain cancer immunotherapies.
1Treatment groups
Experimental Treatment
Group I: Single ArmExperimental Treatment1 Intervention
Methotrexate 20 mg PO weekly for 12 weeks.
Folic acid 1mg PO daily for as long as Methotrexate is given.
Prednisone starting at 20 mg PO daily for 8 weeks tapering dose.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cross Cancer InstituteEdmonton, Canada
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Who Is Running the Clinical Trial?
AHS Cancer Control AlbertaLead Sponsor
References
Methotrexate in rheumatoid arthritis. Indications, contraindications, efficacy, and safety. [2019]Evidence on the safety and efficacy of methotrexate as a second- or third-line agent for treating patients with rheumatoid arthritis is reviewed. Four placebo-controlled clinical trials have documented short-term benefit from methotrexate; although true remission is rare, patients receiving methotrexate showed a 26% (95% confidence interval [CI], 17% to 35%) greater improvement in their inflamed joint count and a 39% (95% CI, 26% to 51.5%) greater improvement in pain than did controls receiving nonsteroidal anti-inflammatory agents with or without prednisone. With respect to long-term benefit, improvement usually occurs within 1 month, reaching a maximum at 6 and then leveling off for the duration of treatment; in some patients, the benefit may wane after an initial satisfactory response in the first 4 to 6 months. In one third of those given methotrexate, treatment had to be discontinued because of adverse effects, less than 1% of which were life threatening. Careful baseline and follow-up monitoring is recommended until more data on the safety of methotrexate are available.
Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. [2022]To determine whether patients with undifferentiated arthritis (UA; inflammatory, nontraumatic arthritis that cannot be diagnosed using current classification criteria) benefit from treatment with methotrexate (MTX).
Patient-reported health outcomes in a trial of etanercept monotherapy versus combination therapy with etanercept and methotrexate for rheumatoid arthritis: the ADORE trial. [2022]This study assessed the relative efficacy of etanercept (ETN) or etanercept and methotrexate (ETN+MTX) for patients with rheumatoid arthritis (RA) who had an unsatisfactory response to MTX, using patient-reported outcomes (PROs) of function, pain, general health, disease activity and morning stiffness.
Severe flare of rheumatoid arthritis after discontinuation of long-term methotrexate therapy. Double-blind study. [2022]To determine if long-term methotrexate-induced improvement of rheumatoid arthritis is sustained after the drug is discontinued, 10 unselected patients with responses to weekly oral methotrexate given for at least 36 months (mean 40.1) were randomly assigned to receive methotrexate or identical-appearing placebo tablets for two months. After one month, all five patients receiving placebo had to have the study terminated due to a flare of their disease manifested by statistically significant deterioration in multiple clinical parameters. It is concluded that patients receiving long-term methotrexate must continue the drug to maintain clinical benefits.
Efficacy of low-dose methotrexate in rheumatoid arthritis. [2022]Twenty-eight patients with refractory rheumatoid arthritis completed a randomized 24-week double-blind crossover trial comparing oral methotrexate (2.5 to 5 mg every 12 hours for three doses weekly) with placebo. The methotrexate group had significant reductions (P less than 0.01 as compared with the placebo group) in the number of tender or painful joints, the duration of morning stiffness, and disease activity according to physician and patient assessments at the 12-week crossover visit; reductions in the number of swollen joints (P less than 0.05) and 15-m walking time (P less than 0.03) also occurred. These variables, as well as the grip strength and erythrocyte sedimentation rate, showed significant (P less than 0.01) improvement at 24 weeks in the population crossed over to methotrexate. A significantly increased frequency (P less than 0.03) of the HLA-DR2 haplotype occurred in the eight patients with the most substantial response to methotrexate. Adverse reactions during methotrexate therapy included transaminase elevation (21 per cent), nausea (18 per cent), and diarrhea (12 per cent); one patient was withdrawn from the trial because of diarrhea. One patient died while receiving the placebo. Methotrexate did not affect measures of humoral or cellular immunity. We conclude that this trial provides evidence of the short-term efficacy of methotrexate in rheumatoid arthritis, but the mechanism of action is unknown. Longer trials will be required to determine the ultimate safety and effectiveness of this drug.
[Methotrexate toxicity. Myths and facts]. [2021]Methotrexate (MTX) is a safe and well-tolerated drug for the treatment of rheumatic diseases, even if the strictest safety standards are considered. Initial apprehension as to severe pulmonary or hepatic side-effects has not been confirmed. The risk of infection is not elevated compared with other disease-modifying antirheumatic drugs. In addition, a mutagenic potential could not be demonstrated even after long-term application. Therefore, MTX will maintain its significant role in antirheumatic therapy also in the near future.
[Pancytopenia during low-dosage methotrexate treatment in patients with rheumatoid arthritis]. [2013]Adverse effects are no more common during treatment with low doses of methotrexate than during treatment with conventional anti-rheumatic drugs. Serious events do occur, however, and among the most dangerous is pancytopenia. We describe five patients with this complication. Triggering factors for such adverse events are often interactions with other medication, especially drugs that reduce renal clearance of methotrexate, and also other anti-folate drugs, e.g. trimetoprim. Events that increase the rate of cell formation in the myelopoietic tissue, e.g. infection and haemorrhage, may also increase risk of complications. Use of leukovorin is recommended when bone marrow suppression is suspected.
[Methotrexate in rheumatoid arthritis]. [2013]Methotrexate may be effective in patients with rheumatoid arthritis refractory to other treatments (gold salts, d-penicillamine and antimalarial drugs). Success rates from 39 to 88% have been reported. The mechanism of action is unknown, but is supposedly related to anti-inflammatory and immunosuppressive effects. Frequent side effects are observed on prolonged treatment. Most of these are mild and disappear with dose reduction. An exception is pneumonitis, a hypersensitivity reaction that may appear early and at low doses. Hepatotoxic effects are milder than those observed in patients with psoriasis. Intraarticular administration is not effective. No carcinogenic effects have been observed in humans. The drug should be administered with caution in fertile males and females due to possible teratogenic effects. New studies involving larger number of patients may help establish a significant role for methotrexate in the treatment of rheumatoid arthritis.
[Pancytopenia after methotrexate treatment]. [2013]The use of methotrexate is associated with the risk of numerous, sometimes life-threatening, side effects. We describe a 76-year-old female patient treated with methotrexate (MTX) due to vertebral joint disease of unknown etiology. During the outpatient therapy, which was not conformed to doctor's recommendations, acute liver failure and symptoms of bone marrow damage developed. Despite intensive hospital treatment, the patient died.
Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase iii trial of treatment effectiveness (PROMOTE): study protocol for a randomized controlled trial. [2022]Osteoarthritis (OA) is the fastest growing cause of disability worldwide. Current treatments for OA are severely limited and a large proportion of people with OA live in constant, debilitating pain. There is therefore an urgent need for novel treatments to reduce pain. Synovitis is highly prevalent in OA and is associated with pain. In inflammatory arthritides such as rheumatoid arthritis, methotrexate (MTX) is the gold standard treatment for synovitis and has a well-known, acceptable toxicity profile. We propose that using MTX to treat patients with symptomatic knee OA will be a practical and safe treatment to reduce synovitis and, consequently, pain.
[Non-cancer uses of methotrexate]. [2017]Methotrexate, used for nearly 40 years as an antimetabolite for cancer therapy, also has indications in dermatology, rheumatology and pneumology. When given at low dosage, it has an antiinflammatory effect although the mechanism is not totally understood. Numerous therapeutic trials have been performed in chronic inflammatory diseases such as rheumatoid arthritis in the adult, juvenile polyarthritis and corticosteroid-dependent asthma. Methotrexate is effective in severe resistant forms of rheumatoid arthritis and is used either alone or in combination with other drugs as first intention therapy because of the good tolerance, patient compliance and ease of use. The beneficial effect in severe corticosteroid-dependent asthma remains to be demonstrated. It has also been used in severe forms of psoriasis and may be useful in other diseases with an autoimmune component. Other less common indications including Crohn's disease, ectopic pregnancy and pregnancy termination require confirmation. Tolerance and compliance are generally good, even for prolonged treatments and undesirable effects are almost always reversible at withdrawal.
Rheumatoid arthritis: choice of antirheumatic treatment. Methotrexate first. [2015]Various drugs with different risk-benefit balances are claimed to reduce the intensity and frequency of exacerbations and to slow the progression of rheumatoid arthritis. What is the basis for choosing the most appropriate treatment for a given patient? Methotrexate is the best-assessed antirheumatic drug, and the one with which we have the most experience. At doses of 7.5 mg to 25 mg per week, methotrexate relieves pain, reduces the number of affected joints, and provides a functional improvement. It has the adverse effects common to all immunosuppressants, particularly gastrointestinal and haematological disorders. Treatment withdrawals due to adverse effects are infrequent at the doses used in rheumatoid arthritis. Other synthetic antirheumatic drugs such as azathioprine, chloroquine and its derivatives, ciclosporin, cyclophosphamide, D-penicillamine, leflunomide, gold salts and sulfasalazine are no more effective than methotrexate. Some are less effective, and others are more toxic. When used as monotherapy in clinical trials, TNF-alpha antagonists (etanercept and adalimumab) were no more effective than methotrexate on clinical outcome after one or two years. Etanercept and adalimumab seem to have similar risk-benefit balances. In about 10 comparative trials, combination of methotrexate and a TNF-alpha antagonist was more effective than methotrexate monotherapy on functional status and symptoms, especially in initially severe rheumatoid arthritis. Although it has not been proven, the risk of severe adverse effects is likely to be higher with such combinations, and follow-up in comparative trials does not exceed two years. The use of TNF-alpha antagonists is also less convenient, as weekly injections or monthly infusions are necessary. There is no firm evidence that other combinations of antirheumatic drugs are more effective than TNF-alpha antagonist-methotrexate combinations. In patients in whom TNF-alpha antagonists had failed, a combination of rituximab and methotrexate was more effective than methotrexate alone. There is no firm evidence that tocilizumab (an interleukin inhibitor) or abatacept (a drug acting on T lymphocytes) has a better risk-benefit balance than rituximab. The symptomatic efficacy of long-term corticosteroid therapy lasts at least three months but usually less than a year. Efficacy in patients in whom other treatments have failed is uncertain. There is no evidence that introducing methotrexate soon after diagnosis, alone or in combination with a TNF-alpha antagonist, slows the progression of rheumatoid arthritis. In practice, methotrexate is the first-line antirheumatic drug. If methotrexate monotherapy is ineffective, or when rheumatoid arthritis is initially severe, adding a TNF-alpha antagonist can be beneficial. A third-line option is to combine rituximab with methotrexate.
The role of methotrexate in psoriatic arthritis: what is the evidence? [2017]Methotrexate is a popular and widely used medication for the treatment of psoriatic arthritis. Herein we review the body of evidence for its use and examine its benefits as well as its limitations, both as a monotherapy and in combination with other DMARDs and biological drugs.