What can I take instead of Humira?

In this article:

• Compare Humira alternatives
• Methotrexate
• Remicade
• Orencia
• Rituxan
• Xeljanz
• Natural alternatives
• How to switch meds

In this article

• Compare Humira alternatives
• Methotrexate
• Remicade
• Orencia
• Rituxan
• Xeljanz
• Natural alternatives
• How to switch meds

Humira (adalimumab) is a member of the drug class known as Tumor Necrosis Factor (TNF) inhibitors. TNF is a naturally occurring cytokine and plays an important role in many inflammatory medical conditions. Excess TNF release is associated with inflammation and tissue damage. Medications which inhibit TNF are effective anti-inflammatory drugs in conditions like rheumatoid arthritis (RA), ulcerative colitis (UC), Crohn’s Disease (CD), ankylosing spondylitis, hidradenitis suppurativa, plaque psoriasis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, and uveitis. While TNF inhibitors hold many Food and Drug Administration (FDA) approved indications, they may be used off-label in some medical conditions, including graft versus host disease, sarcoidosis, and pyoderma gangrenosum. This medication is administered by a subcutaneous injection, and can be self-administered in one’s own home. 

Conversely, TNF release is not always harmful; it is released from immune cells after exposure to infectious stimuli and is therefore important in our body’s response to infection. TNF inhibitor therapy can therefore be immunosuppressive and lead to serious infections and lymphoproliferative disorders, including lymphoma. Patients will need to be tested for latent tuberculosis and hepatitis B virus before initiation of therapy and during therapy. 

What can I take in place of Humira?

TNF inhibitors are more broadly part of a category known as biologic drugs. TNF inhibitors include 2 other monoclonal antibodies besides Humira (adalimumab) – Remicade (infliximab) and Simponi (golimumab). The class also includes a polyethylene glycol-conjugated fab fragment under the brand name Cemzia (certolizumab), and a fusion protein under the brand name Enbrel (etanercept). Humira was the first human monoclonal antibody FDA approved for rheumatoid arthritis in 2003, and since has picked up many additional FDA-approved indications. 

Abbvie’s patent for Humira expired in 2023 and several Humira biosimilars have become available for patients, which is monumental as the main difference will be reduced drug pricing. Biosimilars are defined as an FDA-approved biopharmaceutical that is similar but not identical to its reference product, and a subset may also be granted an additional FDA-approved interchangeable label. To date, there are 10 biosimilars of adalimumab FDA-approved, but only 3 have been approved as an interchangeable product – Abrilada (adalimumab-afzb; Pfizer), Cyltezo (adalimumab-adbm; Boehringer Ingelheim), and Simlandi (adalimumab-ryvk; Teva). The others include Amjevita (adalimumab-atto; AmGen), Hadlima (adalimumab-bwwd; Organon), Hulio (adalimumab-fkjp; Biocon Biologics Inc), Hyrimoz (adalimumab-adaz; Sandoz), Idacio (adalimumab-aacf; Fresenius Kabi), Yuflyma (adalimumab-aaty; Celltrion), and Yusimry (adalimumab-aqvb; Coherus BioSciences). Even for the 3 Humira biosimilars considered interchangeable, there are some key features of each that pharmacists and prescribers should become familiar with-including factors like presence of latex, to which many have allergies, differences in administration, and concentrations. Formularies of pharmacy benefit managers (PBMs) are undergoing modifications based on adalimumab biosimilar availability, which can add to confusion and frustration. 

RELATED: Cyltezo vs. Humira

Other biologic medications with different mechanisms of action and efficacy against similar medical conditions also exist, generally with inhibitory activity against a different set of cytokines from TNF in our immune system called interleukins. These biologic drugs may also serve as alternatives to Humira (adalimumab). Traditional medications used to manage some of these conditions, known as disease-modifying antirheumatic drugs, or DMARDs, are used often and early in the diagnosis specifically of rheumatoid arthritis and include medications like methotrexate. In this article we will discuss alternative drugs to Humira as treatment options for some of these autoimmune conditions and reasons why they may be sought out by individuals. 

Other alternatives to Humira

• Kevzara (sarilimumab)
• Actemra (tocilizumab)
• Kineret (anakinra)
• Imuran (azathioprine)
• Neoral (cyclosporine)
• Plaquinil (hydroxychloroquine)
• Arava (leflunomide)
• Azulfidine (sulfasalazine)
• Olumiant (baricitinib)
• Rinvoq (upadacitinib)
• Benlysta (belimumab)
• Taltz (ixekizumab)

Top 5 Humira alternatives

Methotrexate

Oral methotrexate is traditionally the first line DMARD selected for patients with rheumatoid arthritis (RA), and if there is an inadequate response after three to four months of optimized methotrexate dosing, a different DMARD may be tried or added, a biologic agent (like adalimumab) or even medications in other drug classes may be added to the regimen. The exact mechanism of action of DMARDs are unknown but are believed to decrease tissue damage by suppressing toxic compounds or their metabolites which damage tissues. 

The benefit of methotrexate as a first-line agent is not only its demonstrated efficacy, but also it is very cost effective (~$30 per month) in comparison to biologic medications like adalimumab. Unfortunately, it comes along with several side effects which may be intolerable to some individuals to continue the medication, including liver toxicity and immunosuppression. Patients on methotrexate require close laboratory monitoring when therapy is initiated, which can be spaced out the longer a patient is on the medication (up to a minimum frequency of every 3 months). 

Methotrexate can cause GI side effects including nausea, vomiting, and diarrhea – some of these side effects may be alleviated by splitting the once-weekly dose into two or three doses given 12 hours apart. Methotrexate should not be used in patients with poor renal function at baseline. 

Remicade (infliximab)

Like Humira (adalimumab), Remicade (infliximab) is a monoclonal antibody with activity against TNF. It would be considered an add-on therapy to methotrexate for rheumatoid arthritis, but is also indicated for many other inflammatory conditions like Crohn’s Disease and psoriatic arthritis. Unlike Humira (adalimumab), Remicade is not self-injectable – it requires an intravenous infusion in a monitored setting. Remicade may cause acute infusion reactions including fever, chills, and skin reactions, which can happen at an increased risk if doses are skipped. It can be given much less frequently than Humira (adalimumab) since its dosing schedule is typically every four to eight weeks (versus every two weeks). Other common side effects are faimilar to Humira. 

RELATED: Remicade vs. Humira: Which is better for you

Orencia (abatacept)

Orencia (abatacept) is in a different drug class from Humira, known as T-cell costimulation modulators; it inhibits T-cell (a component of our immune system) activation found in the synovium of patients with rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and psoriatic arthritis. 

Orencia (abatacept) can be administered either as flat-dose subcutaneous injection or a weight-based intravenous infusion. This medication interacts with many other medications, so a review of other medications a patient is taking should be reviewed before its initiation. While in the setting of rheumatoid arthritis, Orencia can be added to traditional DMARDs for optimal management of rheumatoid arthritis, but it should not generally be added to a regimen already including a TNF–inhibitor like Humira since it can also cause serious and potentially fatal infections and this risk would be additive. 

Rituxan (rituximab)

Rituxan (rituximab) is type of monoclonal antibody that comprises yet another medication class used in the management of these inflammatory conditions, known as a B lymphocyte-depleting agent. In rheumatoid arthritis, B cells are believed to play a role in its development and progression, so offers management by a different mechanism. 

Rituxan should not be used in patients with severe active infections, and patients will need to be screened for hepatitis B virus prior to initiating therapy. Patients receiving Rituxan will likely receive antimicrobial prophylaxis against opportunistic infections and/or viral reactivation during therapy and for up to 12 months after therapy completion. It is administered in a setting requiring medical observation by IV infusion, and given its side effect of infusion related reactions, patients will often receive premedication to prevent these reactions 30 minutes prior to the initiation of the infusion. 

Xeljanz (tofacitinib)

Xeljanz (tofacitinib) is in a medication class known as Janus Kinase Inhibitors, and works by inhibiting the JAK enzyme which plays a role in cytokine signaling linked to joint and tissue inflammation. 

Xeljanz is an oral tablet taken twice daily, which is an advantage over many of the other medications discussed. Monitoring is required throughout therapy, including a lipid profile at baseline, after 4 to 8 weeks, and then every 6 months. In addition, a patient’s lymphocytes and neutrophils should be monitored at baseline, after 4 to 8 weeks, and then every 3 months. Liver function tests and renal function should also be routinely monitored. 

Dose modifications or holding Xeljanz completely may be recommended by any changes observed with this monitoring. Like all the medications discussed, Xeljanz also comes with the potential of causing serious side effects. For example, clinical trials have demonstrated that the higher dose of 10mg twice daily demonstrated higher risk of all-cause mortality (including sudden cardiovascular death) and thrombosis in rheumatoid arthritis patients greater than 50 years of age with at least one cardiovascular risk factor compared to the lower dose of 5mg twice daily or a TNF blocker like Humira. Thrombosis has also been reported with JAK inhibitors, and they are immunosuppressants so appropriate screening must be completed prior to initiation. 

Natural alternatives to Humira

Complementary approaches to manage the conditions Humira treats should be considered supplemental to the medications discussed. Probiotics and prebiotics may be helpful in management of Crohn’s disease and ulcerative colitis, as well as drinking aloe vera. Certain micronutrient deficiencies may be common in these inflammatory bowel diseases, including iron, B12, vitamin D, vitamin K, folic acid, selenium, zinc, vitamin B6, and vitamin B1. Anti-inflammatory supplements may also be helpful, including fish oil, cayenne pepper, and turmeric. Adopting healthy lifestyle practices is important to minimize risk for infections when taking immunosuppressing medications. 

RELATED: The best natural remedies for arthritis | The 6 best exercises for arthritis

How to switch to a Humira alternative

With the introduction of biosimilars and particularly interchangeable biosimilars to the market, be aware of state laws related to substitution and that prescriber notification is not always required. Formularies of payors may be modified to preferably cover one of the interchangeable biosimilars for prescriptions of Humira, and clear communication with patients of these interchanges is critical. For example, if a payor requires a Humira prescription be interchanged to Cyltezo. In that case, it is important for patients to be counseled that the volume to inject with Cyltezo may be twice as much as they are accustomed unless the newly approved high concentration formulation is interchanged. Differences in administration techniques, storage, and indications may vary between products. 

It is important to seek medical advice from a trusted healthcare provider regarding abrupt discontinuation or plan to switch therapies. Stopping a biologic drug may cause the body to develop antibodies against it, so if it is resumed it will lose its efficacy. Similarly, withdrawal has been reported with the abrupt discontinuation of biologic drugs. Often, the conditions Humira and its alternatives treat are chronic conditions and will require life-long therapy of some kind.

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