When we think about family planning issues among patients with rheumatic disease, most of us initially think about our female patients, and for good reason. These are our patients who provide challenges during preconception planning, pregnancy itself, and postpartum. There is a lot to discuss with these patients, and many ups and downs to navigate along the way.

It’s easy to therefore forget that our male patients sometimes also need our help and guidance to help build their happy families.

A few years ago, I had a patient, Joe, who presented to my office in his early 30s. He was initially accompanied by his 28-year-old wife and their 9-month old son. Joe complained of bilateral hip pain, as well as left ankle and heel pain, that had been ongoing for approximately 2-3 years.

Joe had been seeing an orthopedic surgeon for treatment but had grown increasingly frustrated with his lack of improvement. He ended up in our practice after landing in the emergency room one evening with severe left ankle pain. He was given an initial diagnosis of gout and was prescribed indomethacin 50 mg QD. This provided moderate pain relief, but he still complained of persistent daily pain when he arrived in our office.

At the time, Joe was employed as a chef in a local resort during the high tourist season, or approximately 6 months a year. This was a physically demanding profession, requiring 80 hours a week of work, almost all on his feet in a hot kitchen. Joe complained that getting through each day was getting harder and harder as his joints were deteriorating rapidly and the pain was increasing exponentially each year. During our initial conversation, Joe said he had never noticed any psoriatic skin lesions. He also said that he had never been diagnosed with inflammatory eye or inflammatory bowel disease. He had a family history of seropositive rheumatoid arthritis and psoriasis through his mother, who was still living and being treated with methotrexate and adalimumab (a tumor necrosis factor [TNF] inhibitor).

The evidence surrounding the impact of specific medications on male fertility is limited. However, studies have shown that some medications are transmitted through semen while others are not.

On physical exam, Joe had a variety of worrisome findings. These included the following:

• Reduced range of motion and severe tenderness of the bilateral hips
• Severe swelling and tenderness of the left ankle
• Tenderness, swelling, and warmth over the Achilles tendon
• Bony changes and crepitus of the right knee
• Pitting of his fingernails

Lab tests demonstrated an elevated C-reactive protein and erythrocyte sedimentation rate. Joe’s platelets were also elevated, possibly indicating long-term inflammation. Other labs, including rheumatoid factor, anti-cyclic citrullinated peptide antibody, hepatitis serologies, and QuantiFERON-TB Gold, were normal. As per the Classification Criteria for Psoriatic Arthritis (CASPAR) diagnostic metric, Joe scored 4 points, which is diagnostic for psoriatic arthritis (PsA). He “earned” points due to a family history of psoriasis (his mother had been previously diagnosed), nail pitting, a negative lab test for rheumatoid factor, and previous dactylitis.

As a young man with a wife and small child, Joe had no choice but to continue working. Relieving his overall daily pain was, therefore, a top priority in his care. His severe disease and joint erosions made this a significant challenge, and there were numerous factors to consider as we tried to come up with a sensible, realistic course of action. Joe’s wife was a teacher transitioning from one school to another and was consequently between insurance plans (as a seasonal chef, Joe was not offered health insurance through his employer). That meant we had to consider an inexpensive “bridge” option while waiting for the family’s new insurance to kick in.

While Joe and his wife said they were not planning on having another baby “right now,” they did tell me that they thought they would try for a second child within a year. This put me on an even higher level of alert, and I noted that it would be important to check in with Joe regularly to determine when this plan was going to be accelerated.

The evidence surrounding the impact of specific medications on male fertility is limited. However, studies have shown that some medications are transmitted through semen while others are not (the evidence for some medications is unclear). The product label for methotrexate (MTX), for example, recommends that men stop the medication 3 months prior to attempting pregnancy. However, the new American College of Rheumatology (ACR) guidelines for the management for reproductive health conditionally recommend continuing with MTX in men with rheumatic diseases interested in family planning, as “data show no evidence for mutagenesis or teratogenicity.”¹

At the time of Joe’s initial presentation to our practice, his wife was taking appropriate birth control, so we started him on methylprednisolone to manage his immediate flare as well as MTX 15 mg QW and folic acid 1 mg QD. A month later, Joe demonstrated a moderate response with no notable side effects, so we increased his MTX dose to 20 mg QW and switched from the oral to subcutaneous form of the drug since this is absorbed better. Once Joe’s wife’s insurance kicked in, we added adalimumab 40 mg Q2W to his regimen.

Three months later, Joe’s pain had stabilized, and he was able to get a right hip replacement. About that same time, Joe informed me that he and his wife decided they would like to have another child. This was well before the most recent ACR guidelines, so we decided to discontinue MTX immediately and advised Joe’s wife to remain on birth control for at least another 3 months so that the drug could clear from his system. We continued with adalimumab alone during this time. I spoke with Joe prior to making this change, warning him that it was possible he would see a flare in his disease. We also discussed using prednisone as a rescue drug if needed.

Based on the most recent ACR guidelines, my personal approach in male patients trying to expand their family is to consider starting or switching them to azathioprine or hydroxychloroquine. This assumes that they are not taking a TNF inhibitor as first-line therapy. As with many medication choices related to pregnancy, these are off-label uses. However, there is evidence showing that azathioprine may work as well as other nonbiologic DMARDs in the treatment of PsA when other DMARDs are not appropriate or contraindicated.² While hydroxychloroquine is not effective for the treatment of psoriasis, we have been using it clinically to help manage the swelling and pain caused by inflammation of PsA in practice for years. Use of both of these conventional DMARDs as well as TNF inhibitors are strongly recommended to continue for men with rheumatic disease who are planning to father a child.¹

What about some of the other agents we commonly use to treat PsA? Sulfasalazine does not show any teratogenic effects but may affect sperm count and quality. Personally, I am not concerned about negative effects if a couple conceives while my male patient is taking sulfasalazine. However, if I am told that planned conception is in the patient’s immediate future, I will suggest stopping sulfasalazine. Medications such as cyclosporine, leflunomide, mycophenolate mofetil, NSAIDs, COX-2 inhibitors, and rituximab are conditionally recommended to continue in male patients interested in family planning. Unfortunately, we do not have adequate reproductive data on many of our biologic and small molecule medications that are used to treat PsA so we can only use our best judgment with these.¹

Fortunately, Joe’s case had a happy ending. His disease remained under control, and he and his wife welcomed a healthy baby girl less than a year after we discontinued his MTX. Of course, once Joe’s wife became pregnant, there was no need to be worried about the drug’s effects, and we were able to restart MTX. Two years later, the family continues to do well. While Joe’s disease has been challenging to manage, he has since opened his own restaurant and is a diligent patient of ours.

When it comes to building a family, we often must err on the side of caution. Data regarding teratogenicity of many of the newer biologics used to treat rheumatic diseases is often limited, and even when we think we have a good idea regarding the best approach to take, evidence-based guidance can change (see what just happened with the MTX recommendation in men) and we have to re-evaluate our advice. It’s a careful balance to manage our patient’s pain against what is best for mom, dad, and baby, but as more information has become available, at least now we have a better roadmap to follow.

References

1. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2020;72(4):529-556.

2. Lee JC, Gladman DD, Schentag CT, Cook RJ. The long-term use of azathioprine in patients with psoriatic arthritis. J Clin Rheumatol. 2001;7(3):160-165.

AUTHOR PROFILE:
Nancy Eisenberger, MSN, APRN, FNP-C is a nurse practitioner at Arthritis, Rheumatic and Back Disease Associates in Voorhees, NJ, and a member at large on the Rheumatology Nurses Society Board of Directors.